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We conducted a pilot study of implementing community health workers (CHWs) to assist patients with hypertension and social needs. As part of clinical care, patients identified as having an unmet need were referred to a CHW. We evaluated changes in blood pressure and needs among 35 patients and conducted interviews to understand participants’ experiences. Participants had a mean age of 54.1 years and 29 were Black. Twenty-six completed follow-up. Blood pressure and social needs improved from baseline to 6 months. Participants reported being accepting of CHWs, but also challenges with establishing a relationship with a CHW and being unclear about their role.
OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.
Complications from pulmonary hypertension are one of the leading contributors to morbidity and mortality post-cardiopulmonary bypass surgery in children with CHD. Pulmonary vasodilator therapies are commonly used post-operatively, but the optimal target patient population, therapy choice, timing of therapy initiation, and duration of therapy are not well defined.
Methods:
We used PubMed and EMBASE to identify studies from 2000 to 2020 investigating the use of pulmonary vasodilator therapy post-cardiopulmonary bypass in children aged 0–18 years. To ensure eligibility criteria, studies were systematically reviewed by two independent reviewers.
Results:
We identified 26 studies of 42,971 children across four medication classes; 23 were single centre, 14 were prospective, and 11 involved randomisation (four of which employed a placebo-control arm). A disproportionate number of children were from a single retrospective study of 41,872 patients. Definitions varied, but change in pulmonary haemodynamics was the most common primary outcome, used in 14 studies. Six studies had clinical endpoints, with mortality the primary endpoint for two studies. Treatment with inhaled nitric oxide, iloprost, and sildenafil all resulted in improved haemodynamics in specific cohorts of children with post-operative pulmonary hypertension, although improved outcomes were not consistently demonstrated across all treated children. Iloprost may be a cheaper alternative to inhaled nitric oxide with similar haemodynamic response.
Conclusion:
Studies were predominantly single-centre, a control arm was rarely used in randomised studies, and haemodynamic endpoints varied significantly. Further research is needed to reduce post-operative morbidity and mortality from pulmonary hypertension in children with CHD.
To determine the optimal antithrombotic agent choice, timing of initiation, dosing and duration of therapy for paediatric patients undergoing cardiac surgery with cardiopulmonary bypass.
Methods:
We used PubMed and EMBASE to systematically review the existing literature of clinical trials involving antithrombotics following cardiac surgery from 2000 to 2020 in children 0–18 years. Studies were assessed by two reviewers to ensure they met eligibility criteria.
Results:
We identified 10 studies in 1929 children across three medications classes: vitamin K antagonists, cyclooxygenase inhibitors and indirect thrombin inhibitors. Four studies were retrospective, five were prospective observational cohorts (one of which used historical controls) and one was a prospective, randomised, placebo-controlled, double-blind trial. All included were single-centre studies. Eight studies used surrogate biomarkers and two used clinical endpoints as the primary endpoint. There was substantive variability in response to antithrombotics in the immediate post-operative period. Studies of warfarin and aspirin showed that laboratory monitoring levels were frequently out of therapeutic range (variably defined), and findings were mixed on the association of these derangements with bleeding or thrombotic events. Heparin was found to be safe at low doses, but breakthrough thromboembolic events were common.
Conclusion:
There are few paediatric prospective randomised clinical trials evaluating antithrombotic therapeutics post-cardiac surgery; most studies have been observational and seldom employed clinical endpoints. Standardised, validated endpoints and pragmatic trial designs may allow investigators to determine the optimal drug, timing of initiation, dosing and duration to improve outcomes by limiting post-operative morbidity and mortality related to bleeding or thrombotic events.
Background: Discussions around driving cessation between clinicians and dementia patients are challenging. Patients view giving up their license as losing their independence. We sought to develop a tool that enables standardized and consistent driving messaging across clinicians working in a specialist memory clinic, across the span of cognitive disorders Methods: We developed a driving recommendations generator that allows clinicians to produce information handouts personalized to individual patient capabilities and needs. Clinicians select from a list of established recommendations that were developed with neurologist and geriatrician input, and consistent with provincial requirements. Recommendations cover patients’ current driving ability, road safety examinations, alternate transportation, and license revocation. Early driving retirement is emphasized and encouraged, to proactively support patients’ choices, safety and independence. Recommendation and handouts are printed for the patients. Results: Patients reported that the recommendations were easy to read and understand, and helped them to implement physician suggestions. All surveyed clients recommended continuing to provide such recommendations to future patients and families. Clinicians agreed that the tool helped them to save time, and simplified the process of finding accurate information to provide patients. Conclusions: Clinicians have found the system timesaving and useful for simplifying the process of providing helpful, informative resources for patients.
