bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicentre, pragmatic, cluster randomised, controlled feasibility trial of the POD system of care
Authors: Young John , Green John , Farrin Amanda , Collinson Michelle , Hartley Suzanne , Smith Jane , Teale Elizabeth , Siddiqi Najma , Inouye Sharon K
Published: February 2020

Objective

to provide a preliminary estimate of the effectiveness of the prevention of delirium (POD) system of care in reducing incident delirium in acute hospital wards and gather data for a future definitive randomised controlled trial.

Design

cluster randomised and controlled feasibility trial.

Setting

sixteen acute care of older people and orthopaedic trauma wards in eight hospitals in England and Wales.

Participants

patients 65 years and over admitted to participating wards during the trial period.

Interventions

participating wards were randomly assigned to either the POD programme or usual care, determined by existing local policies and practices. The POD programme is a manualised multicomponent delirium prevention intervention that targets 10 risk factors for delirium. The intervention wards underwent a 6-month implementation period before trial recruitment commenced. Main outcome measure incidence of new-onset delirium measured using the Confusion Assessment Method (CAM) measured daily for up to 10 days post consent.

Results

out of 4449, 3274 patients admitted to the wards were eligible. In total, 714 patients consented (713 registered) to the trial, thirty-three participants (4.6%) withdrew. Adherence to the intervention was classified as at least medium for seven wards. Rates of new-onset delirium were lower than expected and did not differ between groups (24 (7.0%) of participants in the intervention group versus 33 (8.9%) in the control group; odds ratio (95% confidence interval) 0.68 (0.37–1.26); P = 0.2225).

Conclusions

based on these findings, a definitive trial is achievable and would need to recruit 5220 patients in 26 two-ward hospital clusters.

Trial registration: ISRCTN01187372. Registered 13 March 2014.
Continuing the Intervention: Past, Present, and Future Pathways for Native Studies and Early American History
Authors: DeLucia Christine M.
Published: February 2020

David Silverman offers a critical appraisal of two prizewinning works in Native American and Indigenous studies (NAIS), Our Beloved Kin: A New History of King Philip’s War, by Lisa Brooks, and Memory Lands: King Philip’s War and the Place of Violence in the Northeast, by Christine M. DeLucia. Silverman’s review treats the methodology associated with NAIS with some skepticism, offering the opportunity for a lively discussion about the merits and perils of community-engaged history scholarship. Four scholars of Native American history, including DeLucia, respond, defending new approaches to Indigenous history represented by these recent works.
Legal Principles, Constitutional Principles, and Judicial Review
Authors: Zhou Han-Ru
Published: February 2020

Principles form part and parcel of our law and legal discourse, so much so that we seldom think of what they are and what they entail. For centuries they have been invoked daily to interpret and argue about the law. But when it comes to matters of constitutional law, principles are further called upon to perform a perennially controversial function: to help police the boundaries of state action. In most common law jurisdictions with a written constitution, this function of principles runs against the generally accepted view that the exercise of judicial review must ultimately be governed and restricted by the terms of the national constitution. This Article argues that the exercise of judicial review based on principles is not confined to that view, once the relationship between principles and the constitution is unpacked and recontextualized.

While the English-language literature on principles over the past half-century has been dominated by a select group of Anglo-American scholars, there is a wealth of untapped insights from other parts of the world. One of the major contributions by continental legal theorists even predates the earliest modern Anglo-American writings on the subject by more than a decade. Overall, the law literature in common law and civil law systems reveals a significant degree of commonalities in the basic characters of principles despite the absence of initial evidence of transsystemic borrowings. The wider conceptual inquiry also displays a shift in the focus of the debate, from the protracted search for a clear-cut distinction between rules and principles towards a redefinition of principles’ relationship with “written” law, be it in the form of a civil code or a constitutional instrument. From this inquiry reemerge “unwritten” principles not deriving from codified or legislated law although they have been used to develop the law. Translated into the constitutional domain, these unwritten principles bear no logical connection with the terms of the constitution. Their main functions cover the entire spectrum from serving as interpretive aids to making law by filling gaps. The theoretical framework fits with an ongoing four-century-old narrative of the evolution of constitutional principles and judicial review across most common law-based systems. Constitutional principles are another area where Anglo-American law and legal discourse is less exceptional and more universal than what many assume. Throughout modern Western history, legal battles have been fought and ensuing developments have been made on the grounds of principles. Our law and jurisprudence remain based on them.
The Burden of Placental Histopathology in Stillbirths Associated With Maternal Obesity
Authors: Avagliano Laura , Monari Francesca , Po’ Gaia , Salerno Cristina , Mascherpa Margaret , Maiorana Antonino , Facchinetti Fabio , Bulfamante Gaetano Pietro
Published: February 2020

Objectives

Obesity is an increasing health problem that has become a common medical disorder among women of childbearing age, representing worldwide a risk factor for stillbirth. The aim of the study is to evaluate the association between placental histopathologic findings and obesity in stillbirth.

Methods

Placentas were analyzed according to the Amsterdam consensus statement. Histologic findings in stillbirth from obese and lean mothers were analyzed and compared with those observed in liveborn controls.

