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Despite debilitating consequences, cancer-associated malnutrition often goes under-detected due to the lack of a standardised diagnostic tool (1). The Global Leadership Initiative on Malnutrition (GLIM) criteria was established in 2018 in order to standardise the diagnosis of malnutrition globally (2). The aim of this study was to determine the association between GLIM-diagnosed malnutrition and overall survival in a large cohort of patients with mixed-cancer types. This is the first study to stratify patients according to treatment intent and is one of the largest studies to identify reduced muscle mass using gold-standard CT analysis of body composition.
Patients receiving anti-cancer treatment for solid tumours were enrolled in a cross-sectional study to examine nutritional status between 2011-2016. The GLIM criteria was retrospectively applied. CT images at the third lumbar vertebrae (L3) were used to quantify skeletal muscle index and categorised according to previously published cut-points. Survival analysis was carried out using Kaplan-Meier curves and Cox-Regression.
Of 1405 patients enrolled, 52.5% were male. Mean age was 62 years (SD:12 years). The most common cancer diagnosis was gastrointestinal (44.5%) and 60.3% had metastatic disease. In total, 40.4% of participants were diagnosed with GLIM-malnutrition (14.8% had stage 1 moderate and 25.6% had stage 2 severe malnutrition). Median follow-up time was 102.4 months (95% CI 99.6–105.2 months). Median survival for those without malnutrition was 30.4 months (95% CI 23.5–37.2 months), versus 11.0 months (95% CI 6.6 – 15.4 months p<0.001) for those with stage 1 moderate and 10.0 months (95% CI 8.1–11.9 months p<0.001) for stage 2 severe malnutrition. Multivariate-analysis (controlling for gender, age, cancer site, GLIM-malnutrition and treatment intent) demonstrated a hazard ratio (HR) of death of 1.499 (95% CI 1.233–1.822, p<0.001) for stage 1 moderate and HR 1.548 (1.322–1.800, p<0.001) for stage 2 severe-malnutrition. The prevalence of stage 2 severe malnutrition was significantly higher in the palliative cohort (receiving supportive measures) (32.7%) when compared to patients being treated with curative intent (18.2%, p=0.004).
This study is one of the largest studies to date which uses CT analysis to accurately identify reduced muscle mass and confirms that the GLIM criteria can be used to predict overall survival in a large mixed-cancer cohort. These findings suggest that malnutrition, regardless of GLIM severity ranking has a significant impact on overall survival. Future research should focus on determining oncology specific cut-points for the GLIM criteria.
We synthesize sea-level science developments, priorities and practitioner needs at the end of the 10-year World Climate Research Program Grand Challenge ’Regional Sea-Level Change and Coastal Impacts’. Sea-level science and associated climate services have progressed but are unevenly distributed. There remains deep uncertainty concerning high-end and long-term sea-level projections due to indeterminate emissions, the ice sheet response and other climate tipping points. These are priorities for sea-level science. At the same time practitioners need climate services that provide localized information including median and curated high-end sea-level projections for long-term planning, together with information to address near-term pressures, including extreme sea level-related hazards and land subsidence, which can greatly exceed current rates of climate-induced sea-level rise in some populous coastal settlements. To maximise the impact of scientific knowledge, ongoing co-production between science and practitioner communities is essential. Here we report on recent progress and ways forward for the next decade.