Paediatric cardiac surgery on cardiopulmonary bypass induces substantial physiologic changes that contribute to post-operative morbidity and mortality. Fluid overload and oedema are prevalent complications, routinely treated with diuretics. The optimal diuretic choice, timing of initiation, dose, and interval remain largely unknown.
Methods:
To guide clinical practice and future studies, we used PubMed and EMBASE to systematically review the existing literature of clinical trials involving diuretics following cardiac surgery from 2000 to 2020 in children aged 0–18 years. Studies were assessed by two reviewers to ensure that they met eligibility criteria.
Results:
We identified nine studies of 430 children across four medication classes. Five studies were retrospective, and four were prospective, two of which included randomisation. All were single centre. There were five primary endpoints – urine output, acute kidney injury, fluid balance, change in serum bicarbonate level, and required dose of diuretic. Included studies showed early post-operative diuretic resistance, suggesting higher initial doses. Two studies of ethacrynic acid showed increased urine output and lower diuretic requirement compared to furosemide. Children receiving peritoneal dialysis were less likely to develop fluid overload than those receiving furosemide. Chlorothiazide, acetazolamide, and tolvaptan demonstrated potential benefit as adjuncts to traditional diuretic regimens.
Conclusions:
Early diuretic resistance is seen in children following cardiopulmonary bypass. Ethacrynic acid appears superior to furosemide. Adjunct diuretic therapies may provide additional benefit. Study populations were heterogeneous and endpoints varied. Standardised, validated endpoints and pragmatic trial designs may allow investigators to determine the optimal diuretic, timing of initiation, dose, and interval to improve post-operative outcomes.
Targeted drug development efforts in patients with CHD are needed to standardise care, improve outcomes, and limit adverse events in the post-operative period. To identify major gaps in knowledge that can be addressed by drug development efforts and provide a rationale for current clinical practice, this review evaluates the evidence behind the most common medication classes used in the post-operative care of children with CHD undergoing cardiac surgery with cardiopulmonary bypass.
Methods:
We systematically searched PubMed and EMBASE from 2000 to 2019 using a controlled vocabulary and keywords related to diuretics, vasoactives, sedatives, analgesics, pulmonary vasodilators, coagulation system medications, antiarrhythmics, steroids, and other endocrine drugs. We included studies of drugs given post-operatively to children with CHD undergoing repair or palliation with cardiopulmonary bypass.
Results:
We identified a total of 127 studies with 51,573 total children across medication classes. Most studies were retrospective cohorts at single centres. There is significant age- and disease-related variability in drug disposition, efficacy, and safety.
Conclusion:
In this study, we discovered major gaps in knowledge for each medication class and identified areas for future research. Advances in data collection through electronic health records, novel trial methods, and collaboration can aid drug development efforts in standardising care, improving outcomes, and limiting adverse events in the post-operative period.
Infants with moderate-to-severe CHD frequently undergo cardiopulmonary bypass surgery in childhood. Morbidity and mortality are highest in those who develop post-operative low cardiac output syndrome. Vasoactive and inotropic medications are mainstays of treatment for these children, despite limited evidence supporting their use.
Methods:
To help inform clinical practice, as well as the conduct of future trials, we performed a systematic review of existing literature on inotropes and vasoactives in children after cardiac surgery using the PubMed and EMBASE databases. We included studies from 2000 to 2020, and the patient population was defined as birth – 18 years of age. Two reviewers independently reviewed studies to determine final eligibility.
Results:
The final analysis included 37 papers. Collectively, selected studies reported on 12 different vasoactive and inotropic medications in 2856 children. Overall evidence supporting the use of these drugs in children after cardiopulmonary bypass was limited. The majority of studies were small with 30/37 (81%) enrolling less than 100 patients, 29/37 (78%) were not randomised, and safety and efficacy endpoints differed widely, limiting the ability to combine data for meta-analyses.