Results

Stillbirth in obese mothers displayed placental pathology in all gestational ages, mostly at term of pregnancy. The most observed placental lesions were those consistent with maternal vascular malperfusion of the placental bed. Decidual arteriopathy and placental infarcts appeared specifically associated with maternal obesity. Moreover, obese women with stillbirth showed the highest cumulative number of placental lesions.

Conclusions

Considering the significant association between stillbirth, maternal obesity, and placental histopathologic findings, health care providers should be aware about the importance of placental examination in obese women, especially in stillborn cases. The high prevalence of lesions consistent with vascular malperfusion of the placental bed suggests that stillbirth prevention strategies in obese women should rely on the development of tools to study and improve decidual artery functioning early in pregnancy.
cDNA-Based Mutation Screening Using a Combination of High-Resolution Melting Curve and Fragment Analysis Facilitates Efficient CCR4 Mutation Analysis in Adult T-Cell Leukemia/Lymphoma
Authors: Mizuta Shumpei , Yamane Noriko , Mononobe Saya , Komai Takao , Koba Yusuke , Kawata Takahito , Ukyo Naoya , Tamekane Akira , Watanabe Mitsumasa
Published: February 2020

Objectives

C-C chemokine receptor type 4 (CCR4) proteins are expressed on the neoplastic cells of adult T-cell leukemia/lymphoma (ATLL). As the mutation status of CCR4 gene is reported to correlate with significant clinical information such as prognosis and response to mogamulizumab, we aimed to establish a screening method that is suitable for clinical laboratory tests.

Methods

In 34 patients with ATLL, CCR4 mutation analysis, high-resolution melting (HRM) analysis, fragment analysis, and direct sequencing were performed using both genomic DNA and complementary DNA (cDNA). Furthermore, 38 cases of asymptomatic carriers of human T-cell leukemia virus type 1 (HTLV-1) were screened for CCR4 mutation.

Results

Mutation analysis by direct sequencing of 34 ATLL clinical samples detected CCR4 mutation in four genomic DNA samples and seven cDNA samples, and two novel mutations were identified. All CCR4 mutations detected by direct sequencing were positive for HRM analysis and/or fragment analysis. CCR4 mutation was not detected in the asymptomatic carriers of HTLV-1.

Conclusions

CCR4 mutation screening by a combination of HRM and fragment analysis using cDNA is a simple and practical method, and it will contribute to better decision making for a therapeutic strategy, providing a rapid CCR4 mutational status to clinicians.
Snowfall, Temperature, and the Risk of Death From Myocardial Infarction: A Case-Crossover Study
Authors: Gan Wen Qi , Henderson Sarah B , Mckee Geoffrey , Yuchi Weiran , McLean Kathleen E , Hong Kris Y , Auger Nathalie , Kosatsky Tom
Published: February 2020

Previous research has associated snowfall with risk of myocardial infarction (MI). Most studies have been conducted in regions with harsh winters; it remains unclear whether snowfall is associated with risk of MI in regions with milder or more varied climates. A case-crossover design was used to investigate the association between snowfall and death from MI in British Columbia, Canada. Deaths from MI among British Columbia residents between October 15 and March 31 from 2009 to 2017 were identified. The day of each death from MI was treated as the case day, and each case day was matched to control days drawn from the same day of the week during the same month. Daily snowfall amount was assigned to case and control days at the residential address, using weather stations within 15 km of the residence and 100 m in elevation. In total, 3,300 MI case days were matched to 10,441 control days. Compared with days that had no snowfall, odds of death from MI increased 34% (95% confidence interval: 0%, 80%) on days with heavy snowfall (≥5 cm). In stratified analysis of deaths from MI as a function of both maximum temperature and snowfall, risk was significantly increased on snowfall days when the temperature was warmer.
ProCaff: protein–carbohydrate complex binding affinity database
Authors: Siva Shanmugam N R , Jino Blessy J , Veluraja K , Michael Gromiha M
Published: February 2020

Motivation

Protein–carbohydrate interactions perform several cellular and biological functions and their structure and function are mainly dictated by their binding affinity. Although plenty of experimental data on binding affinity are available, there is no reliable and comprehensive database in the literature.

Results

We have developed a database on binding affinity of protein–carbohydrate complexes, ProCaff, which contains 3122 entries on dissociation constant (Kd), Gibbs free energy change (ΔG), experimental conditions, sequence, structure and literature information. Additional features include the options to search, display, visualization, download and upload the data.

Availability and implementation

The database is freely available at http://web.iitm.ac.in/bioinfo2/procaff/. The website is implemented using HTML and PHP and supports recent versions of major browsers such as Chrome, Firefox, IE10 and Opera.

