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Background: Infections lead to high mortality among patients on chronic dialysis; knowledge of multi-drug resistant infections is limited. The Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) conducts laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE) in 10 U.S. sites and carbapenem-resistant Acinetobacter baumannii (CRAB) in 9 U.S. sites. We investigated clinical characteristics, healthcare exposures, and outcomes of CRE and CRAB cases in persons on chronic dialysis from 2016-2021. Methods: Among EIP catchment-area residents on chronic dialysis, we defined a CRE case as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes (formerly Enterobacter aerogenes), Klebsiella oxytoca, Klebsiella pneumoniae, or Klebsiella variicola resistant to any carbapenem, from a normally sterile site or urine in a 30-day period. A CRAB case was defined as the first isolation of Acinetobacter baumannii complex resistant to any carbapenem (excluding ertapenem), from a normally sterile site or urine (or lower respiratory tract or wound since 2021) in a 30-day period. Medical records were reviewed. A case was considered colonized if the case culture had no associated infection type or colonization was documented in the medical record. Descriptive analyses, including analyses stratified by pathogen, were conducted. Results: Among 426 cases, 314 were CRE, and 112 were CRAB; most cases were male (235, 55.2%), Black (229, 53.8%), and 51-80 years old (320, 75.1%) (Table). An infection was associated with 363 (85.2%) case cultures; bloodstream infections (148; 40.8%), urinary tract infections (134; 36.9%), and pneumonia (17; 4.7%) were the most frequent. Overall, most cases had documented healthcare exposures (excluding outpatient dialysis) in the year before incident specimen collection, including: 366 (85.9%) hospitalizations, 235 (55.2%) surgeries, 209 (49.1%) long-term care facility stays, 54 (12.7%) long-term acute care facility stays. Additionally, 125 (29.3%) had an intensive care unit admission within the 7 days before incident specimen collection. Compared to CRE cases, a higher proportion of CRAB cases (a) had a long-term care facility stay (82/112 [73.2%] versus 127/314 [40.5%], P<.0001) or hospitalization (103/112 [92%] versus 263/314 [83.8%], P = .03) within the preceding year and (b) died within 30 days of incident specimen collection (40/112 [35.7%] versus 64/314 [20.4%], P = .001). Discussion: Among CRE and CRAB cases in persons on chronic dialysis, healthcare exposures were common, and mortality was high. Additional efforts to better describe the burden of these organisms and associated risk factors in the dialysis population are needed for tailoring infection prevention strategies to this vulnerable.
Background: The Centers for Disease Control and Prevention’s Emerging Infections Program conducts active laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE) and extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E). To better understand the U.S. epidemiology of these organisms among children, we determined the incidence of pediatric CRE and ESBL-E cases and described their clinical characteristics. Methods: Surveillance was conducted among children <18 years of age for CRE from 2016–2020 in 10 sites, and for ESBL-E from 2019–2020 in 6 sites. Among catchment-area residents, an incident CRE case was defined as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K. oxytoca, or K. pneumoniae in a 30-day period resistant to ≥1 carbapenem from a normally sterile site or urine. An incident ESBL-E case was defined as the first isolation of E. coli, K. pneumoniae, or K. oxytoca in a 30-day period resistant to any third-generation cephalosporin and non-resistant to all carbapenems from a normally sterile site or urine. Case records were reviewed. Results: Among 159 CRE cases, 131 (82.9%) were isolated from urine and 19 (12.0%) from blood; median age was 5 years (IQR 1–10) and 94 (59.1%) were female. Combined CRE incidence rate per 100,000 population by year ranged from 0.47 to 0.87. Among 207 ESBL-E cases, 160 (94.7%) were isolated from urine and 6 (3.6%) from blood; median age was 6 years (IQR 2–15) and 165 (79.7%) were female. Annual ESBL incidence rate per 100,000 population was 26.5 in 2019 and 19.63 in 2020. Incidence rates of CRE and ESBL-E were >2-fold higher in infants (children <1 year) than other age groups. Among those with data available, CRE cases were more likely than ESBL-E cases to have underlying conditions (99/158 [62.7%] versus 59/169 [34.9%], P<0.0001), prior healthcare exposures (74/158 [46.8%] versus 38/169 [22.5%], P<0.0001), and be hospitalized for any reason around time of their culture collection (75/158 [47.5%] versus 38/169 [22.5%], P<0.0001); median duration of admission was 18 days [IQR 3–103] for CRE versus 10 days [IQR 4–43] for ESBL-E. Urinary tract infection was the most frequent infection for CRE (89/158 [56.3%]) and ESBL-E (125/169 [74.0%]) cases. Conclusion: CRE infections occurred less frequently than ESBL-infections in U.S. children but were more often associated with healthcare risk factors and hospitalization. Infants had highest incidence of CRE and ESBL-E. Continued surveillance, infection prevention and control efforts, and antibiotic stewardship outside and within pediatric care are needed
A critical step in research on the epidemiology of post-traumatic stress disorder (PTSD) in low-resource settings is the validation of brief self-reported psychometric tools available in the public domain, such as the Impact Event Scale – Revised (IES-R).