Conclusion:
Vasoactive and inotropic support remain critical parts of post-operative care for children after cardiopulmonary bypass surgery. There is a paucity of data for the selection and dosing of vasoactives and inotropes for these patients. Despite the knowledge gaps that remain, numerous recent innovations create opportunities to rethink the conduct of clinical trials in this high-risk population.
In a world dizzyingly shifted on its axis since 9/11, nothing has aided understanding of the profound twenty-first-century geopolitical slippages more than the revelations from Julian Assange's WikiLeaks site and the actions of whistle-blower Edward Snowden. Much has been written about the pair but little has investigated their persona and pronouncements onscreen. This article sets out to compare and contrast Snowden's and Assange's real as well as fictional cinematic portrayals, therefore. We find that their screen image conforms to notions of star celebrity but at the same time also challenges surveillance activism itself, on film as well as within wider political frames of reference. The movies about them may have deliberately foregrounded reactions towards the politics of surveillance, but that agenda has been conditioned by responses not only towards Assange and Snowden but also to the filmmakers producing these texts. We give resonance, in other words, to a wider discourse that goes beyond the cinematic in contemporary surveillance culture. There is an interlocutory discourse at play that sees cinema as not just a disruptive presence, but now more than ever as an active participant in mapping out the terrain under investigation. The challenge this presence brings to activism, we conclude, affects film's capacity to expose and contest contemporary state surveillance.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Methods
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
Results
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Conclusions
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
In this paper we review the interaction of El Niño Southern Oscillation (ENSO) variability and warming trends recorded in ice-core records from high-altitude tropical glaciers, discuss the implications of the warming trends for the glaciers and consider the societal implications of glacier retreat. ENSO has strong impacts on meteorological phenomena that directly or indirectly affect most regions on the planet and their populations. Many tropical ice fields have provided continuous annually resolved proxy records of climatic and environmental variability preserved in measurable parameters, especially oxygen and hydrogen isotopic ratios (δ18O, δD) and the net mass balance (accumulation). These records present an opportunity to examine the nature of tropical climate variability in greater detail and to extract new information on linkages between rising temperatures on tropical glaciers and equatorial Pacific sea surface temperatures in critical ENSO indicator regions. The long-term climate records from a collection of high-altitude tropical ice cores provide the longer-term context essential for assessing the significance of the magnitude and rate of current climate changes that are in large measure driving glacier retreat. The well-documented ice loss on Quelccaya in the Peruvian Andes, Naimona’nyi in the Himalaya, Kilimanjaro in eastern Africa and the ice fields near Puncak Jaya in Papua, Indonesia, presents a grim future for low-latitude glaciers. The ongoing melting of these ice fields (response) is consistent with model predictions for a vertical amplification of temperature in the tropics (driver) and has serious implications for the people who live in these areas.
Some speleothems (CaCO3 cave deposits) can be demonstrated to have been formed in oxygen isotopic equilibrium with their parent seepage waters and thus a record of relative fluctuations in depositional temperature can be obtained from the δ18O variations in successive growth layers of such deposits. These temperature fluctuations reflect variations in the average annual air temperature at the surface above the cave, and therefore permit inference of past continental climate changes. Equilibrium deposits have been obtained from caves in San Luis Potosi, Bermuda, Kentucky, West Virginia, Iowa, and Alberta, ranging in age from 200,000 years BP to the present, as determined by 230Th/234U dating of the speleothems. The δ18O time curves for the six sites show the following synchronous climatic fluctuations: warm periods from 190 to 165 and from 120 to 100 Ka, at 60 and 10 Ka, and cold periods from 95 to 65 and from 55 to 20 Ka. The periods of thermal maxima correspond in time to the interglacial periods of the marine foraminiferal isotopic and faunal temperature records and to periods of high sea stand as observed from radiometric dating of raised coral reefs. Maxima and minima in insolation appear to be synchronous with this record as well.
Reservations on technical and theoretical grounds in the use of the consumer surplus approach to measure benefits of government programs have often appeared in the literature. Therefore, this paper uses an alternative approach in a case study to estimate the annual economic surplus created in South Carolina from deregulating tobacco production. Impacts of deregulation on cropping patterns and income on representative tobacco farms, and distribution of benefits in the economy are examined. Results of this study indicate that deregulation stimulates the economy and would increase the net value added by $5.8 million in the long run.
