bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laxative co-medication and changes in defecation patterns during opioid use
Authors: Bruin Frans de , Hek Karin , Lieshout Jan van , Verduijn Monique , Langendijk Pim , Bouvy Marcel , Teichert Martina 
Published: September 2018

Introduction Opioid-induced constipation is a clinically relevant side effect and a cause of potentially avoidable drug-related hospital admissions. Objectives To describe the presence of laxative co-medication, the reasons for not starting laxatives and to evaluate changes in stool patterns of opioid initiators. Methods In this observational study community pharmacists evaluated the availability of laxative co-medication in starting opioid users and registered reasons for non-use. Two opioid initiators per pharmacy were invited to complete questionnaires (‘Bristol stool form scale’ and ‘Rome III Diagnostic Questionnaire for the Adult Functional Gastrointestinal Disorders’) on their defecation prior to and during opioid use. Descriptive statistics and Chi square tests were used to analyse reasons for non-use of laxatives and changes in defecation patterns. Results Eighty-one pharmacists collected data from 460 opioid initiators. Of those, 344 (74.8%) used laxatives concomitantly. Main reason not to use laxatives was that either prescribers or patients did not consider them necessary. Sixty-seven (89.3%) of the 75 opioid starters with two questionnaires completed were not constipated at opioid start. Eleven of them (16%) developed constipation during opioid use (Chi square p=0.003). At follow-up within laxative users 10.6% were constipated compared to 20.7% in subjects without laxatives. Conclusion One in four opioid starters did not dispose of laxative co-medication, mainly because they were not considered necessary by either the prescriber or the patient. The prevalence of constipation doubled during opioid use. A watchful waiting strategy for the use of laxative co-medication might include a monitoring of defecation patterns with validated questionnaires.
Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma
Authors: Tun Han W. , Johnston Patrick B. , DeAngelis Lisa M. , Atherton Pamela J. , Pederson Levi D. , Koenig Patricia A. , Reeder Craig B. , Omuro Antonio M. Padula , Schiff David , O’Neill Brian , Pulido Jose , Jaeckle Kurt A. , Grommes Christian , Witzig Thomas E. 
Published: September 2018

AbstractThe combination of pomalidomide (POM) and dexamethasone (DEX) was evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL) to determine the maximal tolerated dose (MTD) of POM as the primary objective, and overall response rate (ORR), progression-free survival (PFS), and safety profile as secondary objectives. A cohorts-of-3 study design was used with a dose-escalation schedule consisting of POM (3, 5, 7, or 10 mg) orally daily for 21 days every 28 days and DEX 40 mg orally every week. After 2 cycles, POM was continued alone until disease progression, intolerance, or subject withdrawal. Following MTD determination, the MTD cohort was expanded. Twenty-five of 29 patients with the median of 3 prior treatments were eligible for assessment as per international PCNSL collaborative group criteria. The MTD of POM was 5 mg daily for 21 days every 28 days. Whole-study ORR was 48% (12 of 25; 95% confidence interval [CI], 27.8%, 68.7%) with 6 complete response (CR), 2 complete response, unconfirmed (CRu), and 4 partial response (PR). MTD cohort ORR was 50% (8 of 16; 95% CI, 24.7%, 75.4%) with 5 CR, 1 CRu, and 2 PR. Median PFS was 5.3 months (whole study) and 9 months (for responders). One patient had pseudoprogression. Grade 3/4 hematologic toxicities included neutropenia (21%), anemia (8%), and thrombocytopenia (8%). Grade 3/4 nonhematologic toxicities included lung infection (12%), sepsis (4%), fatigue (8%), syncope (4%), dyspnea (4%), hypoxia (4%), respiratory failure (8%), and rash (4%). POM/DEX treatment is feasible with significant therapeutic activity against relapsed/refractory PCNSL and PVRL. This trial was registered at www.clinicaltrials.gov as #NCT01722305.
Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements
Authors: Luchtel Rebecca A. , Dasari Surendra , Oishi Naoki , Pedersen Martin Bjerregård , Hu Guangzhen , Rech Karen L. , Ketterling Rhett P. , Sidhu Jagmohan , Wang Xueju , Katoh Ryohei , Dogan Ahmet , Kip N. Sertac , Cunningham Julie M. , Sun Zhifu , Baheti Saurabh , Porcher Julie C. , Said Jonathan W. , Jiang Liuyan , Hamilton-Dutoit Stephen Jacques , Møller Michael Boe , Nørgaard Peter , Bennani N. Nora , Chng Wee-Joo , Huang Gaofeng , Link Brian K. , Facchetti Fabio , Cerhan James R. , d’Amore Francesco , Ansell Stephen M. , Feldman Andrew L. 
Published: September 2018

