bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiresolution Analyses of Neighborhood Correlates of Crime: Smaller Is Not Better
Authors: Mair Christina , Sumetsky Natalie , Gaidus Andrew , Gruenewald Paul J , Ponicki William R
Published: July 2020

Population analyses of the correlates of neighborhood crime implicitly assume that a single spatial unit can be used to assess neighborhood effects. However, no single spatial unit may be suitable for analyses of the many social determinants of crime. Instead, effects may appear at multiple spatial resolutions, with some determinants acting broadly, others locally, and still others as some function of both global and local conditions. We provide a multiresolution spatial analysis that simultaneously examines US Census block, block group, and tract effects of alcohol outlets and drug markets on violent crimes in Oakland, California, incorporating spatial lag effects at the 2 smaller spatial resolutions. Using call data from the Oakland Police Department from 2010–2015, we examine associations of assaults, burglaries, and robberies with multiple resolutions of alcohol outlet types and compare the performance of single (block-level) models with that of multiresolution models. Multiresolution models performed better than the block models, reflected in improved deviance and Watanabe-Akaike information criteria and well-supported multiresolution associations. By considering multiple spatial scales and spatial lags in a Bayesian framework, researchers can explore multiresolution processes, providing more detailed tests of expectations from theoretical models and leading the way to more effective intervention efforts.
Short-Term but not Long-Term Blood Pressure Variability Is a Predictor of Adverse Cardiovascular Outcomes in Young Untreated Hypertensives
Authors: Saladini Francesca , Fania Claudio , Mos Lucio , Vriz Olga , Mazzer Andrea , Spinella Paolo , Garavelli Guido , Ermolao Andrea , Rattazzi Marcello , Palatini Paolo
Published: July 2020

Background

Whether blood pressure variability (BPV) measured with ambulatory monitoring (short-term BPV) or computed from office visits (long-term BPV) are related to each other and carry similar prognostic information is not well known. We investigated the independent determinants of short-term and long-term BPVs and their predictive capacity for the development of major adverse cardiovascular and renal events (MACEs) in a cohort of young hypertensive participants.

Methods

Long-term BPV was calculated as visit-to-visit SD and average real variability from office blood pressure (BP) measured during 7 visits, within 1 year. Short-term BPV was calculated as weighted 24-hour SD and coefficient of variation. Hazard ratios (HRs) for risk of MACE were computed from multivariable Cox regressions.

Results

1,167 participants were examined; mean age was 33.1 ± 8.5 years. Variables independently associated with 24-hour systolic SD were 24-hour systolic BP, low physical activity, smoking, baseline office pulse pressure, systolic BP dipping, and diastolic white coat effect, while those associated with long-term BPV were mean systolic BP, age, female gender, and baseline office heart rate. During a median follow-up of 17.4 years 75 MACEs occurred. In Cox analysis only short-term BPV resulted a significant predictor of MACE (HR, 1.31 (1.07–1.59); P = 0.0086), while no index of long-term BPV was independently associated with outcome.

Conclusions

In young hypertensive subjects only short-term BPV resulted a significant predictor of MACE on top of traditional ambulatory BP monitoring parameters. Whether reduction of short-term BPV with therapy may reduce the cardiovascular risk independently from the effects on 24-hour BP is a matter for future research.
Trends and Challenges of Telehealth in an Academic Institution: The Unforeseen Benefits of the COVID-19 Global Pandemic
Authors: Wamsley Christine E , Kramer Alan , Kenkel Jeffrey M , Amirlak Bardia
Published: July 2020

The COVID-19 pandemic has necessitated a reorganization of healthcare delivery, shedding light on the many unrealized advantages telehealth has to offer. In addition to facilitating social distancing, minimizing the risk of pathogen exposure, and preserving healthcare resources, there are many benefits of utilizing this platform that can extend beyond the current pandemic, which will change the way healthcare is delivered for generations to come. With the rapid expansion of telehealth, we present data from our high-volume academic institution’s telehealth efforts, with a more focused analysis of plastic surgery. Although state legislation regarding telehealth varies greatly, we discuss challenges such as legal issues, logistical constraints, privacy concerns, and billing. We also discuss various advantages and the future direction of telehealth not only for plastic surgery but also its general utilization for the future of medicine in the United States.
Proteome-scale analysis of phase-separated proteins in immunofluorescence images
Authors: Yu Chunyu , Shen Boyan , You Kaiqiang , Huang Qi , Shi Minglei , Wu Congying , Chen Yang , Zhang Chaolin , Li Tingting
Published: July 2020