During the 1890s Elliott Coues (1842–1899), one of America's greatest ornithologists, edited several exploration narratives about the American Northwest, including Lewis and Clark's Travels. Coues tracked down the manuscript journals of two of Lewis and Clark's contemporaries, fur trader Alexander Henry (1765–1814) and geographer David Thompson (1770–1857), employees of the Northwest Company. Coues' abridged and edited version of Henry's text, accompanied by notes that draw heavily on Thompson's scientific records, appeared in 1897 in three volumes. Despite the deep prejudice evident in Henry's writing, Coues judged it a reliable account of his unscrupulous business dealings, and of the harsh realities he observed among many different First Nations peoples. Volume 2 covers 1808–14, when Henry travelled in Saskatchewan and Alberta, crossed the Great Divide, and traded along the Columbia River. This volume also contains Coues' original Volume 3, a comprehensive index of people and places.
During the 1890s Elliott Coues (1842–1899), one of America's greatest ornithologists, edited several exploration narratives about the American Northwest, including Lewis and Clark's Travels. Coues tracked down the manuscript journals of two of Lewis and Clark's contemporaries, fur trader Alexander Henry (1765–1814) and geographer David Thompson (1770–1857), employees of the Northwest Company. Coues' abridged and edited version of Henry's text, accompanied by notes that draw heavily on Thompson's scientific records, appeared in 1897 in three volumes; in this reissue the index volume is included in Volume 2. Despite the deep prejudice evident in Henry's writing, Coues judged it a reliable account of his unscrupulous business dealings, and of the harsh realities he observed among many different First Nations peoples. Volume 1 covers the period from 1799 to 1808, when Henry travelled along the Red River and set up the Pembina River trading post.
Although cognitive deficits are common in patients with chronic heart failure (CHF), no study to date has investigated whether these deficits extend to the capacity to execute delayed intentions (prospective memory, PM). This is a surprising omission given the critical role PM plays in correctly implementing many important CHF self-care behaviors. The present study aimed to provide the first empirical assessment of PM function in people with CHF. The key dependent measure was a laboratory measure of PM that closely simulates PM tasks in daily life – Virtual Week. A group comparison design was used, with 30 CHF patients compared to 30 demographically matched controls. Background measures assessing executive functions, working memory, and verbal memory were also administered. The CHF group exhibited significant PM impairment, with difficulties generalizing across different types of PM tasks (event, time, regular, irregular). The CHF group also had moderate deficits on several of the background cognitive measures. Given the level of impairment remained consistent even on tasks that imposed minimal demands on memory for task content, CHF-related difficulties most likely reflects problems with the prospective component. However, exploratory analyses suggest that difficulties with retrospective memory and global cognition (but not executive control), also contribute to the PM difficulties seen in this group. The implications of these data are discussed, and in particular, it is argued that problems with PM may help explain why patient engagement in CHF self-care behaviors is often poor. (JINS, 2015, 21, 1–10)
Dry bean (Phaseolus vulgaris L.) consumption is associated with reduced risk for a number of chronic diseases. In westernised societies, dry bean consumption is particularly low (approximately 2–4 kg/capita per year) and little information is available about the safety of increasing dietary intake in humans to achieve levels that prevent and control chronic diseases. In anticipation of a human intervention study to address the safety and efficacy of increasing bean consumption, a dose–response study with dietary beans was conducted to establish whether increased bean consumption in rats exhibits changes indicative of hepatic stress or toxicity. Transcript levels from a panel of stress and toxicity-related genes were analysed in female Sprague–Dawley rats fed a dose range of dietary beans that bracketed amounts relevant to human consumption globally. Cooked red bean was incorporated into a purified diet formulation at 0, 7·5, 15, 30 or 60 % w/w for the assessment of adaptive patterns of gene expression using quantitative PCR array. Of the eighty-four genes evaluated, the expressions of Cyp3a11, Cyp7a1, Fmo1, Gstm1, Mif and Ugt1a6 were elevated, whereas the expression of Hspa8 was down-regulated. Liver gene expression was not modulated in a manner indicative of an adverse response. Only the expression of the cholesterol 7α hydoxylase and UDP-glucuronosyltransferase genes increased in a dose-dependent manner at nutritionally relevant dietary bean concentrations. These candidate genes may contribute to the health benefits attributed to increased bean consumption.