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This article examines the relationships between livestock vaccinations, herd introduction decisions, and livestock disease–related outcomes. We develop a theoretical model and derive testable hypotheses about the relationships between these outcomes and practices and test them using two-stage least squares regression analysis. We find that vaccinations reduce disease-related livestock deaths, implying that vaccine availability and use may improve herd and household welfare. We do not find robust evidence of increase in disease-related illness due to herd introductions. Our results highlight the role of livestock vaccinations in safeguarding herd value, which is connected to broader household welfare for livestock keepers of Eastern Africa.
The influence of surface melt on the flow of Greenland's largest outlet glaciers remains poorly known and in situ observations are few. We use field observations to link surface meltwater forcing to glacier-wide diurnal velocity variations on East Greenland's Helheim Glacier over two summer melt seasons. We observe diurnal variations in glacier speed that peak ~6.5 h after daily maximum insolation and extend from the terminus region to the equilibrium line. Both the amplitude of the diurnal speed variation and its sensitivity to daily melt are largest at the glacier terminus and decrease up-glacier, suggesting that the magnitude of the response is controlled not only by melt input volume and temporal variability, but also by background effective pressure, which approaches zero at the terminus. Our results provide evidence that basal lubrication by meltwater drives diurnal velocity variations at Greenland's marine-terminating glaciers in a similar manner to alpine glaciers and Greenland's land-terminating outlet glaciers.
Lithium was first found to have an acute antimanic effect in 1948 with further corroboration in the early 1950s. It took some time for lithium to become the standard treatment for relapse prevention in bipolar affective disorder. In this study, our aims were to examine the factors associated wtih the likelihood of maintaining lithium levels within the recommended therapeutic range and to look at the stability of lithium levels between blood tests. We examined this relation using clinical laboratory serum lithium test requesting data collected from three large UK centres, where the approach to managing patients with bipolar disorder and ordering lithium testing varied.
46,555 lithium rest requests in 3,371 individuals over 7 years were included from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where, on subsequent testing, lithium results remained in the same category or switched category. We then examined the association between testing interval and proportion remaining within target, and the effect of age, duration of lithium therapy and testing history.
For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall 3-monthly testing was associated with 90% of lithium results remaining within range compared with 85% at 6-monthly intervals. At all test intervals, lithium test result history in the previous 12-months was associated with the proportion of next test results on target (BNF/NICE criteria), with 90% remaining within range target after 6-months if all tests in the previous 12-months were on target. Age/duration of lithium therapy had no significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) than those in the 0.40–0.79 mmolL group (2%), irrespective of testing frequency. Thus prior history in relation to stability of lithium level in the previous 12 months is a predictor of future stability of lithium level.
We propose that, for those who achieve 12-months of lithium tests within the 0.40–0.79mmol/L range, it would be reasonable to increase the interval between tests to 6 months, irrespective of age, freeing up resource to focus on those less concordant with their lithium monitoring. Where lithium level is 0.80–0.99mmol/L test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.
ABSTRACT IMPACT: This work has the potential to help clinicians decide which infants exposed to in utero opioids, will need to be treated early or can be discharged home early based on their risk, thus reducing prolonged hospitalization OBJECTIVES/GOALS: To develop and validate a prediction model with inclusion of clinical and demographic risk factors to identify infants with NAS likely to need pharmacotherapy. METHODS/STUDY POPULATION: A pooled cohort of 761 infants from 5 different studies including 2 trials and 3 observational cohorts will be used to develop the model.
All infants >than or equal to 37 weeks gestational age born to mothers with history of OUD will be included. Infants with congenital disorders and severe medical and surgical illnesses will be excluded. Multivariable mixed effects logistic regression modeling will be performed to predict the need for pharmacologic treatment for NAS. Candidate variables will be included based on clinical knowledge and previously published data. Model performance will be evaluated by measuring discrimination using Area Under the Curve (AUC) statistics and calibration. Model will be internally validated using boot strap validation. RESULTS/ANTICIPATED RESULTS: Pending data analysis DISCUSSION/SIGNIFICANCE OF FINDINGS: Opioid Use Disorder in pregnancy has resulted in concurrent rise in NAS incidence. NAS affects opioid exposed infants variably and accurate prediction of its severity and need for treatment remains elusive. Known clinical and demographic factors can predict the need for NAS therapy in opioid exposed infants, aiding clinical decision making.