Phase separation is an important mechanism that mediates the spatial distribution of proteins in different cellular compartments. While phase-separated proteins share certain sequence characteristics, including intrinsically disordered regions (IDRs) and prion-like domains, such characteristics are insufficient for making accurate predictions; thus, a proteome-wide understanding of phase separation is currently lacking. Here, we define phase-separated proteomes based on the systematic analysis of immunofluorescence images of 12 073 proteins in the Human Protein Atlas. The analysis of these proteins reveals that phase-separated candidate proteins exhibit higher IDR contents, higher mean net charge and lower hydropathy and prefer to bind to RNA. Kinases and transcription factors are also enriched among these candidate proteins. Strikingly, both phase-separated kinases and phase-separated transcription factors display significantly reduced substrate specificity. Our work provides the first global view of the phase-separated proteome and suggests that the spatial proximity resulting from phase separation reduces the requirement for motif specificity and expands the repertoire of substrates. The source code and data are available at https://github.com/cheneyyu/deepphase.
The Russian Drug Reaction Corpus and neural models for drug reactions and effectiveness detection in user reviews
Authors: Tutubalina Elena , Alimova Ilseyar , Miftahutdinov Zulfat , Sakhovskiy Andrey , Malykh Valentin , Nikolenko Sergey
Published: July 2020

Motivation

Drugs and diseases play a central role in many areas of biomedical research and healthcare. Aggregating knowledge about these entities across a broader range of domains and languages is critical for information extraction (IE) applications. To facilitate text mining methods for analysis and comparison of patient’s health conditions and adverse drug reactions reported on the Internet with traditional sources such as drug labels, we present a new corpus of Russian language health reviews.

Results

The Russian Drug Reaction Corpus (RuDReC) is a new partially annotated corpus of consumer reviews in Russian about pharmaceutical products for the detection of health-related named entities and the effectiveness of pharmaceutical products. The corpus itself consists of two parts, the raw one and the labeled one. The raw part includes 1.4 million health-related user-generated texts collected from various Internet sources, including social media. The labeled part contains 500 consumer reviews about drug therapy with drug- and disease-related information. Labels for sentences include health-related issues or their absence. The sentences with one are additionally labeled at the expression level for identification of fine-grained subtypes such as drug classes and drug forms, drug indications and drug reactions. Further, we present a baseline model for named entity recognition (NER) and multilabel sentence classification tasks on this corpus. The macro F1 score of 74.85% in the NER task was achieved by our RuDR-BERT model. For the sentence classification task, our model achieves the macro F1 score of 68.82% gaining 7.47% over the score of BERT model trained on Russian data.

Availability and implementation

We make the RuDReC corpus and pretrained weights of domain-specific BERT models freely available at https://github.com/cimm-kzn/RuDReC.

Supplementary information

Supplementary data are available at Bioinformatics online.
Deuteros 2.0: peptide-level significance testing of data from hydrogen deuterium exchange mass spectrometry
Authors: Lau Andy M , Claesen Jürgen , Hansen Kjetil , Politis Argyris
Published: July 2020

Hydrogen deuterium exchange mass spectrometry (HDX-MS) is becoming increasing routine for monitoring changes in the structural dynamics of proteins. Differential HDX-MS allows comparison of protein states, such as in the absence or presence of a ligand. This can be used to attribute changes in conformation to binding events, allowing the mapping of entire conformational networks. As such, the number of necessary cross-state comparisons quickly increases as additional states are introduced to the system of study. There are currently very few software packages available that offer quick and informative comparison of HDX-MS datasets and even fewer which offer statistical analysis and advanced visualization. Following the feedback from our original software Deuteros, we present Deuteros 2.0 which has been redesigned from the ground up to fulfill a greater role in the HDX-MS analysis pipeline. Deuteros 2.0 features a repertoire of facilities for back exchange correction, data summarization, peptide-level statistical analysis and advanced data plotting features.

Availability and implementation

Deuteros 2.0 can be downloaded for both Windows and MacOS from https://github.com/andymlau/Deuteros_2.0 under the Apache 2.0 license.
lncMat2B regulated by severe hypoxia induces cisplatin resistance by increasing DNA damage repair and tumor-initiating population in breast cancer cells
Authors: García-Venzor Alfredo , Mandujano-Tinoco Edna Ayerim , Ruiz-Silvestre Araceli , Sánchez José Manuel , Lizarraga Floria , Zampedri Cecilia , Melendez-Zajgla Jorge , Maldonado Vilma
Published: July 2020

Multicellular tumor spheroids (MCTSs) constitute a three-dimensional culture system that recapitulates the in vivo tumor microenvironment. Tumor cells cultured as MCTSs present antineoplastic resistance due to the effect of microenvironmental signals acting upon them. In this work, we evaluated the biological function of a new microenvironment-regulated long non-coding RNA, lncMat2B, in breast cancer. In MCTSs, the expression of lncMat2B presented an increase and a zonal heterogeneity, as it was expressed principally in quiescent cells of hypoxic regions of the MCTSs. As expected, functional assays supported the role of severe hypoxia in the regulation of lncMat2B. Moreover, gain- and loss-of-function assays using a transcriptional silencing CRISPR/Cas9 system and gBlock revealed that lncMAT2B regulates the tumor-initiating phenotype. Interestingly, lncMat2B is overexpressed in a cisplatin-resistant MCF-7 cell line, and its ectopic expression in wild type MCF-7 cells increased survival to cisplatin exposure by reducing DNA damage and reactive oxygen species accumulation. lncMAT2B is a possible link between severe hypoxia, tumor-initiating phenotype and drug resistance in breast cancer cells.
Deaths Attributable to Cancer in the US Human Immunodeficiency Virus Population During 2001–2015
Authors: Horner Marie-Josèphe , Shiels Meredith S , Pfeiffer Ruth M , Engels Eric A
Published: July 2020

Background

Antiretroviral therapy (ART) has reduced mortality among people living with human immunodeficiency virus (HIV), but cancer remains an important cause of death. We characterized cancer-attributable mortality in the HIV population during 2001–2015.