Aims
We aimed to investigate the validity of the IES-R in a primary healthcare setting in Harare, Zimbabwe.
Method
We analysed data from a survey of 264 consecutively sampled adults (mean age 38 years; 78% female). We estimated the area under the receiver operating characteristic curve and sensitivity, specificity and likelihood ratios for different cut-off points of the IES-R, against a diagnosis of PTSD made using the Structured Clinical Interview for DSM-IV. We performed factor analysis to evaluate construct validity of the IES-R.
Results
The prevalence of PTSD was 23.9% (95% CI 18.9–29.5). The area under the curve for the IES-R was 0.90. At a cut-off of ≥47, the sensitivity of the IES-R to detect PTSD was 84.1 (95% CI 72.7–92.1) and specificity was 81.1 (95% CI 75.0–86.3). Positive and negative likelihood ratios were 4.45 and 0.20, respectively. Factor analysis revealed a two-factor solution, with both factors showing good internal consistency (Cronbach's factor-1 α = 0.95, factor-2 α = 0.76). In a post hoc analysis, we found the brief six-item IES-6 also performed well, with an area under the curve of 0.87 and optimal cut-off of 15.
Conclusions
The IES-R and IES-6 had good psychometric properties and performed well for indicating possible PTSD, but at higher cut-off points than those recommended in the Global North.
The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management, 7th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention,1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca.
Brain-derived neurotrophic factor (BDNF), which facilitates neuroplasticity and synaptogenesis, may be decreased in bipolar disorder, but has not been systematically investigated in people with newly diagnosed bipolar disorder and unaffected first-degree relatives.
Aims
To compare BDNF levels in patients with newly diagnosed bipolar disorder, their unaffected first-degree relatives and healthy controls.
Method
The study investigated plasma BDNF levels in patients (n = 371) with newly diagnosed bipolar disorder, their unaffected first-degree relatives (n = 98) and healthy controls (n = 200) using enzyme-linked immunosorbent assay. We further investigated associations between BDNF levels and illness-related variables and medication status.
Results
BDNF levels were found to be 22.0% (95% CI 1.107–1.343) higher in patients with bipolar disorder compared with healthy controls (P < 0.001) and 15.6% higher in unaffected first-degree relatives compared with healthy controls (95% CI 1.007–1.327, P = 0.04), when adjusting for age and gender. Further, BDNF levels were positively associated with duration of illness at a trend level (P = 0.05), age (P = 0.001) and use of anti-epileptic medication (P = 0.05).
Conclusions
These findings suggest that BDNF levels are not decreased in the early stages of bipolar disorder and in unaffected first-degree relatives contrasting with prior findings during later stages of the illness.
Previous literature has demonstrated a strong association between cigarette smoking, suicidal ideation and suicide attempts. This association has not previously been examined in a causal inference framework and could have important implications for suicide prevention strategies.
Aims
We aimed to examine the evidence for an association between smoking behaviours (initiation, smoking status, heaviness, lifetime smoking) and suicidal thoughts or attempts by triangulating across observational and Mendelian randomisation analyses.
