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Existing guidelines on overviews of reviews and umbrella reviews recommend an assessment of the certainty of evidence but provide limited guidance on how to apply GRADE to such a complex evidence synthesis. We present one approach to applying GRADE to an overview of reviews developed using general principles derived from current GRADE guidelines.
Methods
The methods were developed in an iterative and exploratory fashion following discussion with 11 methodologists and health services researchers. Key principles were distilled on the five GRADE domains (risk of bias, inconsistency, imprecision, indirectness, and publication bias) from the relevant GRADE guidelines, particularly those on test accuracy.
Results
A ‘general principles’ approach of applying the five domains of GRADE to an overview of reviews and arriving at an overall summary judgment for outcomes was developed. These methods were successfully applied to an overview of reviews on 18F-prostate specific membrane antigen positron emission tomography and computed tomography in the staging of patients with high-risk or recurrent prostate cancer.
Conclusions
Our approach distilled key principles from relevant GRADE guidelines and allowed us to apply GRADE to a complex body of evidence. Such an approach may be of interest to other researchers working on overviews of reviews or umbrella reviews.
Flowering rush (Butomus umbellatus L.) is an emergent perennial monocot that has invaded aquatic systems along the U.S.–Canadian border. Currently, there are two known cytotypes of flowering rush, diploid and triploid, within the invaded range. Although most studies have focused on the triploid cytotype, little information is known about diploid plants. Therefore, phenology and resource allocation were studied on the diploid cytotype of flowering rush in three study sites (Mentor Marsh, OH; Tonawanda Wildlife Management Area, NY; and Unity Island, NY) to understand seasonal resource allocation and environmental influences on growth, and to optimize management strategies. Samples were harvested once a month from May to November at each site from 2021 to 2023. Plant metrics were regressed to air temperature, water temperature, and water depth. Aboveground biomass peaked from July to September and comprised 50% to 70% of total biomass. Rhizome biomass peaked from September to November and comprised 40% to 50% of total biomass. Rhizome bulbil densities peaked from September to November at 3,000 to 16,000 rhizome bulbils m−2. Regression analysis resulted in strong negative relationships between rhizome starch content and air temperature (r2 = 0.52) and water temperature (r2 = 46). Other significant, though weak, relationships were found, including a positive relationship between aboveground biomass and air temperature (r2 = 0.17), a negative relationship between rhizome bulbil biomass and air temperature (r2 = 0.18) and a positive relationship between leaf density and air temperature (r2 = 0.17). Rhizomes and rhizome bulbils combined stored up to 60% of total starch, and therefore, present a unique challenge to management, as these structures cannot be reached directly with herbicides. Therefore, management should target the aboveground tissue before peak production (July) to reduce internal starch storage and aim to limit regrowth over several years.
The increased global prevalence of type II diabetes mellitus (T2DM) is associated with consumption of low fibre ‘Western diets’. Characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as low-grade systemic inflammation. Gut microbiota composition is altered significantly in these cohorts suggesting a causative link between diet, microbiota and disease. Dietary fibre consumption has been shown to alleviate these changes and improve glucose parameters in individuals with metabolic disease. We previously reported that yeast β-glucan (yeast beta-1,3/1,6-D-glucan; Wellmune) supplementation ameliorated hyperinsulinaemia and insulin resistance in a murine model. Here, we conducted a randomised, placebo-controlled, two-armed dietary fibre phase I exploratory intervention study in patients with T2DM. The primary outcome measure was alteration to microbiota composition, while the secondary outcome measures included markers of glycaemic control, inflammation as well as metabolomics. Patients were supplemented with 2·5g/day of maltodextrin (placebo) or yeast β-1,3/1,6-D-glucan (treatment). Yeast β-glucan (Wellmune) lowered insulin resistance compared with the placebo maltodextrin after 8 weeks of consumption. TNFα was significantly lower after 4 weeks of β-glucan supplementation. Significantly higher fecal concentrations of several bile acids were detected in the treatment group when compared with the placebo after 8 weeks. These included tauroursodeoxycholic acid, which was previously shown to improve glucose control and lower insulin resistance. Interestingly, the hypoglycaemic and anti-inflammatory effect of yeast β-glucan was independent of any changes in fecal microbiota composition or short-chain fatty acid levels. Our findings highlight the potential of yeast β-glucan to lower insulin resistance in patients with T2DM.