Methods

We used data from population-based HIV and cancer registries in the United States (US). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) associating cancer diagnoses with overall mortality. Population-attributable fractions (PAFs) were calculated using these HRs and the proportion of deaths preceded by cancer. Cancer-specific PAFs and cancer-attributable mortality rates were calculated for demographic subgroups, AIDS-defining cancers (Kaposi sarcoma [KS], non-Hodgkin lymphoma [NHL], cervical cancer), and non–AIDS-defining cancers.

Results

Cancer-attributable mortality was 386.9 per 100 000 person-years, with 9.2% and 5.0% of deaths attributed to non–AIDS-defining and AIDS-defining cancers, respectively. Leading cancer-attributable deaths were from NHL (3.5%), lung cancer (2.4%), KS (1.3%), liver cancer (1.1%), and anal cancer (0.6%). Overall, cancer-attributable mortality declined from 484.0 per 100 000 person-years during 2001–2005 to 313.6 per 100 000 person-years during 2011–2015, while the PAF increased from 12.6% to 17.1%; the PAF for non–AIDS-defining cancers increased from 7.2% to 11.8% during 2011–2015. Cancer-attributable mortality was highest among those aged ≥60 years (952.2 per 100 000 person-years), with 19.0% of deaths attributed to non–AIDS-defining cancers.

Conclusions

Although cancer-attributable mortality has declined over time, it remains high and represents a growing fraction of deaths in the US HIV population. Mortality from non–AIDS-defining cancers may rise as the HIV population ages. ART access, early cancer detection, and improved cancer treatment are priorities for reducing cancer-attributable mortality.
Vancomycin Area Under the Curve to Predict Timely Clinical Response in the Treatment of Methicillin-resistantStaphylococcus aureusComplicated Skin and Soft Tissue Infections
Authors: Alosaimy Sara , Murray Kyle P , Zasowski Evan J , Morrisette Taylor , Lagnf Abdalhamid M , Lodise Thomas P , Rybak Michael J
Published: July 2020

Introduction

Although recent guidelines have recommended monitoring vancomycin (VAN) area under the curve (AUC)/minimum inhibitory concentration (MIC) to ensure clinical efficacy and minimize toxicity in methicillin-resistant Staphylococcus aureus (MRSA) for various infections, there are no recommendations regarding complicated skin and soft tissue infections (cSSTIs). We aimed to evaluate the association between VAN AUC and clinical outcomes in MRSA cSSTIs.

Methods

This was a retrospective cohort study of adult patients treated with ≥72 hours of VAN for MRSA cSSTI from 2008 to 2013 at Detroit Medical Center. The primary outcome was timely clinical success (TCS) defined as (1) resolution of signs and symptoms of infection within 72 hours, (2) stabilization and/or reduction in lesion size, (3) alternative agents not required due to VAN failure or toxicity as elected by the prescribing clinician. Classification and regression tree (CART) analysis was performed to determine the AUC associated with TCS in the cohort. Multivariable logistic regression was used to evaluate the association between VAN-AUC and the primary outcome.

Results

A total of 154 patients were included in this analysis. CART identifed an AUC ≥435 mg*hr/L for TCS. Overall, 60.9% of patients experienced TCS; 69.7% in the target-AUC group versus 52.5% in the below-target AUC group, (P = .013). Target-AUC attainment was independently associated with increased odds of TCS (adjusted odds ratio [aOR], 2.208; 95% confidence interval [CI], 1.047–4.659).

Conclusions

In adults treated with VAN for MRSA cSSTI, target-AUC attainment was independently associated with improved clinical outcomes and maybe most warranted for patients at high risk of VAN failure or VAN-associated toxicity.
Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care
Authors: Olender Susan A , Perez Katherine K , Go Alan S , Balani Bindu , Price-Haywood Eboni G , Shah Nirav S , Wang Su , Walunas Theresa L , Swaminathan Shobha , Slim Jihad , Chin BumSik , De Wit Stéphane , Ali Shamim M , Soriano Viladomiu Alex , Robinson Philip , Gottlieb Robert L , Tsang Tak Yin Owen , Lee I-Heng , Hu Hao , Haubrich Richard H , Chokkalingam Anand P , Lin Lanjia , Zhong Lijie , Bekele B Nebiyou , Mera-Giler Robertino , Phulpin Chloé , Edgar Holly , Gallant Joel , Diaz-Cuervo Helena , Smith Lindsey E , Osinusi Anu O , Brainard Diana M , Bernardino Jose I ,   GS-US-540–5773 and GS-US-540–5807 Investigators
Published: July 2020

Background

We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care.