Unmodified and surfactant-modified clinoptilolite-rich tuff (referred to here as “clinoptilolite”) and muscovite mica were examined with tapping-mode atomic force microscopy (TMAFM) and high-resolution thermogravimetric analysis (HR-TGA) in order to elucidate patterns of hexadecyltrimethylammonium bromide (HDTMA) sorption on the treated surface and to understand the mechanisms of this sorption. TMAFM images were obtained to a scale of 50 nm by 50 nm. The images of unmodified clinoptilolite showed a framework pattern on the ac plane, comparable to previously reported images. Images of modified clinoptilolite at 12.5% and 25% of external cation exchange capacity (ECEC) coverage by HDTMA showed evidence of the HDTMA molecules arranged as elongated, topographically raised features on the ac plane. At 50% HDTMA coverage, the images contained what appeared to be agglomerations of surfactant tail groups. The z-directionthickness of the raised features on the 12.5% coverage sample corresponded to the thickness of the carbon chain of the surfactant tail-group (0.4 nm), whereas the z-thicknesson the 25% coverage sample was between 0.4 and 0.8 nm, indicating crossing or doubling of tail groups. Repulsive forces between the modified clinoptilolite and the silicon TMAFM probe increased with increasing HDTMA coverage. HR-TGA showed a 100 °C increase in HDTMA pyrolysis temperatures at coverages of less than 50%, probably due to an increased stabilization of the HDTMA due to direct tail interactions with the clinoptilolite surface at lower coverages versus smaller stabilization due to surfactant tail-tail interactions at higher coverages. Our results indicate that buildup of HDTMA admicelles or some form of a bilayer begins before full monolayer coverage is complete.
We reviewed outcomes in all 36 consecutive children <5 kg supported with the Berlin Heart pulsatile ventricular assist device at the University of Florida, comparing those with acquired heart disease (n = 8) to those with congenital heart disease (CHD) (n = 28).
Methods:
The primary outcome was mortality. The Kaplan-Meier method and log-rank tests were used to assess group differences in long-term survival after ventricular assist device insertion. T-tests using estimated survival proportions were used to compare groups at specific time points.
Results:
Of 82 patients supported with the Berlin Heart at our institution, 49 (49/82 = 59.76%) weighed <10 kg and 36 (36/82 = 43.90%) weighed <5 kg. Of 36 patients <5 kg, 26 (26/36 = 72.22%) were successfully bridged to transplantation. (The duration of support with ventricular assist device for these 36 patients <5 kg was [days]: median = 109, range = 4–305.) Eight out of 36 patients <5 kg had acquired heart disease, and all eight [8/8 = 100%] were successfully bridged to transplantation. (The duration of support with ventricular assist device for these 8 patients <5 kg with acquired heart disease was [days]: median = 50, range = 9–130.) Twenty-eight of 36 patients <5 kg had congenital heart disease. Eighteen of these 28 [64.3%] were successfully bridged to transplantation. (The duration of support with ventricular assist device for these 28 patients <5 kg with congenital heart disease was [days]: median = 136, range = 4–305.) For all 36 patients who weighed <5 kg: 1-year survival estimate after ventricular assist device insertion = 62.7% (95% confidence interval = 48.5–81.2%) and 5-year survival estimate after ventricular assist device insertion = 58.5% (95% confidence interval = 43.8–78.3%). One-year survival after ventricular assist device insertion = 87.5% (95% confidence interval = 67.3–99.9%) in acquired heart disease and 55.6% (95% confidence interval = 39.5–78.2%) in CHD, P = 0.036. Five-year survival after ventricular assist device insertion = 87.5% (95% confidence interval = 67.3–99.9%) in acquired heart disease and 48.6% (95% confidence interval = 31.6–74.8%) in CHD, P = 0.014.
Conclusion:
Pulsatile ventricular assist device facilitates bridge to transplantation in neonates and infants weighing <5 kg; however, survival after ventricular assist device insertion in these small patients is less in those with CHD in comparison to those with acquired heart disease.
We provide an overview of diagnostic stewardship with key concepts that include the diagnostic pathway and the multiple points where interventions can be implemented, strategies for interventions, the importance of multidisciplinary collaboration, and key microbiologic diagnostic tests that should be considered for diagnostic stewardship. The document focuses on microbiologic laboratory testing for adult and pediatric patients and is intended for a target audience of healthcare workers involved in diagnostic stewardship interventions and all workers affected by any step of the diagnostic pathway (ie, ordering, collecting, processing, reporting, and interpreting results of a diagnostic test). This document was developed by the Society for Healthcare Epidemiology of America Diagnostic Stewardship Taskforce.
