bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 2 study of all‐oral ixazomib, cyclophosphamide and low‐dose dexamethasone for relapsed/refractory multiple myeloma
Authors: Kumar Shaji K. , Grzasko Norbert , Delimpasi Sosana , Jedrzejczak Wieslaw W. , Grosicki Sebastian , Kyrtsonis Marie‐Christine , Spencer Andrew , Gupta Neeraj , Teng Zhaoyang , Byrne Catriona , Labotka Richard , Dimopoulos Meletios A.
Published: November 2018

There is a need for efficacious, convenient treatments with long‐term tolerability for patients with relapsed/refractory multiple myeloma (RRMM). This phase 2 study evaluated the all‐oral combination of ixazomib, cyclophosphamide and dexamethasone (ICd). Patients with RRMM received ixazomib 4 mg and cyclophosphamide 300 mg/m2 on days 1, 8 and 15, and dexamethasone 40 mg on days 1, 8, 15 and 22 in 28‐day cycles. The primary endpoint was overall response rate (ORR). Seventy‐eight patients were enrolled (median age 63·5 years). At data cut‐off, patients had received a median of 12 treatment cycles; 31% remained on treatment. ORR was 48% [16% very good partial response or better (≥VGPR)]. ORR was 64% and 32% in patients aged ≥65 and <65 years (25% and 16% ≥VGPR), respectively. At a median follow‐up of 15·2 months, median progression‐free survival (PFS) was 14·2 months, with a trend towards better PFS in patients aged ≥65 years vs. <65 years (median 18·7 months vs. 12·0 months; hazard ratio 0·62, P = 0·14). ICd was well tolerated. The most common treatment‐emergent adverse events were diarrhoea (33%), nausea (24%), upper respiratory tract infection (24%), and thrombocytopenia (22%); 10 patients (13%) had peripheral neuropathy (one grade 3). This study is registered at ClinicalTrials.gov (NCT02046070).
Impact of parental asthma, prenatal maternal asthma control, and vitamin D status on risk of asthma and recurrent wheeze in 3‐year‐old children
Authors: Mirzakhani Hooman , Carey Vincent J. , Zeiger Robert , Bacharier Leonard B. , O'Connor George T. , Schatz Michael X. , Laranjo Nancy , Weiss Scott T. , Litonjua Augusto A.
Published: November 2018

Background

While familial clustering of asthma is known, few studies have reported on the relative roles of paternal and maternal asthma and the role of maternal asthma control in pregnancy on the risk for asthma in the child.

Objective

We aimed to investigate the relative roles of paternal asthma, maternal asthma, and maternal asthma control during pregnancy on the risk of asthma or recurrent wheeze in 3‐year‐old children and how prenatal and cord blood vitamin D status might affect this risk.

Methods

Data from 806 women, their partners (biologic fathers of the infants), and their children participated in the Vitamin D Antenatal Asthma Reduction Trail (VDAART, clinicaltrials.gov identification number NCT00920621) were used for this cohort analysis. The parental report of physician‐diagnosed asthma or recurrent wheeze in offspring was the main outcome. Weibull regression models for interval‐censored event times were used to estimate the main variables of interests and additional covariates on the outcome.

Results

The highest risk was observed among children with both parents being asthmatic relative to non‐asthmatic parents (aHR = 2.30, 95% CI: 1.35‐3.84), and less so if only the mother was asthmatic (aHR = 1.70, 95% CI: 1.17‐2.40). In the subset of children born to asthmatic mothers, the risk for asthma was higher in those who were born to mothers whose asthma was uncontrolled (aHR = 1.60, 95% CI: 1.02‐2.54). Children whose mothers had sufficient vitamin D status (25Hydroxyvitamin D ≥ 30 ng/mL) at early and late pregnancy and had cord blood vitamin D sufficiency demonstrated a lower risk of asthma/recurrent wheeze than children who had insufficient cord blood vitamin D status at birth (aHR = 0.47, 95% CI: 0.27‐0.83).