Methods

GS-US-540–5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540–5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality.

Results

After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34–3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22–.68, P = .001).

Conclusions

In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19.

Clinical Trials Registration

NCT04292899 and EUPAS34303.
Bacillus Calmette-Guérin (BCG) Infections at High Frequency in Both AR-CGD and X-CGD Patients Following BCG Vaccination
Authors: Ishikawa Takashi , Okai Masashi , Mochizuki Emi , Uchiyama Toru , Onodera Masafumi , Kawai Toshinao
Published: July 2020

Background

Patients with chronic granulomatous disease (CGD) develop severe infections, including Bacillus Calmette-Guérin (BCG). Although the autosomal recessive CGD (AR-CGD) patients should hypothetically develop relatively fewer infections compared to the X-linked CGD (X-CGD) patients due to more residual reactive oxygen intermediates, the impacts of BCG vaccination on AR-CGD and X-CGD patients are unclear. Herein, we demonstrated the clinical features of BCG infections, treatments, and genetic factors in CGD patients after BCG vaccination under the Japanese immunization program.

Methods

We collected data retrospectively from 43 patients with CGD and assessed their history of initial infection, age at diagnosis of CGD, BCG vaccination history, clinical course, treatment for BCG infections, and genetic mutations associated with CGD.

Results

Fourteen CGD patients avoided BCG vaccination because of other preceding infections and family history. Of 29 patients with CGD who received BCG vaccination, 20 patients developed BCG infections. Although the age at onset of initial infection in X-CGD patients was significantly younger than that in AR-CGD patients (P < .01), the onset and frequency of BCG infections were similar in X-CGD and AR-CGD patients. In X-CGD patients, BCG infections equally developed in the patients carrying missense, insertion, deletion, nonsense, and splice mutations of CYBB. All CGD patients with BCG infections were successfully treated with anti-tuberculous drugs.

Conclusions

Although X-CGD patients develop severe infections at a younger age than AR-CGD patients, our data suggested that BCG infections develop at high frequency in both AR-CGD and X-CGD patients, regardless of genotype and mutant forms.
Cost-effectiveness of Preemptive Therapy Versus Prophylaxis in a Randomized Clinical Trial for the Prevention of Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors
Authors: Singh Nina , Winston Drew J , Razonable Raymund R , Lyon G Marshall , Silveira Fernanda P , Wagener Marilyn M , Limaye Ajit P
Published: July 2020

Background

The relative costs of preemptive therapy (PET) or prophylaxis for the prevention of cytomegalovirus (CMV) disease in high-risk donor CMV-seropositive/recipient-seronegative (D+/R−) liver transplant recipients have not been assessed in the context of a randomized trial.

Methods

A decision tree model was constructed based on the probability of outcomes in a randomized controlled trial that compared valganciclovir as PET or prophylaxis for 100 days in 205 D+/R− liver transplant recipients. Itemized costs for each site were obtained from a federal cost transparency database. Total costs included costs of implementation of the strategy and CMV disease treatment-related costs. Net cost per patient was estimated from the decision tree for each strategy.

Results

PET was associated with a 10% lower absolute rate of CMV disease (9% vs 19%). The cost of treating a case of CMV disease in our patients was $88 190. Considering cost of implementation of strategy and treatment-related cost for CMV disease, the net cost-savings per patient associated with PET was $8707 compared to prophylaxis. PET remained cost-effective across a range of assumptions (varying costs of monitoring and treatment, and rates of disease).

Conclusions

PET is the dominant CMV prevention strategy in that it was associated with lower rates of CMV disease and lower overall costs compared to prophylaxis in D+/R− liver transplant recipients. Costs were driven primarily by more hospitalizations and higher CMV disease–associated costs due to delayed onset postprophylaxis disease in the prophylaxis group.
Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study
Authors: Jeong Han Eol , Lee Hyesung , Shin Hyun Joon , Choe Young June , Filion Kristian B , Shin Ju-Young
Published: July 2020

Background

Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells.

Methods

We conducted a cohort study using South Korea’s nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding.

Results

Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13–2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96–2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49–4.14).

Conclusions

While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.
Navigating Clinical Utilization of Direct-from-Specimen Metagenomic Pathogen Detection: Clinical Applications, Limitations, and Testing Recommendations
Authors: Filkins Laura M , Bryson Alexandra L , Miller Steve A , Mitchell Stephanie L
Published: July 2020

Background

Metagenomic next generation sequencing (mNGS) is becoming increasingly available for pathogen detection directly from clinical specimens. These tests use target-independent, shotgun sequencing to detect potentially unlimited organisms. The promise of this methodology to aid infection diagnosis is demonstrated through early case reports and clinical studies. However, the optimal role of mNGS in clinical microbiology remains uncertain.