This study aimed to investigate changes in mRNA expression of the kynurenine pathway (KP) enzymes tryptophan 2, 3-dioxygenase (TDO), indoleamine 2, 3-dioxygenase 1 and 2 (IDO1, IDO2), kynurenine aminotransferase 1 and 2 (KAT1, KAT2), kynurenine monooxygenase (KMO) and kynureninase (KYNU) in medicated patients with depression (n = 74) compared to age- and sex-matched healthy controls (n = 55) and in patients with depression after electroconvulsive therapy (ECT). Associations with mood score (24-item Hamilton Depression Rating Scale, HAM-D24), plasma KP metabolites and selected glucocorticoid and inflammatory immune markers known to regulate KP enzyme expression were also explored.
Methods:
HAM-D24 was used to evaluate depression severity. Whole blood mRNA expression was assessed using quantitative real-time polymerase chain reaction.
Results:
KAT1, KYNU and IDO2 were significantly reduced in patient samples compared to control samples, though results did not survive statistical adjustment for covariates or multiple comparisons. ECT did not alter KP enzyme mRNA expression. Changes in IDO1 and KMO and change in HAM-D24 score post-ECT were negatively correlated in subgroups of patients with unipolar depression (IDO1 only), psychotic depression and ECT responders and remitters. Further exploratory correlative analyses revealed altered association patterns between KP enzyme expression, KP metabolites, NR3C1 and IL-6 in depressed patients pre- and post-ECT.
Conclusion:
Further studies are warranted to determine if KP measures have sufficient sensitivity, specificity and predictive value to be integrated into stress and immune associated biomarker panels to aid patient stratification at diagnosis and in predicting treatment response to antidepressant therapy.
Edited by
William J. Brady, University of Virginia,Mark R. Sochor, University of Virginia,Paul E. Pepe, Metropolitan EMS Medical Directors Global Alliance, Florida,John C. Maino II, Michigan International Speedway, Brooklyn,K. Sophia Dyer, Boston University Chobanian and Avedisian School of Medicine, Massachusetts
Mass gatherings and special events are commonplace in the U.S. and require the coordinated efforts of a multitude of people, including EMS, to make for a successful event. As the medical director of the EMS, it is important to understand not only the medical problems that could occur at these events but also a basic knowledge of the business behind their planning. Constant interaction with event promoters and sponsors can help the director get a feel of the safety concerns and how funding of the event will occur. These interactions can help directors determine the size, recurrence, and risks of the event providing them with the necessary information of how much manpower will be needed and the costs of the services to be provided and will give them the power to have successful negotiations with a well thought out event plan.
OBJECTIVES/GOALS: Many left hemisphere stroke survivors have a reading disorder (alexia), which is experienced as decreasing well-being. Therapies produce inconsistent results, demonstrating a need for treatment response predictors. We are investigating neural correlates of reading computational models to identify biomarkers to improve therapeutic outcomes. METHODS/STUDY POPULATION: Artificial neural network models of reading, mapping between orthography (visual word form), phonology (auditory word form), and semantics (word meaning), are trained to read single words at a healthy, adult capacity. The models are independently damaged to reflect the individual orthography-to-semantics, semantics-to-phonology, and orthography-to-phonology deficits of a sample of left hemisphere stroke survivors (n = 85). These deficits are measured with cognitive tests assessing the intactness of mappings between representations. Model damage is enacted by removing percentages of the connections between representations. For each type of deficit, the percentages of links removed are entered into a voxel-based lesion symptom mapping analysis to identify areas of cortex associated with that mapping. RESULTS/ANTICIPATED RESULTS: We anticipate that the neural correlates of model layers will be localized to a mostly left-lateralized network. Increased damage to the links between semantics and phonology in the model will likely be related to lesions involving the left posterior superior temporal sulcus and inferior frontal gyrus (IFG). Damaged orthography-to-semantic links will be related to the left fusiform gyrus (FG) and IFG. Finally, damage to the orthography-to-phonology links will be related to the left FG and superior temporal gyrus. DISCUSSION/SIGNIFICANCE: Mapping components of language models onto the brain will improve our understanding of the neural networks supporting language processing. Identifying these neural correlates may also produce biomarkers that can be used in predicting reading impairment at the acute stage or optimizing therapy in the chronic stage of stroke.
Biodesign is a relatively new interdisciplinary field, which has grown rapidly over the last decade (as evidenced for example by the growth in student teams entering the Biodesign Challenge from 9 in 2016 to 52 in 2024).