Key PointsDUSP22-rearranged ALCLs belong to a distinct subset of ALCLs lacking activated STAT3. DUSP22-rearranged ALCLs have a unique molecular signature characterized by DNA hypomethylation and an immunogenic phenotype.
EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation
Authors: McLaughlin Lauren P. , Rouce Rayne , Gottschalk Stephen , Torrano Vicky , Carrum George , Wu Meng-Fen , Hoq Fahmida , Grilley Bambi , Marcogliese Andrea M. , Hanley Patrick J. , Gee Adrian P. , Brenner Malcolm K. , Rooney Cliona M. , Heslop Helen E. , Bollard Catherine M. 
Published: September 2018

Abstract
There is a Blood Commentary on this article in this issue.
Chromosome Y–encoded antigens associate with acute graft-versus-host disease in sex-mismatched stem cell transplant
Authors: Wang Wei , Huang Hu , Halagan Michael , Vierra-Green Cynthia , Heuer Michael , Brelsford Jason E. , Haagenson Michael , Scheuermann Richard H. , Telenti Amalio , Biggs William , Pearson Nathaniel M. , Udell Julia , Spellman Stephen , Maiers Martin , Kennedy Caleb J. 
Published: September 2018

Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a curative option for blood cancers, but the coupled effects of graft-versus-tumor and graft-versus-host disease (GVHD) limit its broader application. Outcomes improve with matching at HLAs, but other factors are required to explain residual risk of GVHD. In an effort to identify genetic associations outside the major histocompatibility complex, we conducted a genome-wide clinical outcomes study on 205 acute myeloid leukemia patients and their fully HLA-A–, HLA-B–, HLA-C–, HLA-DRB1–, and HLA-DQB1–matched (10/10) unrelated donors. HLA-DPB1 T-cell epitope permissibility mismatches were observed in less than half (45%) of acute GVHD cases, motivating a broader search for genetic factors affecting clinical outcomes. A novel bioinformatics workflow adapted from neoantigen discovery found no associations between acute GVHD and known, HLA-restricted minor histocompatibility antigens (MiHAs). These results were confirmed with microarray data from an additional 988 samples. On the other hand, Y-chromosome–encoded single-nucleotide polymorphisms in 4 genes (PCDH11Y, USP9Y, UTY, and NLGN4Y) did associate with acute GVHD in male patients with female donors. Males in this category with acute GVHD had more Y-encoded variant peptides per patient with higher predicted HLA-binding affinity than males without GVHD who matched X-paralogous alleles in their female donors. Methods and results described here have an immediate impact for allo-HCT, warranting further development and larger genomic studies where MiHAs are clinically relevant, including cancer immunotherapy, solid organ transplant, and pregnancy.
Comparison of 7 Different Sensors for Detecting Low Respiratory Rates Using a Single Breath Detection Algorithm in Nonintubated, Sedated Volunteers
Authors: Ermer Sean , Brewer Lara , Orr Joe , Egan Talmage D. , Johnson Ken 
Published: September 2018

BACKGROUND:
Numerous technologies are used to monitor respiratory rates in nonintubated patients. No technology has emerged as the standard. The primary aim of this study was to assess the limits of agreement between a reference sensor signal (respiratory inductance plethysmography bands) and 7 alternative sensor signals (nasal capnometer, nasal pressure transducer, oronasal thermistor, abdominal accelerometer, transpulmonary electrical impedance, peritracheal microphone, and photoplethysmography) for measuring low respiratory rates in sedated, nonintubated, supine volunteers. A unified approach based on a single breath detection algorithm was applied to each sensor to facilitate comparison. We hypothesized that all of the sensor signals would allow detection of low (<10 breaths per minute) respiratory rates to within ±2 breaths per minute of the reference sensor signal.

METHODS:
Volunteers received remifentanil and propofol infusions at selected target concentration pairs to induce depression of ventilation. Signals from each sensor were analyzed by an identical threshold-based detection algorithm to compute the breathing rate. Bland-Altman limits of agreement and error rate analyses were used to characterize the performance of each sensor compared to the reference sensor.