Content

We reviewed studies reporting clinical use of mNGS for pathogen detection from various specimen types, including cerebrospinal fluid, plasma, lower respiratory specimens, and others. Published clinical study data were critically evaluated and summarized to identify promising clinical indications for mNGS-based testing, to assess the clinical impact of mNGS for each indication, and to recognize test limitations. Based on these clinical studies, early testing recommendations are made to guide clinical utilization of mNGS for pathogen detection. Finally, current barriers to routine clinical laboratory implementation of mNGS tests are highlighted.

The promise of direct-from-specimen mNGS to enable challenging infection diagnoses has been demonstrated through early clinical studies of patients with meningitis or encephalitis, invasive fungal infections, community acquired pneumonia, and other clinical indications. However, the proportion of patient cases with positive clinical impact due to mNGS testing is low in published studies and the cost of testing is high, emphasizing the importance of improving our understanding of ‘when to test’ and for which patients mNGS testing is appropriate.
Long-Term Clinical Effectiveness of Ustekinumab in Patients With Crohn’s Disease: A Retrospective Cohort Study
Authors: Ito Takahiro , Maemoto Atsuo , Katsurada Takehiko , Tanaka Hiroki , Motoya Satoshi , Ueno Nobuhiro , Fujiya Mikihiro , Ashida Toshifumi , Hirayama Daisuke , Nakase Hiroshi
Published: July 2020

Background

This study clarifies the long-term effectiveness of ustekinumab based on real-life data from Japanese Crohn’s disease (CD) patients.

Methods

A total of 137 patients were included, and 124 patients (90.5%) were exposed to anti-tumor necrosis factor-α agents.

Results

The clinical remission rate at week 52 was 32.4% in moderate to severely active CD patients. The achievement of clinical remission for 8 weeks after ustekinumab therapy induction was associated with clinical remission at week 52. Ustekinumab persistence rate at week 104 was 81.4%.

Conclusion

Ustekinumab is effective and persistent in CD patients with the previous treatment history of several biologics.
Microscopic Colitis and Risk Of Cancer—AA Population-Based Cohort Study
Authors: Bergman David , Khalili Hamed , Roelstraete Bjorn , Ludvigsson Jonas F
Published: July 2020

Background and Aims

The association between microscopic colitis [MC] and cancer risk is unclear. Large, population-based studies are lacking.

Methods

We conducted a nationwide cohort study of 11 758 patients with incident MC [diagnosed 1990–2016 in Sweden], 50 828 matched reference individuals, and 11 614 siblings to MC patients. Data were obtained through Sweden´s pathology departments and from the Swedish Cancer Register. Adjusted hazard ratios [aHRs] were calculated using Cox proportional hazards models.

Results

At the end of follow-up [mean: 6.7 years], 1239 [10.5%] of MC patients had received a cancer diagnosis, compared with 4815 [9.5%] of reference individuals (aHR 1.08 [95% confidence interval1.02–1.16]). The risk of cancer was highest during the first year of follow up. The absolute excess risks for cancer at 5, 10, and 20 years after MC diagnosis were + 1.0% (95% confidence interval [CI] 0.4%-1.6%), +1.5% [0.4%-2.6%], and + 3.7% [-2.3–9.6%], respectively, equivalent to one extra cancer event in every 55 individuals with MC followed for 10 years. MC was associated with an increased risk of lymphoma (aHR 1.43 [1.06–1.92]) and lung cancer (aHR 1.32 [1.04–1.68]) but with decreased risks of colorectal (aHR 0.52 [0.40–0.66]) and gastrointestinal cancers (aHR 0.72 [0.60–0.85]). We found no association with breast or bladder cancer. Using siblings as reference group to minimise the impact of shared genetic and early environmental factors, patients with MC were still at an increased risk of cancer (HR 1.20 [1.06–1.36]).

Conclusions

This nationwide cohort study demonstrated an 8% increased risk of cancer in MC patients. The risk was highest during the first year of follow-up.
Endoscopic Submucosal Dissection for Visible Dysplasia Treatment in Ulcerative Colitis Patients: Cases Series and Systematic Review of Literature
Authors: Manta Raffaele , Zullo Angelo , Telesca Donato Alessandro , Castellani Danilo , Germani Ugo , Reggiani Bonetti Luca , Conigliaro Rita , Galloro Giuseppe
Published: July 2020

Background and Aims

Ulcerative colitis [UC] patients are at an increased risk of developing colorectal cancer due to chronic inflammation. Endoscopic submucosal dissection [ESD] allows removal of non-invasive neoplastic lesions in the colon, but few data are available on its efficacy in UC patients.

Methods

Data from consecutive UC patients diagnosed with visible dysplastic lesions in the colon who underwent ESD were evaluated. The en bloc removal, R0 resection and complication rates were calculated. Local recurrence and metachronous lesions during follow-up were identified. A systematic review of the literature with pooled data analysis was performed.