Contact

gromiha@iitm.ac.in

Supplementary information

Supplementary data are available at Bioinformatics online.
Within-day temporal isolation of two species of Iris (Iridaceae) sharing the same pollinator
Authors: Liu Rong , Gao Yike , Fan Zhuping , Wang Xinzi , Xiao Jianhua , Zhang Qixiang
Published: February 2020

Knowledge of factors driving reproductive isolation is essential to understand the process of speciation. To study the reproductive isolation of two closely related species with overlapping flowering seasons, Iris domestica and Iris dichotoma, we compared their reproductive system, floral biology and pollination biology. The results indicated that I. domestica was facultatively xenogamous, whereas I. dichotoma was facultatively autogamous. Although the two species differed significantly in floral colour, floral diameter, floral structure, nectar volume, flower opening and closing times, they shared the same diurnal pollinator, the honeybee Apis cerana. The frequency of pollination by A. cerana did not differ significantly between the two species, but honeybee pollination of I. domestica was more efficient compared with that of I. dichotoma. Despite the difference in floral structure between the two species, both species deposited pollen on the same parts of the body of honeybees. The temporal partitioning of within-day flowering times between I. domestica (from 07.15 to 08.15 h to 18.00 to 19.00 h) and I. dichotoma (from 15.45 to 16.15 h to 22.00 to 23.00 h), together with the time memory of honeybees, meant that the two species did not overlap in the time of their pollination, thus leading to temporal isolation as a major driver of reproductive isolation between the two species.
Knockout of mouse receptor accessory protein 6 leads to sperm function and morphology defects†
Authors: Devlin Darius J , Agrawal Zaneveld Smriti , Nozawa Kaori , Han Xiao , Moye Abigail R , Liang Qingnan , Harnish Jacob Michael , Matzuk Martin M , Chen Rui
Published: February 2020

Receptor accessory protein 6 (REEP6) is a member of the REEP/Ypt-interacting protein family that we recently identified as essential for normal endoplasmic reticulum homeostasis and protein trafficking in the retina of mice and humans. Interestingly, in addition to the loss of REEP6 in our knockout (KO) mouse model recapitulating the retinal degeneration of humans with REEP6 mutations causing retinitis pigmentosa (RP), we also found that male mice are sterile. Herein, we characterize the infertility caused by loss of Reep6. Expression of both Reep6 mRNA transcripts is present in the testis; however, isoform 1 becomes overexpressed during spermiogenesis. In vitro fertilization assays reveal that Reep6 KO spermatozoa are able to bind the zona pellucida but are only able to fertilize oocytes lacking the zona pellucida. Although spermatogenesis appears normal in KO mice, cauda epididymal spermatozoa have severe motility defects and variable morphological abnormalities, including bent or absent tails. Immunofluorescent staining reveals that REEP6 expression first appears in stage IV tubules within step 15 spermatids, and REEP6 localizes to the connecting piece, midpiece, and annulus of mature spermatozoa. These data reveal an important role for REEP6 in sperm motility and morphology and is the first reported function for a REEP protein in reproductive processes. Additionally, this work identifies a new gene potentially responsible for human infertility and has implications for patients with RP harboring mutations in REEP6.
Accessing surgical care for esophageal cancer: patient travel patterns to reach higher volume center
Authors: Diaz Adrian , Burns Sarah , D’Souza Desmond , Kneuertz Peter , Merritt Robert , Perry Kyle , Pawlik Timothy M
Published: February 2020

While better outcomes at high-volume surgical centers have driven the regionalization of complex surgical care, access to high-volume centers often requires travel over longer distances. We sought to evaluate the travel patterns among patients undergoing esophagectomy to assess willingness of patients to travel for surgical care. The California Office of Statewide Health Planning database was used to identify patients who underwent esophagectomy between 2005 and 2016. Total distance traveled, as well as whether a patient bypassed the nearest hospital that performed esophagectomy to get to a higher volume center, was assessed. Overall 3,269 individuals underwent an esophagectomy for cancer in 154 hospitals; only five hospitals were high volume according to Leapfrog standards. Median travel time to a hospital that performed esophagectomy was 26 minutes (IQR: 13.1–50.7). The overwhelming majority of patients (85%) bypassed the nearest providing hospital to seek care at a destination hospital. Among patients who bypassed a closer hospital, only 36% went to a high-volume hospital. Of the 2,248 patients who underwent esophagectomy at a low-volume center, 1,491 patients had bypassed a high-volume hospital. Of the remaining 757 patients who did not bypass a high-volume hospital, half of the individuals would have needed to travel less than an additional hour to reach a high-volume center. Nearly two-thirds of patients undergoing an esophagectomy for cancer received care at a low-volume center; 85% of patients either bypassed a high-volume hospital or would have needed to travel less than an additional hour to reach a high-volume center.
Associations between the supply and utilization of primary care and newborn, children and maternal health in rural counties of Guangdong Province, China
Authors: Ke Naiqi , Ma Yuanzhu , Luo Zhuojun , Xu Shuyi , Kuang Li
Published: February 2020

Background

The Chinese government is ambitious regarding strengthening the primary care system for women and children. Primary care contributes to better health outcomes among neonates, infants, children and pregnant women, especially for vulnerable groups. However, few published studies have examined this issue in China.

Objective

This study examined whether greater supply and utilization of primary care was associated with improved health outcomes among targeted populations in the total and interprovincial migrant populations in the rural counties of Guangdong Province, China.

Methods

This ecological study analysed annual panel data from all 63 rural counties in Guangdong Province from 2014 to 2016 (n = 189). A linear random-effects panel data model was applied.