Method
First, in the UK Biobank, we calculated observed associations between smoking behaviours and suicidal thoughts or attempts. Second, we used Mendelian randomisation to explore the relationship between smoking and suicide attempts and ideation, using genetic variants as instruments to reduce bias from residual confounding and reverse causation.
Results
Our observational analysis showed a relationship between smoking behaviour, suicidal ideation and attempts, particularly between smoking initiation and suicide attempts (odds ratio, 2.07; 95% CI 1.91–2.26; P < 0.001). The Mendelian randomisation analysis and single-nucleotide polymorphism analysis, however, did not support this (odds ratio for lifetime smoking on suicidal ideation, 0.050; 95% CI −0.027 to 0.127; odds ratio on suicide attempts, 0.053; 95% CI, −0.003 to 0.110). Despite past literature showing a positive dose-response relationship, our results showed no clear evidence for a causal effect of smoking on suicidal ideation or attempts.
Conclusions
This was the first Mendelian randomisation study to explore the effect of smoking on suicidal ideation and attempts. Our results suggest that, despite observed associations, there is no clear evidence for a causal effect.
Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homocysteine during pregnancy, particularly in a folic acid-fortified population.
Design:
Data were from the Ottawa and Kingston Birth Cohort of 8085 participants. We used multivariable regression analyses to identify factors associated with maternal homocysteine, adjusted for gestational age at bloodwork. Continuous factors were modelled using restricted cubic splines. A subgroup analysis examined the modifying effect of MTHFR 677C>T genotype on folate, in determining homocysteine concentration.
Setting:
Participants were recruited in Ottawa and Kingston, Canada, from 2002 to 2009.
Participants:
Women were recruited when presenting for prenatal care in the early second trimester.
Results:
In 7587 participants, factors significantly associated with higher homocysteine concentration were nulliparous, smoking and chronic hypertension, while factors significantly associated with lower homocysteine concentration were non-Caucasian race, history of a placenta-mediated complication and folic acid supplementation. Maternal age and BMI demonstrated U-shaped associations. Folic acid supplementation of >1 mg/d during pregnancy did not substantially increase folate concentration. In the subgroup analysis, MTHFR 677C>T modified the effect of folate status on homocysteine concentration.
Conclusions:
We identified determinants of maternal homocysteine relevant to the lowering of homocysteine in the post-folic acid fortification era, characterised by folate-replete populations. A focus on periconceptional folic acid supplementation and improving health status may form an effective approach to lower homocysteine.
The cost-effectiveness of molecular pathology testing is highly context dependent. The field is fast-moving, and national health technology assessment may not be relevant or timely for local decision makers. This study illustrates a method of context-specific economic evaluation that can be carried out in a limited timescale without extensive resources.
Methods
We established a multi-disciplinary group including an oncologist, pathologists and a health economist. We set out diagnostic and treatment pathways and costs using registry data, health technology assessments, guidelines, audit data, and estimates from the group. Sensitivity analysis varied input parameters across plausible ranges. The evaluation setting was the West of Scotland and UK NHS perspective was adopted. The evaluation was assessed against the AdHopHTA checklist for hospital-based health technology assessment.
Results
A context-specific economic evaluation could be carried out on a timely basis using limited resources. The evaluation met all relevant criteria in the AdHopHTA checklist. Health outcomes were expected to be at least equal to the current strategy. Annual cost savings of £637,000 were estimated resulting primarily from a reduction in the proportion of patients receiving intravenous infusional chemotherapy regimens. The result was not sensitive to any parameter. The data driving the main cost saving came from a small clinical audit. We recommended this finding was confirmed in a larger population.
Conclusions
The method could be used to evaluate testing changes elsewhere. The results of the case study may be transferable to other jurisdictions where the organization of cancer services is fragmented.
Edited by
Sarah Banks, Durham University,Angie Hart, University of Brighton,Kate Pahl, Manchester Metropolitan University,Paul Ward, Edge Hill University, Ormskirk
This chapter explores the interface between co-produced research and community development, drawing on work undertaken in North East England as part of the Imagine project. Discussion of the process and outcomes of Imagine North East provides fruitful material for contributing to perennial debates about whether certain forms of co-produced research (especially participatory action research) are, in fact, indistinguishable from community development. In this chapter we offer a brief overview of the work of Imagine North East before outlining the debates about the relationship between co-production and community development. We then examine three elements of Imagine North East: (1) an academic-led study of community development from the 1970s to the present; (2) a series of community development projects undertaken by local community-based organisations; and (3) a joint process of reflection and co-inquiry. We consider the role of co-produced research in challenging stigma, celebrating place and developing skills and community networks, and also the challenges of a co-inquiry approach.