Results

A total of 53 UC patients [age: 65 years; range 30–74; M/F: 31/22] underwent ESD. The en bloc resection rate was 100%, and the R0 resection rate was 96.2%. Bleeding occurred in seven [13.2%] patients, and perforation in three [5.6%] cases, all treated at endoscopy. No recurrence was observed, but two metachronous lesions were detected. Data from six other studies [three Asian and three European] were available. By pooling data, en bloc resection was successful in 88.4% (95% confidence interval [CI] = 83.5–92) of 216 lesions and in 91.8% [95% CI = 87.3–94.8] of 208 patients. R0 resection was achieved in 169 ESDs, equivalent to a 78.2% [95% CI = 72.3–83.2] rate for lesions and 81.3% [95% CI = 75.4–86] rate for patients. No difference between European and Asian series was noted.

Conclusions

This pooled data analysis indicated that ESD is a suitable tool for safely and properly removing non-invasive neoplastic lesions on colonic mucosa of selected UC patients.
Relationship between arterial remodelling and serial changes in coronary atherosclerosis by intravascular ultrasound: an analysis of the IBIS-4 study
Authors: Koskinas Konstantinos C. , Maldonado Rafaela , Garcia-Garcia Hector M. , Yamaji Kyohei , Taniwaki Masanori , Ueki Yasushi , Otsuka Tatsuhiko , Zanchin Christian , Karagiannis Alexios , Radu Juul Jensen Maria D. , Losdat Sylvain , Zaugg Serge , Windecker Stephan , Räber Lorenz
Published: July 2020

Aims

Arterial remodelling is an important determinant of coronary atherosclerosis. Assessment of the remodelling index, comparing a lesion to a local reference site, is a suboptimal correlate of serial vascular changes. We assessed a novel approach which, unlike the local-reference approach, uses the entire artery’s global remodelling as reference.

Methods and results

Serial (baseline and 13 months) intravascular ultrasound was performed in 146 non-infarct-related arteries of 82 patients treated with high-intensity statin. Arteries were divided into 3-mm segments (n = 1479), and focal remodelling was characterized in individual segments at both timepoints applying the global arterial reference approach. First, we compared preceding vascular changes in relation to follow-up remodelling. Second, we examined whether baseline remodelling predicts subsequent plaque progression/regression. At follow-up, segments with constrictive vs. compensatory or expansive remodelling had greater preceding reduction of vessel area (−0.67 vs. −0.38 vs. −0.002 mm2; P < 0.001) and lumen area (−0.82 vs. −0.09 vs. 0.40 mm2; P < 0.001). Overall, we found significant regression in percent atheroma volume (PAV) [−0.80% (−1.41 to −0.19)]. Segments with constrictive remodelling at baseline had greater subsequent PAV regression vs. modest regression in the compensatory, and PAV progression in the expansive remodelling group (−6.14% vs. −0.71% vs. 2.26%; P < 0.001). Lesion-level analyses (n = 118) showed no differences when remodelling was defined by the local reference approach at baseline or follow-up.

Conclusion

Remodelling assessment using a global arterial reference approach, but not the commonly used, local reference site approach, correlated reasonably well with serial changes in arterial dimensions and identified arterial segments with subsequent PAV progression despite intensive statin treatment and overall atheroma regression.
Growth of hypoplastic mitral valves in hypoplastic left heart complex and similar constellations after anatomical left superior vena cava correction
Authors: Cesnjevar Robert A , Harig Frank , Dietz Moritz , Alkassar Muhannad , Waellisch Wolfgang , Rueffer André , Dittrich Sven , Purbojo Ariawan
Published: July 2020

OBJECTIVES

Left superior vena cava (LSVC)-related obstruction of mitral inflow is a rare finding in patients with complex cardiac anomalies like hypoplastic left heart complex. We report our experience by establishing a left superior to right superior caval vein continuity (innominate vein creation by direct LSVC–right superior vena cava end-to-side-anastomosis), and coronary sinus unroofing if indicated for LSVC-related mitral inflow obstruction.

METHODS

Nineteen patients (median age: 1.0 ± 0.3 years; range: 7 days–4.8 years) underwent anatomical correction of LSVC without the use of foreign material in conjunction with repair or palliation of congenital anomalies in a single centre between April 2015 and November 2019. Indications for the procedure were LSVC-related obstruction of left ventricular inflow due to a dilated coronary sinus. Additional procedures included mitral (n = 7) or atrioventricular (n = 3) valve surgery, right ventricular to pulmonary artery conduit (n = 3), first stage palliation (n = 3) or biventricular repair (n = 5) of hypoplastic left heart complex. Three patients needed secondary mitral valve replacement (n = 3).

RESULTS

All LSVC or coronary sinus-related obstructions were effectively relieved. No patient died early, 2 patients died late after the procedure. One patient needed stenting of the superior vena cava below the unobstructed cephalad vein anastomosis at the former right superior vena cava-cannulation-site. Follow-up was complete and demonstrated an 89.5% survival after 2.5 ± 0.4 years. Innominate vein patency was 100% documented by echocardiography (n = 19), cardiac catheterization (n = 6) or both. Mean mitral valve z-scores before the operation were −1.7 ± 0.2 (range −3.8 to 0.3) and increased to 0.7 ± 0.2 (range −0.7 to 1.9) after LSVC repair.