Publication bias has the potential to adversely impact clinical decision making and patient health if alternative decisions would have been made had there been complete publication of evidence.
Methods
The objective of our analysis was to determine if earlier publication of the complete evidence on rosiglitazone’s risk of myocardial infarction (MI) would have changed clinical decision making at an earlier point in time. We tested several methods for adjustment of publication bias to assess the impact of potential time delays to identifying the MI effect. We then performed a cumulative meta-analysis (CMA) for both published studies (published-only data set) and all studies performed (comprehensive data set). We then created an adjusted data set using existing methods of adjustment for publication bias (Harbord regression, Peter’s regression, and the nonparametric trim and fill method) applied to the limited data set. Finally, we compared the time to the decision threshold for each data set using CMA.
Results
Although published-only and comprehensive data sets did not provide notably different final summary estimates [OR = 1.4 (95 percent confidence interval [CI]: .95–2.05) and 1.42 (95 percent CI: 1.03–1.97)], the comprehensive data set reached the decision threshold 36 months earlier than the published-only data set. All three adjustment methods tested did not show a differential time to decision threshold versus the published-only data set.
Conclusions
Complete access to studies capturing MI risk for rosiglitazone would have led to the evidence reaching a clinically meaningful decision threshold 3 years earlier.
The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.
Methods
Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.
Results
The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.
Conclusions
The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
We have developed the bispectral electroencephalography (BSEEG) method for detection of delirium and prediction of poor outcomes.
Aims
To improve the BSEEG method by introducing a new EEG device.
Method
In a prospective cohort study, EEG data were obtained and BSEEG scores were calculated. BSEEG scores were filtered on the basis of standard deviation (s.d.) values to exclude signals with high noise. Both non-filtered and s.d.-filtered BSEEG scores were analysed. BSEEG scores were compared with the results of three delirium screening scales: the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), the Delirium Rating Scale-Revised-98 (DRS) and the Delirium Observation Screening Scale (DOSS). Additionally, the 365-day mortalities and the length of stay (LOS) in the hospital were analysed.
Results
We enrolled 279 elderly participants and obtained 620 BSEEG recordings; 142 participants were categorised as BSEEG-positive, reflecting slower EEG activity. BSEEG scores were higher in the CAM-ICU-positive group than in the CAM-ICU-negative group. There were significant correlations between BSEEG scores and scores on the DRS and the DOSS. The mortality rate of the BSEEG-positive group was significantly higher than that of the BSEEG-negative group. The LOS of the BSEEG-positive group was longer compared with that of the BSEEG-negative group. BSEEG scores after s.d. filtering showed stronger correlations with delirium screening scores and more significant prediction of mortality.
Conclusions
We confirmed the usefulness of the BSEEG method for detection of delirium and of delirium severity, and prediction of patient outcomes with a new EEG device.
We evaluated the early impact of a new hospital-based health technology assessment (HB-HTA) program, called Smart Innovation, at the University of Washington Medical Center (UWMC).
Methods
We compared the UWMC's utilization trends for two surgical procedures to control hospitals by evaluating the difference before and after adoption decisions: (i) a new filter for transcatheter aortic valve replacement (TAVR) procedures that treat aortic valve stenosis and (ii) microwave ablation (MWA) for treating hepatocellular carcinoma. We used descriptive statistics to assess the difference between the UWMC and controls for TAVR and MWA procedures and multivariate difference-in-differences (DID) analyses to test for statistical significance.
Results
The UWMC experienced a 10 percent reduction in TAVR procedures compared with controls following the implementation of the TAVR Sentinel filter. The DID regression model indicated a 1.5 reduction in the number of TAVR procedures per quarter at the UWMC between the pre- and post period, which was not statistically significant (p-value: .87). The UWMC experienced a 51 percent reduction in utilization when compared with controls for MWA procedures in the pre- and post periods. The DID model for MWA indicated an 18.8 decrease in utilization per quarter during the study period for the UWMC, which was statistically significant (p-value: .0007). For MWA procedures, the UWMC experienced a $647,658 dollar reduction in total costs in the post period compared with controls.