Large-scale geological structures have controlled the long-term development of the bed and thus the flow of the West Antarctic Ice Sheet (WAIS). However, complete ice cover has obscured the age and exact positions of faults and geological boundaries beneath Thwaites Glacier and Pine Island Glacier, two major WAIS outlets in the Amundsen Sea sector. Here, we characterize the only rock outcrop between these two glaciers, which was exposed by the retreat of slow-flowing coastal ice in the early 2010s to form the new Sif Island. The island comprises granite, zircon U-Pb dated to ~177–174 Ma and characterized by initial ɛNd, 87Sr/86Sr and ɛHf isotope compositions of -2.3, 0.7061 and -1.3, respectively. These characteristics resemble Thurston Island/Antarctic Peninsula crustal block rocks, strongly suggesting that the Sif Island granite belongs to this province and placing the crustal block's boundary with the Marie Byrd Land province under Thwaites Glacier or its eastern shear margin. Low-temperature thermochronological data reveal that the granite underwent rapid cooling following emplacement, rapidly cooled again at ~100–90 Ma and then remained close to the Earth's surface until present. These data help date vertical displacement across the major tectonic structure beneath Pine Island Glacier to the Late Cretaceous.
Anxiety disorders are the most frequently diagnosed psychiatric conditions in children and adolescents. Cognitive behavioural therapy (CBT) is a well-established and effective treatment for anxiety and related disorders across the lifespan. Expectations of psychotherapy have been demonstrated to affect outcomes, yet there is sparse existing literature on adolescent patient and parent perspectives of CBT prior to engagement with treatment.
Aims:
This study aimed to qualitatively explore the expectations and perceptions of CBT for anxiety and related disorders among adolescent patients and parents.
Method:
Fourteen adolescent patients and 16 parents participated in semi-structured individual interviews or focus groups consisting of 2–3 participants. Interview transcripts were analysed using inductive analysis.
Results:
Three themes were identified: worries about CBT, expectations and knowledge of the CBT process, and the role of parents and families. Overall, we found that adolescents and parents had generally positive views of CBT. The outset of CBT saw adolescents and parents express concern about stigma as well as the ambiguity of CBT. Parents continued to express a lack of understanding of what CBT entailed during their child’s treatment course.
Conclusion:
These results suggest that both adolescents and parents would benefit from early discussion and reinforcement of expectations for CBT treatment. Further research efforts are warranted and should be directed towards determining appropriate expectations for parental involvement in a child’s CBT course and effective communication of treatment expectations to both adolescents and parents.
The aim of this study was to identify and prioritize strategies for strengthening public health system resilience for pandemics, disasters, and other emergencies using a scorecard approach.
Methods:
The United Nations Public Health System Resilience Scorecard (Scorecard) was applied across 5 workshops in Slovenia, Turkey, and the United States of America. The workshops focused on participants reviewing and discussing 23 questions/indicators. A Likert type scale was used for scoring with zero being the lowest and 5 the highest. The workshop scores were analyzed and discussed by participants to prioritize areas of need and develop resilience strategies. Data from all workshops were aggregated, analyzed, and interpreted to develop priorities representative of participating locations.
Results:
Eight themes emerged representing the need for better integration of public health and disaster management systems. These include: assessing community disease burden; embedding long-term recovery groups in emergency systems; exploring mental health care needs; examining ecosystem risks; evaluating reserve funds; identifying what crisis communication strategies worked well; providing non-medical services; and reviewing resilience of existing facilities, alternate care sites, and institutions.
Conclusions:
The Scorecard is an effective tool for establishing baseline resilience and prioritizing actions. The strategies identified reflect areas in most need for investment to improve public health system resilience.
We present the third data release from the Parkes Pulsar Timing Array (PPTA) project. The release contains observations of 32 pulsars obtained using the 64-m Parkes ‘Murriyang’ radio telescope. The data span is up to 18 yr with a typical cadence of 3 weeks. This data release is formed by combining an updated version of our second data release with $\sim$3 yr of more recent data primarily obtained using an ultra-wide-bandwidth receiver system that operates between 704 and 4032 MHz. We provide calibrated pulse profiles, flux density dynamic spectra, pulse times of arrival, and initial pulsar timing models. We describe methods for processing such wide-bandwidth observations and compare this data release with our previous release.