CONCLUSIONS

Anatomical correction by surgical creation of an innominate vein is an effective method to relieve LSVC-related obstructions and promotes mitral valvar growth. Mitral ring sizes were at least normalized after surgery at the time of discharge. Further prospective follow-up studies to evaluate the growth potential of left-sided heart structures by reporting cardiac z-scores are needed to evaluate the true impact of coronary sinus unroofing.
Pregnancy-associated idiopathic laryngotracheal stenosis: presentation, management and results of surgical treatment
Authors: Tapias Luis F. , Rogan Thomas J. , Wright Cameron D. , Mathisen Douglas J.
Published: July 2020

OBJECTIVES

Idiopathic laryngotracheal stenosis (ILTS) is an uncommon problem arising mostly in women. In some, it arises during or is exacerbated by pregnancy. Experience with management of patients with this rare association is limited. This study seeks to evaluate the management of patients with pregnancy-associated ILTS and compare outcomes to cases not associated with pregnancy.

METHODS

Retrospective review of 15 patients undergoing surgical treatment of pregnancy-associated ILTS from 1971 to 2013. Variables of interest and airway outcomes were compared to patients with non-pregnancy-associated ILTS.

RESULTS

Pregnancy-associated ILTS was observed in 15/263 (5.7%) patients. Symptoms developed during their first pregnancy. When compared to non-pregnancy patients, these patients were younger (37 vs 47 years; P = 0.0003), had more prior tracheostomies (26.7% vs 10.9%; P = 0.085) and had more preoperative airway dilatations (86.7% vs 57.7%; P = 0.030). All patients completed pregnancy without complications and ultimately underwent laryngotracheal resection. The expression of hormonal receptors in the surgical specimens was similar in both groups (oestrogen receptors: 100% vs 75% and progesterone receptors: 71.4% vs 72.1%, in pregnancy and non-pregnancy patients, respectively). Airway outcomes were good/excellent in 13 (86.7%) patients with pregnancy-associated ILTS and 225 (90.7%) patients without pregnancy association (P = 0.642), and did not change when adjusting for other risk factors.

CONCLUSIONS

Pregnancy-associated ILTS is rare. The pathophysiology is unclear, but appearance of symptoms during pregnancy may suggest hormonal factors. To minimize foetal risk, dilatation during pregnancy followed by laryngotracheal resection after delivery is the preferred treatment. Pregnancy association does not seem to affect outcomes with expected satisfactory results in most patients.
The role of research synthesis in facilitating research–pedagogy dialogue
Authors: Chong Sin Wang
Published: July 2020

Readers Respond is a forum for individuals to contribute their own reactions, perspectives, or experiences in relation to a specific article or articles published in a recent issue of ELT Journal. These views are not necessarily those of the Editor, the Editorial Panel, or the Publisher. This article responds to Sato, M. and S. Loewen 2019 ‘Do teachers care about research? The research–pedagogy dialogue’. ELT Journal 73/1: 1–10.
Post-operative cardiac implantable electronic devices in patients undergoing cardiac surgery: a contemporary experience
Authors: Waddingham Peter Henry , Behar Jonathan M , Roberts Neil , Dhillon Gurpreet , Graham Adam J , Hunter Ross J , Hayward Carl , Dhinoja Mehul , Muthumala Amal , Uppal Rakesh , Rowland Edward , Earley Mark J , Schilling Richard J , Sporton Simon , Lowe Martin , Harky Amer , Segal Oliver R , Lambiase Pier D , Chow Anthony W C
Published: July 2020

Aims

Optimum timing of pacemaker implantation following cardiac surgery is a clinical challenge. European and American guidelines recommend observation, to assess recovery of atrioventricular block (AVB) (up to 7 days) and sinus node (5 days to weeks) after cardiac surgery. This study aims to determine rates of cardiac implantable electronic devices (CIEDs) implants post-surgery at a high-volume tertiary centre over 3 years. Implant timing, patient characteristics and outcomes at 6 months including pacemaker utilization were assessed.

Methods and results

All cardiac operations (n = 5950) were screened for CIED implantation following surgery, during the same admission, from 2015 to 2018. Data collection included patient, operative, and device characteristics; pacing utilization and complications at 6 months. A total of 250 (4.2%) implants occurred; 232 (3.9%) for bradycardia. Advanced age, infective endocarditis, left ventricle systolic impairment, and valve surgery were independent predictors for CIED implants (P < 0.0001). Relative risk (RR) of CIED implants and proportion of AVB increased with valve numbers operated (single–triple) vs. non-valve surgery: RR 5.4 (95% CI 3.9–7.6)–21.0 (11.4–38.9) CIEDs. Follow-up pacing utilization data were available in 91%. Significant utilization occurred in 82% and underutilization (<1% A and V paced) in 18%. There were no significant differences comparing utilization rates in early (≤day 5 post-operatively) vs. late implants (P = 0.55).