RESULTS:
The analysis of the accelerometer and capnometer signals, using Bland-Altman and error rate analyses, showed the highest breath rate agreement (1.96 × standard deviation) of the 7 sensors with −2.1 to 2.2 and −2.5 to 2.7 breaths per minute, respectively. All other signals exhibited wider limits of agreement, with impedance being the widest at −7.8 to 7.4 breaths per minute. For the abdomen accelerometer, 95% of Bland-Altman data points were within ±2 breaths per minute. For the capnometer, 96% of data points were within ±2 breaths per minute. Nasal pressure, thermistor, and microphone all had >80% of data points within ±2 breaths per minute. Impedance and photoplethysmograph signals had 58% and 64%, respectively.

CONCLUSIONS:
A unified approach can be applied to a variety of sensor signals to estimate respiratory rates in spontaneously breathing, nonintubated, sedated volunteers. However, detecting clinically relevant low respiratory rates (<6 breaths per minute) is a technical challenge. By our analysis, no single sensor was able to detect slow respiratory rates with adequate precision (<±2 breaths per minute of the reference signal). Of the sensors evaluated, capnometers and abdominal accelerometers may be the most reliable sensors for identifying hypopnea and central apnea.
Retrospective Cohort Study on the Optimal Timing of Orogastric Tube/Nasogastric Tube Insertion in Infants With Pyloric Stenosis
Authors: Lee Lisa K. , Burns Rebekah A. , Dhamrait Rajvinder S. , Carter Harmony F. , Vadi Marissa G. , Grogan Tristan R. , Elashoff David A. , Applegate Richard L. , Iravani Marc 
Published: September 2018

BACKGROUND:
Hypertrophic pyloric stenosis in infants can cause a buildup of gastric contents. Orogastric tubes (OGTs) or nasogastric tubes (NGTs) are often placed in patients with pyloric stenosis before surgical management to prevent aspiration. However, exacerbation of gastric losses may lead to electrolyte abnormalities that can delay surgery, and placement has been associated with increased risk of postoperative emesis. Currently, there are no evidence-based guidelines regarding OGT/NGT placement in these patients. This study examines whether OGT/NGT placement before arrival in the operating room was associated with a longer time to readiness for surgery as defined by normalization of electrolytes. Secondary outcomes included time from surgery to discharge and ability to tolerate feeds by 6 hours postoperatively in patients with and without early OGT/NGT placement.

METHODS:
In this multicenter retrospective cohort study, data were extracted from the medical records of 481 patients who underwent pyloromyotomy for infantile hypertrophic pyloric stenosis from March 2013 to June 2016. Multivariable linear regression and Cox proportional hazard models were constructed to evaluate the association between placement of an OGT/NGT at the time of admission with increased time to readiness for surgery (defined as the time from admission to the first set of normalized laboratory values) and increased time from surgery to discharge. Multivariable logistic regression was used to evaluate the association between early OGT/NGT placement and the ability to tolerate oral intake at 6 hours postsurgery. Analyses were adjusted for site differences.

RESULTS:
Among patients admitted with electrolyte abnormalities, those with an OGT/NGT placed on presentation required more time until their serum electrolytes were at acceptable levels for surgery by regression analysis (19.2 hours difference; 95% confidence interval, 10.05–28.41; P < .001), after adjusting for site. Overall, patients who had OGTs/NGTs placed before presentation in the operating room had a longer length of stay from surgery to discharge than those without (38.8 hours difference; 95% confidence interval, 25.35–52.31; P < .001), after adjusting for site. OGT/NGT placement before surgery was not associated with failure to tolerate oral intake within 6 hours of surgery after adjusting for site, corrected gestational age, and baseline serum electrolytes.