Exploring community development from the outside and inside: The work of Imagine North East
Imagine North East was a partnership between 12 community-based organisations in Tyneside (including a local museum) and Durham University, officially running during 2014 and 2015, with dissemination and reflection work continuing in 2016. Community development featured in several ways. Not only did community-based sub-projects use processes of community development (mobilising people to work together) and generate community development outcomes (for example, strengthened communities, improved facilities) in their work for Imagine North East, but our study also had community development as its main focus. We adopted three approaches to the study of community development, as outlined below:
1. Studying community development from the outside: The starting point of the research was the community development projects of the 1970s in Benwell (Newcastle-upon-Tyne) and North Shields. These were part of Britain's first anti-poverty programme, combining community development work and research with a view to diagnosing and alleviating poverty locally (Loney, 1983; Banks and Carpenter, 2017). We also looked at community development processes over time (from the 1970s to the present) as these areas were subject to numerous regeneration schemes in which local people were more or less engaged. This research was largely done by academic researchers and then shared in the wider group.
Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.
Aims
We examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.
Method
Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and – using linear regression – total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).
Results
Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.
Conclusions
The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.
In 2012, Massachusetts enacted school competitive food and beverage standards similar to national Smart Snacks. These standards aim to improve the nutritional quality of competitive snacks. It was previously demonstrated that a majority of foods and beverages were compliant with the standards, but it was unknown whether food manufacturers reformulated products in response to the standards. The present study assessed whether products were reformulated after standards were implemented; the availability of reformulated products outside schools; and whether compliance with the standards improved the nutrient composition of competitive snacks.
Design
An observational cohort study documenting all competitive snacks sold before (2012) and after (2013 and 2014) the standards were implemented.
Setting
The sample included thirty-six school districts with both a middle and high school.
Results
After 2012, energy, saturated fat, Na and sugar decreased and fibre increased among all competitive foods. By 2013, 8 % of foods were reformulated, as were an additional 9 % by 2014. Nearly 15 % of reformulated foods were look-alike products that could not be purchased at supermarkets. Energy and Na in beverages decreased after 2012, in part facilitated by smaller package sizes.
Conclusions
Massachusetts’ law was effective in improving the nutritional content of snacks and product reformulation helped schools adhere to the law. This suggests fully implementing Smart Snacks standards may similarly improve the foods available in schools nationally. However, only some healthier reformulated foods were available outside schools.
Ira Aldridge -- a black New Yorker -- was one of nineteenth-century Europe's greatest actors. He performed abroad for forty-three years, winning more awards, honors, and official decorations than any of his professional peers. Billed as the "African Roscius," Aldridge developed a repertoire initially consisting of Shakespeare's Othello, melodramas about slavery, and farces that drew on his ability to sing and dance. By the time he began touring in Europe he was principally a Shakespearean actor, playing such classic characters as Shylock, Macbeth, Richard III, and King Lear. Although his frequent public appearances made him the most visible black man in the world by mid-nineteenth century, today Aldridge tends to be a forgotten figure, seldom mentioned in histories of British and European theater. This collection restores the luster to Aldridge's reputation by examining his extraordinary achievements against all odds. The early essays offer biographical information, while later essays examine his critical and popular reception throughout the world. Taken together, these diverse approaches to Aldridge offer a fuller understanding and heightened appreciation of a remarkable man who had an exceptionally interesting life and a spectacular career. Contributors: Cyril Bruyn Andrews, Nikola Batusic, Philip A. Bell, Keith Byerman, Ruth M. Cowhig, Nicholas M. Evans, Joost Groeneboer, Ann Marie Koller, Joyce Green MacDonald, Herbert Marshall, James J. Napier, Krzysztof Sawala, Gunner Sjögren, James McCune Smith, Hazel Waters, and Stanley B. Winters.