Results

Higher proportions of primary care visits were significantly associated with reduced incidences of low birth weight (P < 0.05) and preterm birth rates (P < 0.05) for the total population, and were significantly associated with reduced infant (P < 0.1) and under-five (P < 0.01) mortality rates for migrants. Greater primary care physician supply was significantly associated with reduced maternal mortality (P < 0.1) rates among migrants. However, primary care indicators were insignificant for both the total and migrant populations regarding neonatal mortality rates, as well as the infant and under-five mortality rates in the total population (P > 0.1).

Conclusions

These findings support existing evidence regarding associations between primary care and improved health outcomes among newborns, children and pregnant women, especially for disadvantaged populations. However, associations were not significant for all studied health outcomes, implying the need for further study.
A Study of Faster-Z Evolution in the Great Tit (Parus major)
Authors: Hayes Kai , Barton Henry J , Zeng Kai
Published: February 2020

Sex chromosomes contribute substantially to key evolutionary processes such as speciation and adaptation. Several theories suggest that evolution could occur more rapidly on sex chromosomes, but currently our understanding of whether and how this occurs is limited. Here, we present an analysis of the great tit (Parus major) genome, aiming to detect signals of faster-Z evolution. We find mixed evidence of faster divergence on the Z chromosome than autosomes, with significantly higher divergence being found in ancestral repeats, but not at 4- or 0-fold degenerate sites. Interestingly, some 4-fold sites appear to be selectively constrained, which may mislead analyses that use these sites as the neutral reference (e.g., dN/dS). Consistent with other studies in birds, the mutation rate is significantly higher in males than females, and the long-term Z-to-autosome effective population size ratio is only 0.5, significantly lower than the expected value of 0.75. These are indicative of male-driven evolution and high variance in male reproductive success, respectively. We find no evidence for an increased efficacy of positive selection on the Z chromosome. In contrast, the Z chromosome in great tits appears to be affected by increased genetic drift, which has led to detectable signals of weakened intensity of purifying selection. These results provide further evidence that the Z chromosome often has a low effective population size, and that this has important consequences for its evolution. They also highlight the importance of considering multiple factors that can affect the rate of evolution and effective population sizes of sex chromosomes.
Under the Roof of Rebels: Civilian Targeting After Territorial Takeover in Sierra Leone
Authors: Oswald Christian , Sauter Melanie , Weber Sigrid , Williams Rob
Published: February 2020

Do rebels target civilians as part of the process of establishing control in their territories? This research note shows that transition periods after rebels gain territorial control are remarkably violent for civilians. Speaking to the civilian victimization and rebel governance literature, we investigate the immediate time period after rebels successfully capture and hold territory. We argue that rebels use violence to gain compliance in newly captured territories until they are able to build up local capacities and institutions for peaceful governance. To test this argument, we draw on methodological advances in integrating event data and combine multiple datasets to study patterns of violence perpetrated by the Revolutionary United Front in Sierra Leone from 1997 to 2001. The findings of our spatiotemporal analysis show that civilian targeting increases in the period after rebels capture territory from the government compared to areas without territorial takeover, suggesting that life under the roof of rebels is initially more dangerous for civilians.
Real-life management of drug–drug interactions between antiretrovirals and statins
Authors: Courlet Perrine , Livio Françoise , Alves Saldanha Susana , Scherrer Alexandra , Battegay Manuel , Cavassini Matthias , Stoeckle Marcel , Decosterd Laurent Arthur , Marzolini Catia ,   the Swiss HIV Cohort Study, Aebi-Popp K , Anagnostopoulos A , Battegay M , Bernasconi E , Böni J , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Kahlert C R , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Ledergerber B , Martinetti G , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nicca D , Paioni P , Pantaleo G , Perreau M , Rauch A , Rudin C , Scherrer A U , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Vernazza P , Wandeler G , Weber R , Yerly S
Published: February 2020

Background

PIs cause drug–drug interactions (DDIs) with most statins due to inhibition of drug-metabolizing enzymes and/or the hepatic uptake transporter OATP1B1, which may alter the pharmacodynamic (PD) effect of statins.

Objectives

To assess the management of DDIs between antiretrovirals (ARVs) and statins in people living with HIV (PLWH) considering statin plasma concentrations, compliance with dosing recommendations and achievement of lipid targets.

Methods

PLWH of the Swiss HIV Cohort Study were eligible if they received a statin concomitantly with ARVs. HDL, total cholesterol (TC) and statin plasma concentration were measured during follow-up visits. Individual non-HDL and TC target values were set using the Framingham score and the 2018 European AIDS Clinical Society recommendations.

Results

Data were analysed for rosuvastatin (n = 99), atorvastatin (n = 92), pravastatin (n = 46) and pitavastatin (n = 21). Rosuvastatin and atorvastatin underdosing frequently led to suboptimal PD response. Insufficient lipid control was observed with PIs despite high atorvastatin concentrations, likely explained by inhibition of OATP1B1 resulting in less statin uptake in the liver. Target lipid values were more often achieved with unboosted integrase inhibitors due to both their favourable DDI profiles and neutral effect on lipids. Insufficient lipid control was common with pravastatin and pitavastatin regardless of co-administered ARVs and despite using maximal recommended statin doses. The latter suggests lower efficacy compared with rosuvastatin or atorvastatin.