CONCLUSIONS:
OGT/NGT placement on admission for pyloric stenosis is associated with a longer time to electrolyte correction in infants with abnormal laboratory values on presentation and, subsequently, a longer time until they are ready for surgery. It is also associated with longer postoperative hospital stay but not an increased risk of feeding intolerance within 6 hours of surgical repair.
Spatial positioning of EB family proteins at microtubule tips involves distinct nucleotide-dependent binding properties
Authors: Roth Daniel , Fitton Benjamin P. , Chmel Nikola P. , Wasiluk Natalia , Straube Anne 
Published: September 2018

ABSTRACT
EB proteins track the ends of growing microtubules and regulate microtubule dynamics both directly and by acting as the hub of the tip-tracking network. Mammalian cells express cell type-specific combinations of three EB proteins with different cellular roles. Here, we reconstitute EB1, EB2 and EB3 tip tracking in vitro. We find that all three EBs show rapid exchange at the microtubule tip and that their signal correlates to the microtubule assembly rate. However, the three signals differ in their maxima and position from the microtubule tip. Using microtubules built with nucleotide analogues and site-directed mutagenesis, we show that EB2 prefers binding to microtubule lattices containing a 1:1 mixture of different nucleotides and its distinct binding specificity is conferred by amino acid substitutions at the right-hand-side interface of the EB microtubule-binding domain with tubulin. Our data are consistent with the model that all three EB paralogues sense the nucleotide state of both β-tubulins flanking their binding site. Their different profile of preferred binding sites contributes to occupying spatially distinct domains at the temporally evolving microtubule tip structure.
Smaller clinical trials for decision making; a case study to show p-values are costly
Authors: Graves Nicholas , Barnett Adrian G. , Burn Edward , Cook David 
Published: September 2018

Background: Clinical trials might be larger than needed because arbitrary levels of statistical confidence are sought in the results. Traditional sample size calculations ignore the marginal value of the information collected for decision making. The statistical hypothesis testing objective is misaligned with the goal of generating information necessary for decision-making. The aim of the present study was to show that for a case study clinical trial designed to test a prior hypothesis against an arbitrary threshold of confidence more participants were recruited than needed to make a good decision about adoption. Methods: We used data from a recent RCT powered for traditional rules of statistical significance. The data were also used for an economic analysis to show the intervention led to cost-savings and improved health outcomes. Adoption represented a sensible investment for decision-makers. We examined the effect of reducing the trial’s sample size on the results of the statistical hypothesis-testing analysis and the conclusions that would be drawn by decision-makers reading the economic analysis. Results: As the sample size reduced it became more likely that the null hypothesis of no difference in the primary outcome between groups would fail to be rejected. For decision-makers reading the economic analysis, reducing the sample size had little effect on the conclusion about whether to adopt the intervention. There was always high probability the intervention reduced costs and improved health. Conclusions: Decision makers managing health services are largely invariant to the sample size of the primary trial and the arbitrary p-value of 0.05. If the goal is to make a good decision about whether the intervention should be adopted widely, then that could have been achieved with a much smaller trial. It is plausible that hundreds of millions of research dollars are wasted each year recruiting more participants than required for RCTs.
A literature review on end-of-life care among Korean Americans
Authors: K Park Hye-young , C Hendrix Cristina 
Published: September 2018

Background:The increasing population of Korean Americans in the US makes it mandatory to develop and provide culturally competent end-of-life (EOL) care for this population.Aims:To synthesize previous studies on Korean Americans and their end-of-life (EOL) care.Method:Four databases (Cinahl, PsycInfo, PubMed, and SocIndex) were searched and 11 articles were selected for review.Results:Korean Americans tend to avoid EOL communication, and instead hope that their families would know about their wishes, without discussing them directly. Korean Americans consider advance directives unnecessary, and only a few Korean Americans use advance directives to lessen the burden of their family's decision-making. Many Korean Americans are unaware of what EOL care provides, which may explain why they seldom use it.Conclusion:Providers should discuss EOL care with Korean Americans and tell them what it entails. However, the discussion should be culturally tailored and involve family members whenever possible.
Koping Religius-Spiritual pada Ibu sebagai Caregiver Utama Down Syndrome
Authors: Kurnia Fina Tri 
Published: September 2018