Bernth Lindfors is Professor Emeritus of English and African literatures at The University of Texas at Austin.
An updated compilation of published and new data of major-ion (Ca, Cl, K, Mg, Na, NO3, SO4) and methylsulfonate (MS) concentrations in snow from 520 Antarctic sites is provided by the national ITASE (International Trans-Antarctic Scientific Expedition) programmes of Australia, Brazil, China, Germany, Italy, Japan, Korea, New Zealand, Norway, the United Kingdom, the United States and the national Antarctic programme of Finland. The comparison shows that snow chemistry concentrations vary by up to four orders of magnitude across Antarctica and exhibit distinct geographical patterns. The Antarctic-wide comparison of glaciochemical records provides a unique opportunity to improve our understanding of the fundamental factors that ultimately control the chemistry of snow or ice samples. This paper aims to initiate data compilation and administration in order to provide a framework for facilitation of Antarctic-wide snow chemistry discussions across all ITASE nations and other contributing groups. The data are made available through the ITASE web page (http://www2.umaine.edu/itase/content/syngroups/snowchem.html) and will be updated with new data as they are provided. In addition, recommendations for future research efforts are summarized.
Charles Jennens's Il Moderato (1740) is the longest English text written ab initio for Handel to set, yet there has been little critical examination of it. That is unsurprising. Modern taste does not warm to its theme or its diction. This chapter seeks to orientate the words of Il Moderato in the taste of Handel's time. It forms one of an intermittent series of attempts to fathom Handel's L'Allegro, il Penseroso ed il Moderato (1740–41), that apparently limpid, yet endlessly referential, composition. It will suggest why, when Handel wrote to Jennens from Dublin, ‘I assure you that the Words of the Moderato are vastly admired’, which is possibly the politest sentence that Handel ever wrote, he may have been quite truthful, rather than polite in the sense of insincerely tactful.
Diction
A contemporary reviewer of L'Allegro, il Penseroso ed il Moderato, whose essay includes high praise for Milton's twin poems L'Allegro and Il Penseroso, thought that the words of Il Moderato could well stand comparison with them:
Never was there in any Language so beautiful a Collection of Images suited to each of those Tempers, as in the two original Poems … had they been printed entire, and annex'd to the Drama, in a small Character [font], it would have been an agreeable Compliment paid to the Audience, had heighten'd the Relish of the Musick, and been no Injustice done to the Fitter of them for the Theatre; whose dramatic Moderato (or Mean between them) can very well bear being compared together.
The reviewer wishes that the wordbook had included Milton's original poems, so as to ‘heighten the relish’ of listeners by enabling them to compare Milton with what had been made of him by librettist and composer. The wish contains an assumption that some at least of Handel's audience really did pay attention to his librettists’ words in relation to his settings of them, and suggests that Handel was wise to respond to demands for music united with good English texts. It is in this context of attentive comparison that the reviewer finds that Jennens's words ‘can very well bear being compared’ with Milton's.
To examine the association between BMI and folate concentrations in serum and red blood cells (RBC) in pregnant women.
Design
A cross-sectional comparison of folate concentrations in serum and RBC sampled simultaneously from the same individual.
Setting
The Ottawa Hospital and Kingston General Hospital, Ontario, Canada.
Subjects
Pregnant women recruited between 12 and 20 weeks of gestation.
Results
A total of 869 pregnant women recruited from April 2008 to April 2009 were included in the final analysis. Serum folate was inversely associated and RBC folate positively associated with BMI, after adjusting for folic acid supplementation, age, gestational age at blood sample collection, race, maternal education, annual income, smoking and MTHFR 677C→T genotype. In stratified analyses, this differential association was significant in women with the MTHFR CC variant. In women with the CT and TT variants, the differential associations were in the same direction but not significant. Folic acid supplementation during pregnancy did not alter the differential association of BMI with serum and RBC folate concentration. This indicates that the current RBC folate cut-off approach for assessing risk of neural tube defects in obese women may be limited.
Conclusions
BMI is inversely associated with serum folate and positively associated with RBC folate in pregnant women, especially for those with the MTHFR CC variant.