Sink drains in healthcare facilities may provide an environment for antimicrobial-resistant microorganisms, including carbapenemase-producing Klebsiella pneumoniae (CPKP).
We investigated the colonization of a biofilm consortia by CPKP in a model system simulating a sink-drain P-trap. Centers for Disease Control (CDC) biofilm reactors (CBRs) were inoculated with microbial consortia originally recovered from 2 P-traps collected from separate patient rooms (designated rooms A and B) in a hospital. Biofilms were grown on stainless steel (SS) or polyvinyl chloride (PVC) coupons in autoclaved municipal drinking water (ATW) for 7 or 28 days.
Microbial communities in model systems (designated CBR-A or CBR-B) were less diverse than communities in respective P-traps A and B, and they were primarily composed of β and γ Proteobacteria, as determined using 16S rRNA community analysis. Following biofilm development CBRs were inoculated with either K. pneumoniae ST45 (ie, strain CAV1016) or K. pneumoniae ST258 KPC+ (ie, strain 258), and samples were collected over 21 days. Under most conditions tested (CBR-A: SS, 7-day biofilm; CBR-A: PVC, 28-day biofilm; CBR-B: SS, 7-day and 28-day biofilm; CBR-B: PVC, 28-day biofilm) significantly higher numbers of CAV1016 were observed compared to 258. CAV1016 showed no significant difference in quantity or persistence based on biofilm age (7 days vs 28 days) or substratum type (SS vs PVC). However, counts of 258 were significantly higher on 28-day biofilms and on SS.
These results suggest that CPKP persistence in P-trap biofilms may be strain specific or may be related to the type of P-trap material or age of the biofilm.
A Jewish priest, Roman citizen and Greek historian, Flavius Josephus (born Yosef ben Matityahu) is an author whose works are strongly marked by the confluence of traditions. Both the Jewish tradition in which he had been raised and the Graeco-Roman tradition in which he chose to write had long and varied histories of thinking about the future and Josephus, a “prophet” learned in both cultures, could draw on a variety of literary models when forecasting what was to come. Polybius, for instance, one of Josephus’ most important sources, articulates a belief in the Greek idea of cyclical history, but is able to accommodate this schema to the realities of his times by arguing that the Roman constitution had found a way to arrest the inevitable degeneration of anakyklosis. The composite Roman state had been able to postpone its decline and win extraordinary success, but nevertheless its decline would surely come some day.