This study aims at understanding the religious spiritual coping experienced by mothers as the main caregiver of down syndrome children. In particular, this study sought for factors influencing the religious spiritual coping and how it was implemented. Subjects in this study were three mothers of children who all had an offspring with down syndrome. Factors affecting their spiritual-religious coping are both internal (e.g. openness, resigned, acceptance, self-efficacy, appreciation of religion) and external (e.g. social support in the community). The implementation of spiritual coping includes a belief that the child is entrusted, an idea that parenting is an effort to gain redemption, gratitude, perseverence, a hope to receive rewards from God. The three informants underwent a perceived change in their views that their financial burden was lifted up, they had the privillege of being close to God, and they surrendered to the control of God, and they had a new perspective of what it means to be happy and strong.[Penelitian ini bertujuan untuk mengetahui koping religius spiritual yang dialami seorang ibu sebagai caregiver utama anak down syndrome. Secara khusus, penelitian ini bertujuan untuk menggali informasi mengenai faktor-faktor yang mempengaruhi koping religius-spiritual dan bagaimana implementasinya. Subjek dalam penelitian ini terdiri dari tiga orang ibu dengan variasi usia anak dengan down syndrome yang diasuhnya, yaitu anak-anak, remaja, dan dewasa. Faktor yang mempengaruhi koping religius-spiritual pada ketiga informan berasal dari faktor internal (terbuka, pasrah, menerima, efikasi diri dan penghayatan agama) dan eksternal (dukungan sosial di lingkungan masyarakat). Implementasi koping religius yakni ritual agama islam (salat, puasa, berdoa) dan hubungan sosial. Sedangkan implementasi koping spiritual yakni keyakinan anak adalah titipan, pengasuhan adalah bagian dari peleburan dosa, kebersyukuran, kesabaran, pengharapan akan pahala dari Tuhan. Mereka mengalami perubahan yang dirasakan berupa pandangan bahwa rizki yang dilancarkan, kenyamanan dekat dengan Tuhan, dan penyerahan kontrol kepada Tuhan, dan transformasi perasaan bahagia dan kuat.]
Validation of Mycobacterium tuberculosis real-time polymerase chain reaction for diagnosis of tuberculous meningitis using cerebrospinal fluid samples: a pilot study
Authors: de Almeida Sérgio M. , Borges Conrado M. , Santana Lucas B. , Golin Gilberto , Correa Lísia , Kussen Gislene B. , Nogueira Keite 
Published: September 2018

Abstract

Background
Timely diagnosis of tuberculous meningitis (TBM) remains challenging. Molecular diagnostic tools are necessary, particularly in low- and middle-income countries. There is no approved commercial polymerase chain reaction (PCR) assay that can be used to detect Mycobacterium tuberculosis in non-respiratory samples, such as the cerebrospinal fluid (CSF). We aimed to validate the threshold cycle (Ct) cut-off points; calculate the operational characteristics of real-time PCR for detection of M. tuberculosis (MTb qPCR) in the CSF; and the inhibitory affect of CSF red blood cells (RBC) and total proteins on MTb qPCR.

Methods
A total of 334 consecutive participants were enrolled. Based on clinical, laboratory and imaging data, cases of suspected TBM were categorized as definite, probable, possible or not TBM cases. Receiver operating characteristic curve analysis was used to select the best discriminating Ct value.

Results
For TBM cases categorized as definite or probable (n=21), the Ct validated for CSF (≤39.5) improved the diagnostic performance of MTb qPCR on CSF samples. The sensitivity was 29%, specificity was 95%, positive predictive value was 26%, negative predictive value was 95%, efficiency was 90% and positive likelihood was 5.3. The CSF RBC and total protein did not affect the positivity of the MTb qPCR.

Conclusions
These data support the validation of a highly specific but low sensitive MTb qPCR assay for the TBM diagnosis using CSF samples. MTb qPCR contributes significantly to the diagnosis, mainly when associated with conventional microbiology tests and clinical algorithms.
21 mesures pour l’enseignement des mathématiques / Der Villani-Torossian-Bericht zum Mathematik-Unterricht in Frankreich
Authors: Agricola Ilka 
Published: September 2018

Zusammenfassung
Der französische Bildungsminister Jean-Michel Blanquer hatte Ende 2017 die Mathematiker
Cédric Villani und Charles Torossian beauftragt, die Probleme des Mathematikunterrichts an
französischen Schulen zu analysieren und Vorschläge zur Verbesserung auszuarbeiten. Sie haben
ihren Bericht und ihre Empfehlungen am 12. Februar 2018 dem Minister überreicht – nicht nur in
Frankreich gibt es seitdem eine intensive Diskussion. Da der Bericht 100 Seiten stark ist und eine
erhebliche Vertrautheit mit dem französischen Schulsystem voraussetzt, präsentieren wir hier einige
Hintergrundfakten sowie eine kommentierte Zusammenfassung, ergänzt durch ein Interview mit
Charles Torossian. Wir hoffen, damit eine breite Grundlage zur Verfügung zu stellen, um konstruktiv
über Ähnlichkeiten und Unterschiede zur Lage in Deutschland diskutieren zu können.