Conclusion and Clinical Relevance

Careful attention to maternal asthma control, monitoring vitamin D status, and correcting insufficiency at early pregnancy and maintaining the sufficiency status throughout pregnancy have potential preventive roles in offspring asthma or recurrent wheeze.
Forecast skill for predicting distribution shifts: A retrospective experiment for marine fishes in the Eastern Bering Sea
Authors: Thorson James T.
Published: November 2018

Forecasting distribution shifts under novel environmental conditions is a major task for ecologists and conservationists. Researchers forecast distribution shifts using several tools including: predicting from an empirical relationship between a summary of distribution (population centroid) and annual time series (“annual regression,” AR); or fitting a habitat‐envelope model to historical distribution and forecasting given predictions of future environmental conditions (“habitat envelope,” HE). However, surprisingly little research has estimated forecast skill by fitting to historical data, forecasting distribution shifts and comparing forecasts with subsequent observations of distribution shifts. I demonstrate the important role of retrospective skill testing by forecasting poleward movement over 1‐, 2‐ or 3‐year periods for 20 fish and crab species in the Eastern Bering Sea and comparing forecasts with observed shifts. I specifically introduce an alternative vector‐autoregressive spatio‐temporal (VAST) forecasting model, which can include species temperature responses, and compare skill for AR, HE and VAST forecasts. Results show that the HE forecast has 30%–43% greater variance than predicting that future distribution is identical to the estimated distribution in the final year (a “persistence” forecast). Meanwhile, the AR explains 2%–6% and VAST explains 8%–25% of variance in poleward movement, and both have better performance than a persistence forecast. HE and AR both generate forecast intervals that are too narrow, while VAST models with or without temperature have appropriate width for forecast intervals. Retrospective skill testing for more regions and taxa should be used as a test bed to guide future improvements in methods for forecasting distribution shifts.
Female variation in allocation of steroid hormones, antioxidants and fatty acids: a multilevel analysis in a wild passerine bird
Authors: Mentesana Lucia , Isaksson Caroline , Goymann Wolfgang , Andersson Martin N. , Trappschuh Monika , Hau Michaela
Published: November 2018

The environment where an embryo develops can be influenced by components of maternal origin, which can shape offspring phenotypes and therefore maternal fitness. In birds that produce more than one egg per clutch, females differ in the concentration of components they allocate into the yolk along the laying sequence. However, identification of processes that shape female yolk allocation and thus offspring phenotype still remains a major challenge within evolutionary ecology. A way to increase our understanding is by acknowledging that allocation patterns can differ depending on the level of analysis, such as the population versus the among‐female (within‐population) level. We employed mixed models to analyze at both levels the variation in allocation along the laying sequence of four steroid hormones, three antioxidants, and four groups of fatty acids present in the egg yolks of wild great tits Parus major. We also quantified repeatabilities for each component to study female consistency. At a population level, the concentrations/proportions of five yolk components varied along the laying sequence, implying that the developmental environment is different for offspring developing in first versus last eggs. Females varied substantially in the mean allocation of components and in their plasticity along the laying sequence. For most components, these two parameters were negatively correlated. Females were also remarkably repeatable in their allocation. Overall, our data emphasize the need to account for female variation in yolk allocation along the laying sequence at multiple levels, as variation at a population level is underpinned by different individual patterns. Our findings also highlight the importance of considering both levels of analysis in future studies investigating the causes and fitness consequences of yolk compounds. Finally, our results on female repeatability confirm that analyzing one egg per nest is a suitable way to address the consequences of yolk resource deposition for the offspring.
A unifying framework for improving health care
Authors: Djulbegovic Benjamin , Bennett Charles L. , Guyatt Gordon
Published: November 2018

The quality health care around world is suboptimal. To improve the quality of contemporary health care delivery, advocates have proposed a number of scientific and technical initiatives. All these initiatives, however, have arisen and continue to operate in siloes, resulting in confusion and incommensurability among those concerned with health care improvement. Participants in the quality improvement (QI) space typically stress their own, often narrow, perspective, failing to place QI in context or to acknowledge other approaches. In order to improve delivery of health care, the following is required:

Provide a unifying framework for improving health care. We argue this is best done under a Health System Science (HSS) framework but with full understanding that the fundamental principles of HSS are rooted in evidence‐based medicine (EBM) and decision sciences.

Understand that QI initiatives are fundamentally local activities. Hence, incentivizing bottom‐up, local QI initiatives would improve health care delivery to a far greater extent than the current top‐down initiatives undertaken in a response to various regulatory mandates.

Akin to the “Choosing Wisely” initiative, which challenged professional societies, each institution should identify (a) the extent to which its practices are evidence‐based and (b) the top 5 health care practices or interventions that, at a given institution, represent overuse, underuse, or misuse/error or undermine clinicians' efforts to deliver kind and empathic care.