Background: Antibiotic time outs (ABTOs), formal reassessments of all new antimicrobial regimens by the care team, can optimize antimicrobial regimens, reducing antimicrobial overuse and potentially improving outcomes. Implementation of ABTOs is a substantial challenge. We used quality improvement methods to implement robust, meaningful, team-driven ABTOs in general medicine ward services. Methods: We identified and engaged stakeholders to serve as champions for the quality improvement initiative. On October 1, 2018, 2 internal medicine teaching services (services A and B), began conducting ABTOs on all patients admitted to their services receiving systemic antimicrobials for at least 36 hours. Eligible patients were usually identified by the team pharmacist. ABTOs were completed within 72 hours of antibiotic initiation and were documented in the electronic medical record (EMR) by providers using a template. The process was modified as necessary in response to feedback from frontline clinicians using plan-do-study-act (PDSA) methods. We subsequently spread the project to 2 additional internal medicine services (services C and D); 2 family medicine teams (services E and F); and 1 general pediatric service (service G). The project is ongoing. We collected data for the following metrics: (1) proportion of ABTO-eligible patients with an ABTO; (2) proportion of ABTOs conducted within the recommended time frame; (3) documented plan changes as a result of ABTO (eg, change IV antibiotics to PO); (4) proportion of documented plan changes actually completed within 24 hours. Results: Within 12 weeks, services A and B were successfully completing time outs in >80% of their patients. This target was consistently reached by services C, D, E, F, and G almost immediately following launch on those services. As of June 29, 2019, >80% of eligible patients across all participating services have had a time out conducted for 16 consecutive weeks. ABTOs have resulted in a change in management in 35% of cases, including IV-to-PO change in 19% of cases and discontinuation in 5%. Overall, 77% of time outs occurred during the 36–72-hour window. Ultimately, 95% of documented plan changes were completed within 24 hours. Conclusions: ABTOs are effective but implementation is challenging. We achieved high compliance with ABTOs without using electronic reminders. Our results suggest that ABTOs were impactful in the non–critical-care general medicine setting. Next steps include (1) development of EMR-based tools to facilitate identifying eligible patients and ABTO documentation; (2) continued spread through our health care system; and (3) analysis of ABTO impact using ABTO-unexposed patients as a control group.
Life course research embraces the complexity of health and disease development, tackling the extensive interactions between genetics and environment. This interdisciplinary blueprint, or theoretical framework, offers a structure for research ideas and specifies relationships between related factors. Traditionally, methodological approaches attempt to reduce the complexity of these dynamic interactions and decompose health into component parts, ignoring the complex reciprocal interaction of factors that shape health over time. New methods that match the epistemological foundation of the life course framework are needed to fully explore adaptive, multilevel, and reciprocal interactions between individuals and their environment. The focus of this article is to (1) delineate the differences between lifespan and life course research, (2) articulate the importance of complex systems science as a methodological framework in the life course research toolbox to guide our research questions, (3) raise key questions that can be asked within the clinical and translational science domain utilizing this framework, and (4) provide recommendations for life course research implementation, charting the way forward. Recent advances in computational analytics, computer science, and data collection could be used to approximate, measure, and analyze the intertwining and dynamic nature of genetic and environmental factors involved in health development.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
The Mediterranean diet is rich in bioactive nutrients and may be effective at preventing cardiovascular disease and dementia. However, long-term sustainability could be limited in non-Mediterranean populations with different nutrient requirements and food preferences. To address this issue, our research group conducted two randomised controlled trials to examine whether the Mediterranean diet can be adapted to increase sustainability for an Australian population, while still providing cardiovascular and cognitive benefits. In our first trial (n = 41), we examined a Mediterranean diet designed to meet the calcium requirements of older adults by including 3–4 daily serves of dairy foods (milk, cheese and yoghurt) (MedDairy). In our second trial (n = 33), we tested a Mediterranean diet supplemented with 2–3 weekly serves of fresh, lean pork (MedPork), designed to provide an alternate source of protein. Both trials employed a low-fat control diet (LF) and a 24-week parallel crossover design, consisting of two 8-week intervention periods and an 8-week washout separating interventions. We found that the MedDairy intervention significantly increased dairy food (mean difference = 1.0 ± 0.2 serves, P < 0.001) and calcium intake (mean difference = 25.9 ± 6.8 mg/MJ, P < 0.001) compared to LF. Further, MedDairy led to greater improvements in morning home systolic blood pressure (mean difference = -1.6 ± 0.6 mmHg, P = 0.01), triglycerides (mean difference = -0.05 ± 0.02 mmol/L, P < 0.01), HDL (mean difference = 0.04 ± 0.01 mmol/L, P = < 0.01), and total cholesterol to HDL ratio (mean difference = -0.4 ± 0.10 mmol/L, P = < 0.001). The MedDairy intervention also led to greater improvements in processing speed (P = 0.04), a measure of cognitive function, as well as self-reported mood (P = 0.01). No significant differences were observed between MedPork and LF for blood pressure or other markers of cardiometabolic health. However, the MedPork intervention led to greater improvements in processing speed (P = 0.01) and mood (P = 0.03). Our findings demonstrate that a Mediterranean diet with added dairy foods is capable of delivering adequate calcium to ageing populations while providing cardiovascular and cognitive benefits. Further, a Mediterranean diet supplemented with fresh, lean pork offers comparable cardiovascular benefits to a low-fat diet and greater improvements to cognitive function and mood. Our findings are of particular relevance to non-Mediterranean populations at risk of cardiovascular disease and dementia, and offer two options for modifying the Mediterranean diet depending on dietary priorities.