Conclusions
When the UWMC used HB-HTA methods for technology adoption, there was a reduction in utilization and total costs when compared with controls; however, when the UWMC adopted a new technology without using HB-HTA methods, there was no difference in utilization.
The development of the medical student is not based solely on the acquisition of knowledge but also on development of skills and appropriate attitude. This requires ability to communicate effectively with patients and colleagues, sensitivity to patient needs, and the capability to influence patients to take the appropriate decisions and maintain behaviour change.
Recent years have seen marked changes in medical school curricula to support this and greater emphasis has also been made post Shipman.
The Faculty of Medicine and Surgery of the University of Malta has moved strongly in this direction. The Department of Psychiatry has led this and developed new courses, longitudinally throughout the curriculum.
The course in Behavioural Sciences was developed with emphasis on student-centred learning in small groups. It focuses on interpersonal communication, teamwork, reflective experience, holistic and patient-centred care, personal development and avoidance of burn out.
A vertical course in Psychology and Sociology in Relation to Health Care has also been introduced and the Course in Psychiatry has been redeveloped in accordance with recommendations of the World Federation of Medical Education and the World Psychiatric Association.
These new developments in the curriculum are described and explored.
This paper explores dependencies between operational risks and between operational risks and other risks such as market, credit and insurance risk. The paper starts by setting the regulatory context and then goes into practical aspects of operational risk dependencies. Next, methods of modelling operational risk dependencies are considered with a simulation study exploring the sensitivity of diversification benefits arising from dependency models. The following two sections consider how correlation assumptions may be set, highlighting some generic dependencies between operational risks and with non-operational risks to assist in the assessment of dependencies and correlation assumptions. Supplementary appendices provide further detail on generic dependencies as well as a case study of how business models can lead to operational risks interacting with other risks. Finally, the paper finishes with a literature review of operational risk dependency papers including correlation studies and benchmark reports.
We designed, developed, and implemented a new hospital-based health technology assessment (HB-HTA) program called Smart Innovation. Smart Innovation is a decision framework that reviews and makes technology adoption decisions. Smart Innovation was meant to replace the fragmented and complex process of procurement and adoption decisions at our institution. Because use of new medical technologies accounts for approximately 50 percent of the growth in healthcare spending, hospitals and integrated delivery systems are working to develop better processes and methods to sharpen their approach to adoption and management of high cost medical innovations.
Methods
The program has streamlined the decision-making process and added a robust evidence review for new medical technologies, aiming to balance efficiency with rigorous evidence standards. To promote system-wide adoption, the program engaged a broad representation of leaders, physicians, and administrators to gain support.
Results
To date, Smart Innovation has conducted eleven HB-HTAs and made clinician-led adoption decisions that have resulted in over $5 million dollars in cost avoidance. These are comprised of five laboratory tests, three software-assisted systems, two surgical devices, and one capital purchase.
Conclusions
Smart Innovation has achieved cost savings, avoided uncertain or low-value technologies, and assisted in the implementation of new technologies that have strong evidence. The keys to its success have been the program's collaborative and efficient decision-making systems, partnerships with clinicians, executive support, and proactive role with vendors.
To describe the relationship between adherence to distinct dietary patterns and nutrition literacy.
Design:
We identified distinct dietary patterns using principal covariates regression (PCovR) and principal components analysis (PCA) from the Diet History Questionnaire II. Nutrition literacy was assessed using the Nutrition Literacy Assessment Instrument (NLit). Cross-sectional relationships between dietary pattern adherence and global and domain-specific NLit scores were tested by multiple linear regression. Mean differences in diet pattern adherence among three predefined nutrition literacy performance categories were tested by ANOVA.
Setting:
Metropolitan Kansas City, USA.
Participants:
Adults (n 386) with at least one of four diet-related diseases.