Conclusions

Suboptimal management of DDIs with statin underdosing was observed in 29% of prescriptions. Integrase inhibitor-based regimens and/or treatment with rosuvastatin or atorvastatin should be favoured in patients with refractory dyslipidaemia.
Editorial Assessment and Processing
Authors: Fontanarosa Phil , Christiansen Stacy , Flanagin Annette
Published: February 2020

The Editorial Assessment and Processing chapter of the 11th edition of the AMA Manual of Style describes the procedures that some scientific journals use to evaluate and then process articles for publication. For the evaluation process of peer review, not only the selection of reviewers but also criteria for manuscript assessment, masked (“blind”) or unmasked review, revisions, and appeals are described. The steps an accepted manuscript then undergoes as it moves toward publication (manuscript editing, composition and page makeup, and proofreading), as well as issue makeup (including advertising placement and final review) are outlined. Finally, postpublication review and corrections are emphasized as important parts of the process.
Plurals
Authors: Gregoline Brenda
Published: February 2020

The Plurals chapter of the 11th edition of the AMA Manual of Style describes how plurals are formed, parenthetical plurals, when not to use plurals, and plurals of symbols, letters, numbers, and years. Also considered are collective nouns, Latin and Greek vs English plurals, plurals of microorganisms and abbreviations, and false singulars.
Non-English Words, Phrases, and Accent Marks
Authors: Gregoline Brenda
Published: February 2020

The Non-English Words, Phrases, and Accent Marks chapter of the 11th edition of the AMA Manual of Style includes guidelines on the use of italics, translation of titles, capitalization and punctuation, and accent marks (diacritics). A table showing examples of accent marks and usage concludes the chapter.
Eponyms
Authors: Gregoline Brenda
Published: February 2020

The Eponyms chapter of the 11th edition of the AMA Manual of Style addresses the use of eponymous vs noneponymous terms and, on the sometimes debated issue of the possessive vs nonpossessive form for eponyms, continues to recommend the nonpossessive form.
Greek Letters
Authors: Gregoline Brenda
Published: February 2020

The Greek Letters chapter of the 11th edition of the AMA Manual of Style not only includes a table of capital and lowercase Greek letters, but addresses when to use the Greek letter rather than the word and when capital letters are appropriate after a Greek letter. New to the chapter is a discussion of Greek letters in an electronic format.
Units of Measure
Authors: Fischer Lauren , Frank Paul
Published: February 2020

The Units of Measure chapter of the 11th edition of the AMA Manual of Style begins with guidance on the International System of Units (SI) and includes an updated SI conversion table (laboratory reference ranges are no longer included because of differences among laboratories worldwide). Conventions related to format, style, and punctuation of units (eg, exponents, plurals, subject-verb agreement, spelling out units of measure, abbreviations, punctuation, hyphens, and spacing) and capitalization and expression of products and quotients of unit symbols are addressed. A detailed description of use of numerals with units is included, as are specific discussions of units of length, area, volume, and mass; temperature; time; visual acuity; pressure; pH; solutions and concentrations; energy; drug doses; laboratory values; and radiation. The list of international currencies and symbols has been updated and expanded. A change in policy to include a space after the number and before degrees Celsius and degrees Fahrenheit follows SI standards.
Study Design and Statistics
Authors: Livingston Edward H.
Published: February 2020

The Study Design and Statistics chapter of the 11th edition of the AMA Manual of Style begins with a description of the parts of a scientific manuscript and the role of each part: Abstract, Introduction, Methods, Results, and Discussion. The features unique to different study types are outlined: randomized clinical trials, parallel-design double-blind trials, crossover trials, equivalence and noninferiority trials, cluster trials, observational studies, cohort studies, case-control studies, case series, comparative effectiveness research, meta-analyses, cost-effectiveness/cost-benefit analyses, quality improvement studies, and survey studies. Because correct treatment depends on accurate diagnosis, attention is given to various types of diagnostic tests. A large glossary of statistical terms indicates the appropriate applications of commonly used statistical techniques, providing definitions, presentation, and tips and guidelines for correct usage. Many new terms have been added to this glossary since the previous edition.
Racial differences in patient consent policy preferences for electronic health information exchange
Authors: Turvey Carolyn L , Klein Dawn M , Nazi Kim M , Haidary Susan T , Bouhaddou Omar , Hsing Nelson , Donahue Margaret
Published: February 2020

Objective

This study aimed to explore the association between demographic variables, such as race and gender, and patient consent policy preferences for health information exchange as well as self-report by VHA enrollees of information continuity between Veterans Health Administration (VHA) and community non-VHA heath care providers.

Materials and Methods

Data were collected between March 25, 2016 and August 22, 2016 in an online survey of 19 567 veterans. Three questions from the 2016 Commonwealth Fund International Health Policy Survey, which addressed care continuity, were included. The survey also included questions about consent policy preference regarding opt-out, opt-in, and “break the glass” consent policies.

Results

VHA enrollees had comparable proportions of unnecessary laboratory testing and conflicting information from providers when compared with the United States sample in the Commonwealth Survey. However, they endorsed medical record information being unavailable between organizations more highly. Demographic variables were associated with gaps in care continuity as well as consent policy preferences, with 56.8% of Whites preferring an opt-out policy as compared with 40.3% of Blacks, 44.9% of Hispanic Latinos, 48.3% of Asian/Pacific Islanders, and 38.3% of Native Americans (P < .001).