The Blue Zones are known for healthy longevity and low rates of chronic disease. Common denominators between blue zones include social, environmental and spiritual foundations for good health, however there are key dietary contributors including mindful eating and a predominantly plant-based diet. the Mediterranean diet (MedDiet) is a plant-based diet and is reported to reduce the risk of overall mortality and cancer incidence, diabetes, neurodegenerative disease, heart attack and cardiovascular disease (CVD). Populations have enjoyed the health benefits of a MedDiet, for years, which could offer better health to Western countries which suffer from lifestyle diseases like obesity and heart disease. But how feasible is it to implement such a pattern beyond the Mediterranean sea? The MedLey study explored whether a MedDiet could be adhered to for 6 months and would improve CVD risk factors compared with habitual diet (HabDiet) in a population of older Australian adults. Volunteers were assessed at 3 points during the study (0, 3, 6 months) and12 months after the intervention had finished (18 months). 137 volunteers completed the trial and 128 volunteers completed the follow-up study. Participants completed a food frequency questionnaire and a 15-point MedDiet adherence score (MDAS; greater score = greater adherence) was calculated. Home BP was measured over 6 days, and cardiometabolic health outcomes were assessed. Data were analysed using intention-to-treat LMEM with a group x time interaction term comparing data at 0, 3, 6 and 18-months (12-months post-trial). At baseline the MedDiet score was 6.7 ± 0.2, 9.6 ± 0.2 at 4 months and 7.9 ± 0.3 at 18-months (p < .0001 to baseline and 4 months). The MedDiet resulted in improved systolic BP, endothelial dilatation, oxidative stress and plasma triglycerides in comparison with HabDiet, after 6 months (p < .05). These changes were not sustained at 18-months but did not completely return to baseline values. Principles of the MedDiet appeared to be somewhat maintained. Consumption of olive oil, legumes, fish and vegetables (p < .01) remained higher and discretionary food consumption (p = .02) remained lower at 18-months than baseline in the MedDiet group. We have shown that following a MedDiet for 6-months is feasible and results improvements in markers of CVD risk. Some principles of the MedDiet were maintained following trial completion, but ongoing support may be helpful in maintaining MedDiet adherence and improved health. To implement such a pattern on a population level, several considerations are required including provision of resources and information, ongoing support, creating supportive environments through a multi-settings approach.
The Mediterranean diet offers a range of health benefits. However, previous studies indicate that the restricted consumption of red meat in the diet may affect long-term sustainability in non-Mediterranean countries. A 24-week randomised controlled parallel cross-over design compared a Mediterranean diet supplemented with 2–3 serves per week of fresh, lean pork (MedPork) with a low-fat control diet (LF). Thirty-three participants at risk of CVD followed each intervention for 8 weeks, with an 8-week washout period separating interventions. The primary outcome was home-measured systolic blood pressure. Secondary outcomes included diastolic blood pressure, fasting lipids, glucose, insulin, C-reactive protein (CRP), body composition and dietary adherence. During the MedPork intervention, participants achieved high adherence to dietary guidelines. Compared with the MedPork intervention, the LF intervention led to greater reductions in weight (Δ = −0·65; 95 % CI −0·04, −1·25 kg, P = 0·04), BMI (Δ = −0·25; 95 % CI −0·03, −0·47 kg/m2, P = 0·01) and waist circumference (Δ = −1·40; 95 % CI −0·45, −2·34 cm, P < 0·01). No significant differences were observed for blood pressure, lipids, glucose, insulin or CRP. These findings indicate that Australians are capable of adhering to a Mediterranean diet with 2–3 weekly serves of fresh, lean pork. Larger intervention studies are now required to demonstrate clinical efficacy of the diet in populations with elevated blood pressure.