OBJECTIVES/GOALS: Physical therapy (PT) is key for treating functional decline that inpatients experience but is a constrained resource in hospital settings. The Activity Measure Post-Acute Care (AM-PAC) score is a mobility measurement tool that has been used to define misallocation of PT. We aim to optimize PT referrals using AM-PAC-based clinical decision support . METHODS/STUDY POPULATION: We conducted a prospective study of patients admitted to University of Chicago Medical Center. AM-PAC scores were assessed by nursing staff every 12 hours. Clinical decision support was designed using validated AM-PAC cutoffs (> 18, a predictor of discharge to home). The tool was embedded in hospital medicine note templates, requiring providers to indicate PT referral status based on current AM-PAC scores. The primary outcome, unskilled consult , was defined as PT referral for patients with AM-PAC > 18. Data were collected for one year prior to implementation and one year after implementation for intervention (hospital medicine) and control (general internal medicine) services. Difference in differences analysis was used to assess the association between the intervention and unskilled consults. RESULTS/ANTICIPATED RESULTS: Between October 2018 and March 2021, 18,241 admissions were eligible for the study. Compared to preintervention, there was a lower rate of referral to PT for patients with high AM-PAC mobility scores in the post-intervention period [18.5% vs 16.6%; X2(1) = 7.02; p < 0.01]. In the postintervention time period, the control group experienced a 2.6% increase in unskilled consults while the intervention group experienced a 2.3% decrease, a difference in differences of 4.9% (95% CI -0.07–-0.03 for difference in differences) controlling for age sex, race, LOS, and change in mobility. Compared to preintervention, there was no statistically significant difference in mean change in mobility score post-intervention for either group. DISCUSSION/SIGNIFICANCE: Our results suggest that clinical decision support can decrease unskilled PT consults. Many functionally independent patients can mobilize with nursing or other mobilization staff. Hospitals should consider mobility score-based decision support to prioritize PT for impaired and at-risk patients.
An often-forgotten passage of Philip Converse's classic essay on mass belief systems introduced the concept of an issue public – a segment of voters that has crystallized attitudes about a particular topic. Some people deeply care about particular topics, and they might be equipped to reach judgments on these topics. This simple idea could provide an important corrective to work that casts citizens' political competence in a negative light. But, previous attempts to evaluate the issue publics hypothesis have been unsatisfying. This Element proposes and tests a new measurement approach for identifying issue publics. The evidence gathered leads to the conclusion that issue publics exist, but are smaller and more particularistic than existing scholarship presumes them to be. As such, researchers underappreciate the significance of issue opinions in electoral politics.
Mood problems are common after stroke, and screening is recommended. Training may support staff knowledge and implementation of screening, but the feasibility of training programmes in the Australian healthcare system has not been formally established. This study aimed to assess the feasibility of a mood screening training for a multidisciplinary team (MDT) of stroke clinicians working in a post-acute inpatient rehabilitation service.
Twelve staff from a rehabilitation service at a major hospital in Sydney, Australia participated in a 3-h interactive training session. The feasibility of running the course, assessment of knowledge gained via a consolidation exercise and quiz and acceptability of the training were assessed via focus groups.
The in-person modality of the training hindered recruitment and assessment of participants’ knowledge, though the actual measures themselves appeared appropriate. Nine participants provided feedback in two focus groups. Thematic analysis identified positive reactions to the training. However, low self-efficacy persisted and organisational/socio-cultural barriers to implementation emerged. Following training, the medical officers of the MDT had successfully implemented routine screening.
Overall, the training appeared acceptable and to foster knowledge in staff. However, limitations to recruitment and administering evaluations were identified. The development of flexible online training may improve future evaluations of screening training programmes/pathways.
Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks.
Methods
Participants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks.
Results
In primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity.
Conclusions
Response to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis.
In 2020, Baylor College of Medicine held a datathon to inform potential users of a new data warehouse, allow users to address clinical questions, identify warehouse capabilities and limitations, foster collaborations, and engage trainees. Senior faculty selected proposals based on feasibility and impact. Selectees worked with Information Technology for 2 months and presented findings. A survey of participants showed diverse levels of experience, high perceived value of the datathon, high rates of collaboration, and significant increases in knowledge. A datathon can promote familiarity with a new data warehouse, guide data warehouse improvement, and promote collaboration.
The COVID-19 pandemic has affected all our lives, not only through the infection itself but also through the measures taken to control the spread of the virus (e.g. lockdown).