Discussion

Observed large differences by race and ethnicity in privacy preferences for electronic health information exchange should inform implementation of these programs to ensure cultural sensitivity. Veterans experienced care continuity comparable to a general United States sample, except for less effective exchange of health records between heath care organizations. VHA followed an opt-in consent policy at the time of this survey which may underlie this gap.
A2 THE BOWEL CLEANSING NATIONAL INITIATIVE (BCLEAN): PREDICTORS OF INADEQUATE BOWEL PREPARATION
Authors: Barkun A N , Martel M , Epstein I L , Hallé P , Hilsden R J , James P , Rostom A , Sey M , Singh H , Sultanian R , Telford J J , Von Renteln D
Published: February 2020

Background

Adequate bowel cleansing before colonoscopy is, in theory, a simple concept but the high rate of inadequate or incomplete bowel cleanliness and its consequences have been the subject of many studies, guidelines, and meta- analyses. The complexity resides in all the pre-endoscopic factors surrounding preparation intake that may? influence quality of the bowel preparation.

Aims

To identify preendoscopic variables associated with inadequate bowel preparation

Methods

In this randomized trial conducted in adult outpatients in 10 Canadian hospitals, all early morning (AM) colonoscopies were scheduled between 7h30AM and 10h30AM and patients were randomized to PEG low volume or high- volume split-dose or high- volume day before. Later colonoscopies (PM) were scheduled between 10h30AM and 16h30PM and patients were randomized to PEG low-volume or high- volume split-dose or low- volume same day. A secondary random allocation assigned patients to a clear fluid or low residue diet. Inadequate bowel preparation was identified on the Boston Bowel Preparation Scale with a total score <6 with any of the 3 colonic segments subscores <2). All preendoscopic variables such as patients related factors, diet and type of bowel preparation were evaluated between groups with chi-square, Fisher’s exact or t-test where appropriate. All variables found to be significantly associated with a clean preparation on univariable analysis at the P=0.15 level were used to construct a multivariable model. Because of stratified randomization by time with possible resulting differing confounders, AM and PM patients were analysed separately.

Results

Over 29 months, 1726 patients were stratified in the AM group and 1750 patients in the PM group. 16.9% had inadequate bowel preparation in the AM group and 9.8% in the PM group. Pre-endoscopic variables associated with an inadequate bowel cleanliness in AM colonoscopy were a non screening indication (OR 1.36, 95%CI 1.04–1.78), a Charlson score>0 (OR 1.36, 95% 1.03–1.80) and a low residue diet (OR 1.53, 95%CI 1.17–2.01). Amongst PM colonoscopies, variables associated with an inadequate bowel cleanliness were increased age (OR 1.03, 95% 1.01–1.04), a non screening indication (OR 1.90 95%CI 1.35–2.70); a Charlson score>0 (OR 1.63, 95%CI 1.15–2.32), and a low residue diet (OR 1.41, 95%CI 1.01; 1.98).

Conclusions

In this large randomized trial, amongst patients undergoing an AM colonoscopy, pre- endoscopic factors associated with an inadequate bowel preparation were a non screening indication, comorbidities and a low residue diet. Amongst PM colonoscopy patients, in addition to these variables, an increased age was also associated with an inadequate bowel preparation.

Funding Agencies

received arm-length funding from Pendopharm Inc.
A3 TREATMENT IN DISPROPORTIONATELY MINORITY HOSPITALS IS ASSOCIATED WITH AN INCREASED MORTALITY IN END STAGE LIVER DISEASE
Authors: Alotaibi A S , Brahmania M , Mooney O , Rush B
Published: February 2020

Background

Racial and ethnic disparities continue to remain a barrier in delivery of health care across the United States. Care for minority patients tends to be clustered into a small number of providers at minority hospitals, which has been associated with worse clinical outcomes in several conditions. However, the outcomes of treatment in end stage liver disease (ESLD) patients at predominately minority hospitals is unknown.

Aims

To evaluate in-hospital mortality rate among ESLD patients treated in minority hospitals compared to non-minority hospitals.

Methods

We utilized the Nationwide Inpatient Sample (NIS) to conduct a retrospective nationwide cohort analysis. All patients >18 years of age admitted with ESLD were included in the analysis. A multivariate logistic regression model was used to study the mortality rate among ESLD patients treated at minority hospitals compared to ESLD patients treated at non-minority hospitals.

Results

A total of 53,281,467 hospitalizations from the 2008–2014 NIS sample were analyzed. There were 163,470 patients with ESLD that met inclusion criteria. There were 10,178 (6.2%) and 31,226 (19.1%) ESLD patients treated at Black and Hispanic minority hospitals, respectively. In hospital mortality rate for all races were 8.0% and 8.1% in Black and Hispanic minority hospitals, respectively, compared to 7.3% in non-minority hospitals (p<0.01). On multivariate analysis, treatment of ESLD in Black and Hispanic minority hospitals were associated with a 11% (OR: 1.11; 95% CI: 1.03–1.20; p<0.01) and 22% (OR: 1.22; 95% CI: 1.09–1.37; p<0.01) increased odds of death, respectively, compared to treatment in a non-minority hospital regardless of patient race.