Results:
Three diet patterns of interest were derived: a PCovR prudent pattern and PCA-derived Western and Mediterranean patterns. After controlling for age, sex, BMI, race, household income, education level and diabetes status, PCovR prudent pattern adherence positively related to global NLit score (P < 0·001, β = 0·36), indicating more intake of prudent diet foods with improved nutrition literacy. Validating the PCovR findings, PCA Western pattern adherence inversely related to global NLit (P = 0·003, β = −0·13) while PCA Mediterranean pattern positively related to global NLit (P = 0·02, β = 0·12). Using predefined cut points, those with poor nutrition literacy consumed more foods associated with the Western diet (fried foods, sugar-sweetened beverages, red meat, processed foods) while those with good nutrition literacy consumed more foods associated with prudent and Mediterranean diets (vegetables, olive oil, nuts).
Conclusions:
Nutrition literacy predicted adherence to healthy/unhealthy diet patterns. These findings warrant future research to determine if improving nutrition literacy effectively improves eating patterns.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
Methods
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Results
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Conclusions
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
Depression contributes to persistent opioid analgesic use (OAU). Treating depression may increase opioid cessation.
Aims
To determine if adherence to antidepressant medications (ADMs) v. non-adherence was associated with opioid cessation in patients with a new depression episode after >90 days of OAU.
Method
Patients with non-cancer, non-HIV pain (n = 2821), with a new episode of depression following >90 days of OAU, were eligible if they received ≥1 ADM prescription from 2002 to 2012. ADM adherence was defined as >80% of days covered. Opioid cessation was defined as ≥182 days without a prescription refill. Confounding was controlled by inverse probability of treatment weighting.
Results
In weighted data, the incidence rate of opioid cessation was significantly (P = 0.007) greater in patients who adhered v. did not adhered to taking antidepressants (57.2/1000 v. 45.0/1000 person-years). ADM adherence was significantly associated with opioid cessation (odds ratio (OR) = 1.24, 95% CI 1.05–1.46).
Conclusions
ADM adherence, compared with non-adherence, is associated with opioid cessation in non-cancer pain. Opioid taper and cessation may be more successful when depression is treated to remission.
Proficient bilinguals demonstrate slower lexical retrieval than comparable monolinguals. The present study tested predictions from two main accounts of this effect, the frequency-lag and competition hypotheses. Both make the same prediction for bilinguals but differ for trilinguals and for age differences. 200 younger or older adults who were monolingual, bilingual, or trilingual performed a picture naming task in English that included high and low frequency words. Naming times were faster for high than for low frequency words and, in line with frequency-lag, group differences were larger for low than high frequency items. However, on all other measures, bilinguals and trilinguals performed equivalently, and lexical retrieval differences between language groups did not attenuate with age, consistent with the competition view.
Race, psychiatric history, and adverse life events have all been independently associated with postpartum depression (PPD). However, the role these play together in Black and Latina women remains inadequately studied. Therefore, we performed a case–control study of PPD, including comprehensive assessments of symptoms and biomarkers, while examining the effects of genetic ancestry.
Methods
We recruited our sample (549 cases, 968 controls) at 6 weeks postpartum from obstetrical clinics in North Carolina. PPD status was determined using the MINI-plus. Psychiatric history was extracted from medical records. Participants were administered self-report instruments to assess depression (Edinburgh Postnatal Depression Scale) and adverse life events. Levels of estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanalone were assayed. Principal components from genotype data were used to estimate genetic ancestry and logistic regression was used to identify predictors of PPD.
Results
This population was racially diverse (68% Black, 13% Latina, 18% European). Genetic ancestry was not a predictor of PPD. Case status was predicted by a history of major depression (p = 4.01E-14), lifetime anxiety disorder diagnosis (p = 1.25E-34), and adverse life events (p = 6.06E-06). There were no significant differences between groups in any hormones or neurosteroids.
Conclusions
Psychiatric history and multiple exposures to adverse life events were significant predictors of PPD in a population of minority and low-income women. Genetic ancestry and hormone levels were not predictive of case status. Increased genetic vulnerability in conjunction with risk factors may predict the onset of PPD, whereas genetic ancestry does not appear predictive.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.