This literature review aimed to identify the range of methods used in after action reviews (AARs) of public health emergencies and to develop appraisal tools to compare methodological reporting and validity standards.
A review of biomedical and gray literature identified key approaches from AAR methodological research, real-world AARs, and AAR reporting templates. We developed a 50-item tool to systematically document AAR methodological reporting and a linked 11-item summary tool to document validity. Both tools were used sequentially to appraise the literature included in this study.
This review included 24 highly diverse papers, reflecting the lack of a standardized approach. We observed significant divergence between the standards described in AAR and qualitative research literature, and real-world AAR practice. The lack of reporting of basic methods to ensure validity increases doubt about the methodological basis of an individual AAR and the validity of its conclusions.
The main limitations in current AAR methodology and reporting standards may be addressed through our 11 validity-enhancing recommendations. A minimum reporting standard for AARs could help ensure that findings are valid and clear for others to learn from. A registry of AARs, based on a common reporting structure, may further facilitate shared learning. (Disaster Med Public Health Preparedness. 2019;13:618-625)
OBJECTIVES/SPECIFIC AIMS: The purpose of this study is to evaluate the extent of publication bias in anesthesia and to evaluate the characteristics of studies that are registered and unpublished. METHODS/STUDY POPULATION: We used the advanced search option and the key word “anesthesia” to identify anesthesia related studies in the ClinicalTrials.gov registry. For the purpose of this analysis we have randomly selected 50% of the anesthesia related studies from the year 2008–2013. We have collected information pertaining to drug/device study, origin, type, design, subspecialty, enrollment target, anesthesia type, and adult/ pediatric, sponsored/ investigator initiated, population studied and start and end date. Studies with an ongoing, terminated, or unknown status were excluded from the analysis. For results, we initially searched the results section associated with each study; also we searched for any publication link at the study result area of the registry. For studies with no results and publication links we searched on PubMed, Google Scholar, and Embase by trial registration number, study title, and investigators name for matching manuscripts. In addition, we also analyzed the proportion of studies with positive and negative conclusions. We used descriptive and univariate statistics to report the results. RESULTS/ANTICIPATED RESULTS: Overall, 5448 studies were identified within the queried timeframe. We have included 2649 studies in our final analysis and detailed analysis were performed for 1778 studies with the status “completed.” The mean, standard deviation of subjects enrolled in completed trials was 392.47±6378. Only 162 (9.9%) studies registered were in the pediatric population, and 1616 (90.9%) were in the adult population. Finally, of the reviewed studies, 1486 (83.6%) were investigator-initiated, 207 (11.6%) were sponsored, and 85 (4.8%) were registered as collaborated studies. Among the completed studies only 296 (16.6%) studies posted results to the result section of the registry. Additionally, a link associated with a publication was posted in only 393 (22.1%) of the studies. The proportion of studies with posted results were 208 (14%), 61 (29%) and 27 (31.8%) in investigator-initiated, sponsored, and collaborated studies p<0.001 respectively. In the 1778 studies we reviewed, 954 (53.7%) studies were associated with one publication. In the published studies, 721 (75.6%) studies reported a positive conclusion for their publication. DISCUSSION/SIGNIFICANCE OF IMPACT: Only, 53.7% of anesthesia related studies with a “complete” status in ClinicalTrials.gov were published. Furthermore, investigators fail to fulfill the requirement of making the results available in the results section of the registry. Lack of availability of published literature and the nonavailability of the results from these studies contributes to publication bias and also failure to honor the ethical responsibility of the investigator to share the results of the study with subjects and with the medical community around the world.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.