Conclusions

ESLD patient treated at minority hospital are faced with an increased mortality rate regardless of a patients race. The current study highlights a quality gap that needs improvement to effect overall survival among ESLD patients.

Funding Agencies

None
A7 DEVELOPING NEW TOOLS TO IDENTIFY NOVELS TARGETS TO OVERCOME TREATMENT RESISTANCE IN ESOPHAGEAL CANCER
Authors: Douchin J , Lemaire N , Kérignard E , Giroux V
Published: February 2020

Background

In Canada, patients with esophageal cancer have the 2nd worst 5-year survival rate (14%). Esophageal squamous cell carcinoma (ESCC) is the most common esophageal cancer type worldwide. Its high mortality rate is partly due to the treatment resistance acquired by patients, which has mostly been attributed to the presence of cancer stem cells (CSCs). Therefore, targeting CSCs is a promising strategy to improve treatment and survival of ESCC patients. CSCs are a subpopulation of tumor cells presenting high self-renewal and multipotent capacities, and therefore largely contribute to tumor heterogeneity in addition to treatment resistance.

Aims

In this study, we aim to establish human ESCC cell lines resistant to radiotherapy (TE15RR), chemotherapy (TE15CR) and both (TE15RCR), and study the relationship between resistance acquisition and CSC properties;

Methods

To do so, we exposed human ESCC cell line TE15 to chronic doses of radiotherapy (2 Gy/week for a total dose of 60 Gy) and/or increasing doses of chemotherapy (5-FU (1, 2, 5, 10 and 15mM)). We harvested samples at different time points to fully investigate resistance acquisition process. Then, we further validated resistance and properties of the resistant TE15 cell lines.

Results

We confirmed that TE15RR cells are less susceptible to radiation than control cells and showed that they are more proliferative at baseline using MTT assays. Moreover, we demonstrated that TE15RR cells comprise a higher proportion of CD24high/CD44high CSC population using flow cytometry. We also found that they express higher levels of ALDH1, another well-known CSC marker, by qPCR and Western Blot. Our preliminary observations also suggest a higher invasive phenotype in TE15RR cells in limited dilution spheroid assay than in control cells supporting that TE15RR cells display CSC-like properties. TE15CR and TE15RCR cell lines were validated using similar approaches. Finally, mass spectrometry was performed to compare the proteomic profile of the resistant cell lines to the control cell line in order to identify key players in treatment resistance acquisition.

Conclusions

Brief, we developed radioresistant, chemoresistant and radiochemoresistant human ESCC cell lines and demonstrated that resistance acquisition correlates with CSC enrichment. Mass spectrophotometry revealed significant proteomic differences between resistant and control cell lines, which should lead to the identification of novel targets to overcome resistance in ESCC patients.

Funding Agencies

Canada research chair TIER 2
A12 SKIN EXPOSURE TO NARROW BAND UVB LIGHT MODULATES THE HUMAN INTESTINAL MICROBIOME
Authors: Bosman E S , Albert A Y , Dutz J P , Vallance B
Published: February 2020

Background

The recent worldwide rise in idiopathic immune and inflammatory diseases such as multiple sclerosis and inflammatory bowel diseases has been linked to Western society-based changes in lifestyle and environment. These include decreased exposure to sunlight/UVB light and subsequent impairment in the production of vitamin D, as well as dysbiotic changes in the makeup of the gut microbiome. Despite their association, it is unclear if there are any direct links between UVB light and the gut microbiome.

Aims

In this study we investigated whether exposing the skin to Narrow Band Ultraviolet B (NB-UVB) light to increase serum vitamin D levels would also modulate the makeup of the human intestinal microbiota.

Methods

The effects of NB-UVB light were studied in a clinical pilot study using a healthy human female cohort (n=21). Participants were divided into those that took vitamin D supplements throughout the winter prior to the start of the study (VDS+) and those who did not (VDS-).

Results

After three full-body NB-UVB light exposures within the same week, the serum 25(OH)D levels of participants increased on average 7.3 nmol/L. The serum response was negatively correlated to the starting 25-hydroxy vitamin D (25(OH)D) serum concentration. Fecal microbiota composition analysis using 16S rRNA sequencing showed that exposure to NB-UVB significantly increased alpha and beta diversity in the VDS- group whereas there were no changes in the VDS+ group. Bacteria from several families were enriched in the VDS- group after the UVB exposures according to a Linear Discriminant Analysis (LDA) prediction, including Lachnospiracheae, Rikenellaceae, Desulfobacteraceae, Clostridiales vadinBB60 group, Clostridia Family XIII, Coriobacteriaceae, Marinifilaceae, and Ruminococcus. The serum 25(OH)D concentrations showed a positive correlation with the relative abundance of the Lachnospiraceae, specifically members of the Lachnopsira and Fusicatenibacter genera.

Conclusions

This is the first study to show that humans with low 25(OH)D serum levels display overt changes in their intestinal microbiome in response to NB-UVB skin exposure and increases in 25(OH)D levels, suggesting the existence of a novel skin-gut axis that could be used to promote intestinal homeostasis and health.