Aims
Here, we investigated how the COVID-19 pandemic and unprecedented lockdown affected the mental health of young adults in England and Wales.
Method
We compared the mental health symptoms of up to 4773 twins in their mid-20s in 2018 prior to the COVID-19 pandemic (T1) and during four-wave longitudinal data collection during the pandemic in April, July and October 2020, and in March 2021 (T2–T5) using phenotypic and genetic longitudinal designs.
Results
The average changes in mental health were small to medium and mainly occurred from T1 to T2 (average Cohen d = 0.14). Despite the expectation of catastrophic effects of the pandemic on mental health, we did not observe trends in worsening mental health during the pandemic (T3–T5). Young people with pre-existing mental health problems were disproportionately affected at the beginning of the pandemic, but their increased problems largely subsided as the pandemic persisted. Twin analyses indicated that the aetiology of individual differences in mental health symptoms did not change during the lockdown (average heritability 33%); the average genetic correlation between T1 and T2–T5 was 0.95, indicating that genetic effects before the pandemic were substantially correlated with genetic effects up to a year later.
Conclusions
We conclude that on average the mental health of young adults in England and Wales has been remarkably resilient to the effects of the pandemic and associated lockdown.
This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
OBJECTIVES/GOALS: To determine if decellularized costal cartilage (DCC), which could theoretically be obtained “off the shelf,” would provide similar results to autologous cartilage grafts previously studied in this lab, thereby widening the application of our novel nipple engineering approach to all patients undergoing nipple reconstruction. METHODS/STUDY POPULATION: PLA scaffolds (diameter: 1.0 cm, height: 1.0 cm) were printed using a PRUSA 3D printer and sterilized. Lamb costal cartilage was minced (1 mm3) or zested (<0.2 mm3) and then decellularized. The quality of decellularization was assessed using DNA quantification and histological analysis. DCC was then packed into PLA scaffolds and implanted subcutaneously into immunocompetent Sprague Dawley rats using a CV flap technique. The constructs were explanted and evaluated up to 6 months after implantation. RESULTS/ANTICIPATED RESULTS: All nipple reconstructions showed well-preserved diameter and projection due to persistence of the external scaffolds at 1, 3, and 6 months. Mass and volume of engineered tissue was well-preserved over all timepoints. Compared to implantation values, engineered zested nipples demonstrated a 12% mass increase and a 22% volume increase at 6 months. Minced nipples illustrated a similar mass and volume gain with a 21% increase in mass and a 13% increase in volume at 6 months secondary to infiltration of fibrovascular tissue and growth through scaffold wall pores, respectively. Histologic analysis demonstrated a mild inflammatory infiltrate 1 month after implantation which was replaced by fibrovascular tissue by 3 months that remained stable through 6 months. The processed DCC structure remained unchanged over time. DISCUSSION/SIGNIFICANCE: Using acellular ovine xenograft within bioabsorbable scaffolds, we have engineered neonipples that maintain their volume for at least 6 months. DCC architecture is well-preserved with minimal evidence of immune-mediated degradation. By using DCC, this novel approach to nipple engineering may be applied to any patient requiring reconstruction.
Near-term risk factors for suicidal behavior, referred to as ‘warning signs’ (WS), distinguish periods of acute heightened risk from periods of lower risk within an individual. No prior published study has examined, using a controlled study design, a broad set of hypothesized WS for suicide attempt. This study addressed this gap through examination of hypothesized behavioral/experiential, cognitive, and affective WS among patients recently hospitalized following a suicide attempt.
Methods
Participants were recruited during hospitalization from five medical centers across the USA including two civilian hospitals and three Veterans Health Administration facilities (n = 349). A within-person case-crossover study design was used, where each patient served as her/his own control. WS were measured by the Timeline Follow-back for Suicide Attempts Interview and were operationalized as factors that were present (v. absent) or that increased in frequency/intensity within an individual during the 6 h preceding the suicide attempt (case period) compared to the corresponding 6 h on the day before (control period).
Results
Select WS were associated with near-term risk for suicide attempt including suicide-related communications, preparing personal affairs, drinking alcohol, experiencing a negative interpersonal event, and increases in key affective (e.g. emptiness) and cognitive (e.g. burdensomeness) responses.
Conclusions
The identification of WS for suicidal behavior can enhance risk recognition efforts by medical providers, patients, their families, and other stakeholders that can serve to inform acute risk management decisions.