Conclusion

Multi-valve surgery has a particularly high incidence of CIED implants (14.9% double, 25.6% triple valve). Age, left ventricle systolic impairment, endocarditis, and valve surgery were independent predictors of CIED implants. Device underutilization was infrequent and uninfluenced by implant timing. Early implantation (≤5 days) should be considered in AVB post-multi-valve surgery.
Non-vitamin K oral anticoagulants and risk of fractures: a systematic review and meta-analysis
Authors: Mongkhon Pajaree , Fanning Laura , Wong Kirstie H T W , Man Kenneth K C , Wong Ian C K , Lau Wallis C Y
Published: July 2020

Aims 

Comparative fracture risk for non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) among patients with atrial fibrillation (AF) remains unclear. This study aimed to provide summary relative risk (RR) estimates for associations between NOACs vs. VKAs and fracture risk.

Methods and results 

PubMed, EMBASE, and Cochrane Library were searched from 2010 to 26 May 2020. Observational studies investigating the association between NOACs vs. VKAs and fracture risk in patients with AF were included. The adjusted effect estimates were pooled using the DerSimonian–Laird random effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiological (MOOSE) guidelines were followed. Five observational studies comprising 269 922 patients and 4289 fractures were included. Non-vitamin K antagonist oral anticoagulants use was associated with a lower risk of any fractures compared to VKAs use, with moderate heterogeneity [pooled RR = 0.83, 95% confidence interval (CI): 0.75–0.92, P < 0.001, I2 = 73.0%]. When comparing individual NOAC to VKAs, a statistically significant lower risk of any fractures was found for rivaroxaban (pooled RR = 0.79, 95% CI: 0.71–0.88, P < 0.001, I2 = 55.2%) and apixaban (pooled RR = 0.75, 95% CI: 0.60–0.92, P = 0.007, I2 = 54.5%), but not dabigatran (pooled RR = 0.87, 95% CI: 0.74–1.01, P = 0.061, I2 = 74.6%). No differences were observed in all head-to-head comparisons between NOACs.

Conclusion 

This large meta-analysis suggests that NOACs use was associated with a lower risk of fractures compared with VKAs. Fracture risks were similar between NOACs. These findings may help inform the optimal anticoagulant choice for patients with AF at high risk of fracture.
The importance of teamwork climate for preventing burnout in UK general practices
Authors: Galleta-Williams Henry , Esmail Aneez , Grigoroglou Christos , Zghebi Salwa S , Zhou Anli Yue , Hodkinson Alexander , Panagioti Maria
Published: July 2020

This short report aims to investigate the association between teamwork and burnout among general practitioners (GPs). A two-stage survey was conducted. In stage one, validated self-report measures of burnout and teamwork were completed by 50 GPs across 12 general practices in Greater Manchester, UK. In stage two, staff members across 3 of the 12 general practices (GPs, nursing staff, managers and admin staff) responded to free text questions about teamwork (n = 20). The results of the stage one survey showed that teamwork in GPs was significantly negatively associated with the emotional exhaustion (r = −0.326, P < 0.05) and depersonalization (r = −0.421, P < 0.01) domains of the burnout measure and significantly positively associated with the personal accomplishment (r = 0.296, P < 0.05) domain. Free text responses in stage two were assigned into three themes: (i) addressing organizational barriers which might threaten teamwork, (ii) promoting the view of teamwork as a shared responsibility among all staff members of the general practice and (iii) implementing improvement strategies which can be embedded in the busy environment of general practices. GPs and other staff members of general practices valued the importance of teamwork for boosting their morale and mitigating burnout. Future research should focus on designing and embedding brief teamwork improvement strategies in general practices.
Sleep timing and hygiene practices of high bedtime procrastinators: a direct observational study
Authors: Zhu Liwei , Meng Dexin , Ma Xiaohan , Guo Jing , Mu Li
Published: July 2020

Background

Bedtime procrastination (BP) has been proven to be an important indicator of sleep insufficiency from a psychological perspective. However, the effect of BP on sleep patterns related to sleep deficiency remains unknown.

Objective

This study aimed to investigate the characteristics of self-reported sleep timing and hygiene practices between high and low-moderate bedtime procrastinators. It also aimed to examine the relationship between these characteristics and high level of BP.

Methods

A total of 391 Chinese college students were recruited for this study. Participants completed questionnaires on demographics, sleep timing variables, the Sleep Hygiene Practice Scale (SHPS) and the Bedtime Procrastination Scale (BPS).

Results

High bedtime procrastinators were more likely to have higher SHPS global and subdomain scores (Ps < 0.001). They also were more likely to exhibit later sleep onset, sleep offset and rise time on both weekdays and weekends (Ps < 0.01). The significant independent determinant factors of the prevalence of high BP were: SHPS total score [odds ratio (OR) = 1.05, P < 0.001], arousal-related behaviour (OR = 1.07, P = 0.007), sleep schedule and timing (OR = 1.12, P < 0.001) and sleep onset on weekdays (OR = 2.65, P < 0.001).

Conclusions

High bedtime procrastinators showed maladaptive sleep-related variables, which mainly manifested as changes in arousal-related behaviour and sleep schedule and timing, as well as delays in sleep onset time on weekdays. The findings could help guide the formulation of appropriate interventions in primary health care.