Funding Agencies

NRCBC Childrens Hospital Research Institute
A42 MICROBIAL METABOLISM OF DIETARY TRYPTOPHAN ENHANCES ARYL HYDROCARBON RECEPTOR ACTIVATION: IMPLICATIONS FOR IBD
Authors: Rondeau L , Clarizio A V , Jury J , Gibson D L , Bercik P , Sokol H , Caminero Fernandez A
Published: February 2020

Background

Intestinal immune homeostasis is maintained by the interplay between microbiota and the mucosal immune system. Changes in gut microbiota have been associated with chronic intestinal conditions, such as inflammatory bowel disease (IBD). The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by dietary and environmental stimuli to control immune responses in the gut and homeostatic mechanisms at mucosal surfaces. In IBD, AhR expression is downregulated. Major agonists of AhR in the gut include microbial tryptophan metabolites such as indole derivatives, which are decreased in IBD patients. The mechanisms involved in tryptophan metabolism by bacteria and their implications in AhR activation and thus IBD pathogenesis are not well understood.

Aims

To investigate whether tryptophan metabolism by intestinal bacteria participates in AhR activation and IBD pathogenesis.

Methods

Microbiota profiles (16S rRNA Illumina) and activation of AhR (luciferase reporter assay) were determined in fecal samples from IBD patients (n=10) and healthy volunteers (n=10). Germ-free C57BL/6 mice were colonized with fecal slurries of 2 healthy subjects and 4 IBD patients (n=4 mice/donor) by oral gavage (humanized-mice). All mice were fed irradiated tryptophan diets with 0.1% or 1% tryptophan content for 14 days. Simultaneously, SPF Mucin 2 (Muc2) deficient mice (C57BL/6 background), which develop colitis spontaneously, were fed tryptophan diets (0.1%, 0.3% and 1% content). Activation of AhR was measured in feces using an AhR luciferase reporter assay. Inflammation was determined by immunohistochemistry and the characterization of immune infiltrate in colon cross-sections. Bacteria from human and mouse fecal samples were isolated and screened for their ability to produce indoles using biochemical reagents. Positive bacteria were identified by colony PCR and 16S rRNA Sanger sequencing.

Results

IBD patients had an altered fecal microbiota with a lower capacity to activate AhR compared to healthy subjects. Colonization of mice with microbiota from healthy subjects induced greater activation of AhR compared to mice colonized with microbiota from patients with IBD. Furthermore, increasing dietary tryptophan composition rescued the capacity to activate AhR. In Muc2 deficient mice, dietary tryptophan treatment enhanced AhR activation capacity and reduced infiltration of innate immune cells before the onset of colitis. Several AhR agonist producing bacterial species were identified and will be used in future experiments.

Conclusions

Activation of AhR is dependent on the gut microbiota and disease status of the donor. Dietary intervention with tryptophan enhances AhR activation capacity and may be a potential therapeutic avenue in IBD individuals with intestinal dysbiosis.

Funding Agencies

Farncombe Family Digestive Health Research Institute, Biocodex Microbiota Foundation
A59 DECREASING HOSPITALIZATIONS AND SURGERIES IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED COHORT STUDY
Authors: Dheri A , Kuenzig E , Mack D , Murthy S , Kaplan G G , Benchimol E I
Published: February 2020

Background

Health services use in inflammatory bowel disease (IBD) patients cost the Canadian healthcare system $1.3 billion per year, but recent changes to care in children with IBD may have altered trends in health services use. Characterization of these trends would aid health policy makers plan for the healthcare needs of IBD children.

Aims

To quantify time trends in IBD health services use in children and all-cause health services use in children with and without IBD using a population-based cohort.

Methods

Using the Ontario Crohn’s and Colitis Cohort, children <18y with IBD diagnosed between 1994–2012 in Ontario were identified using validated algorithms from health administrative data, and matched on age, sex, rurality, and income to children without IBD. We evaluated trends in the number of IBD-specific and all-cause outpatient visits, emergency department (ED) visits, and hospitalizations using negative binomial regression. Cox proportional hazards regression models were used to describe changes in the hazard of intestinal resection (Crohn’s disease; CD) and colectomy (ulcerative colitis; UC) over time. Results are reported as annual percentage change (with 95%CI) for events within 5 years from the diagnosis/index date.

Results

IBD-specific hospitalization rates decreased by 2.5% (95%CI 1.8–3.2%) per year, but all-cause hospitalization rates in children without IBD decreased faster (APC, 95%CI: 4.3%, 3.5–5.1%, difference in rates p-value=0.0028). The hazard of intestinal resection for CD decreased by 6.0% (95%CI 4.6–7.3%) per year and the hazard of colectomy for UC decreased by 3.0% (95%CI 0.7–5.2%) per year. IBD-specific outpatient visit rates increased after 2005 by 4.0% (95%CI 3.1–4.9%) per year. Similar trends were not observed in children without IBD.

Conclusions

Decreasing hazards of intestinal resection and colectomy in children with IBD suggest changes in disease management, including more care being provided on an outpatient basis. Decreased hospitalization rates in IBD were mirrored by similar decreases in non-IBD children, indicating universal care changes. Understanding why these trends are occurring may help us better understand how to provide optimal care to children with IBD.

Funding Agencies

CIHRCanGIEC