Providing a framework that can unify the current patchwork of the initiatives would help create a common basis to help align all the existing QI efforts. In addition, thinking small (at local level) may lead to health care quality improvements that national initiatives (thinking big), focused on regulation, competition, or legal requirements, have failed to achieve.
Development of a multiplex real‐time PCR for simultaneous detection of Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus in food samples
Authors: Wei Shuai , Daliri Eric Banan‐Mwine , Chelliah Ramachandran , Park Byung‐Jae , Lim Ji‐Su , Baek Myo‐Ah , Nam Yong‐Suk , Seo Kun‐Ho , Jin Yong‐Guo , Oh Deog‐Hwan
Published: November 2018

Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus caused problems in public health and food safety. A multiplex real‐time PCR (qPCR) for simultaneous detection of these three pathogens in different kinds of food was developed. A high specificity (100%) was obtained using 21 target strains and 19 nontarget strains. Standard curves for pure cultures covered seven orders of magnitude (from 108 to 102 cfu/ml) with high amplification efficiencies ranging from 94.2 to 105.4% with R‐squares over 0.999. When multiplex qPCR was applied for artificially contaminated cherry tomato, milk, and spam samples, a detection limit of 103 cfu/g or ml was obtained for these three bacteria. When low levels (0.4–5.5 cfu/25 g or ml) of bacteria were inoculated in three kinds of food samples and cultured in tryptic soy broth for 24 hr, results obtained from multiplex real‐time and conventional culture methods were not significantly different for all three food matrices based on Mantel–Haenszel chi‐square test. Only for B. cereus in milk, positive portions detected by qPCR were significantly higher than those detected by culture method. Hence, the multiplex qPCR developed in this study is highly specific and effective for simultaneous detection B. cereus, L. monocytogenes, and S. aureus in food samples.

Practical applications

Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus are three major foodborne pathogens and have been found in a wide range of foods. We developed a multiplex qPCR specific targeting groEL, iap, and nuc genes with a high amplification efficiency. Different food samples (cherry tomato, milk, and spam) were tested for evaluating the performance of the multiplex qPCR. The detection results by qPCR were compared with the conventional culture methods and no significant differences were found using Mantel–Haenszel chi‐square test. This study provides the information of the developed multiplex qPCR for detecting three specific foodborne pathogens and applications in food samples, which will be helpful for further studies about simultaneous detection of several targets in food samples using multiplex PCR.
Local Employment Conditions and Unintended Pregnancy
Authors: Su Jessica Houston
Published: November 2018

Objective

This study examined the relationship between local employment conditions and unintended pregnancy.

Background

Economic conditions shape the decisions that Americans make about their families, such as whether and when to have children. Women have fewer children during economic downturns, but it is unclear how the economy is related to another dimension of fertility: unintended pregnancy. This is an important avenue of research because unintended pregnancy is related to population health and social inequality.

Method

This study analyzed a unique restricted data set that combined data from a nationally representative sample of women aged 20 to 44 years from the National Survey of Family Growth (2002, 2006–2010, and 2011–2013), with employment data from the U.S. Census and the American Community Survey (n = 13,702). It employed multinomial logistic regressions to estimate the odds that respondents had an unintended pregnancy as a function of local employment conditions in their Core Based Statistical Area.

Results

Higher unemployment rates were associated with lower odds of unintended pregnancy overall (including both mistimed and unwanted) relative to no pregnancy, adjusting for observable and unobservable characteristics. Women were less likely to have unwanted pregnancies in particular. This relationship was evident among women with both high and low levels of education, although those with the lowest education had the steepest declines.

Conclusion

Local employment conditions are an important context for fertility and are related to women's pregnancy intentions.
Methadone maintenance treatment as social control: Analyzing patient experiences
Authors: O'Byrne Patrick , Jeske Pearson Courtney
Published: November 2018

Methadone maintenance treatment (MMT) is a harm reduction approach for persons who wish to stop using opioids and is rather effective if used for a minimum of 12 months. Notably, research demonstrates that many persons enrolled in MMT programs discontinue care before this time, limiting its effects. To better understand this process, we undertook an exploratory descriptive qualitative study and interviewed 12 men and women who were using MMT. Using the theoretical work of Foucault and Hardt and Negri, the interview data highlighted that MMT continues to be strongly stigmatized, and that it is a system of care that involves rewards and penalties, based on if patients behave according to prescribed norms. These results suggest that MMT is a disciplinary mechanism, albeit one that impedes its own access. We consequently recommend that healthcare providers work to facilitate access to MMT, which means altering care delivery.
Visible light accelerates the ultraviolet A‐induced degradation of eumelanin and pheomelanin
Authors: Ito Shosuke , Kolbe Ludger , Weets Gudrun , Wakamatsu Kazumasa
Published: November 2018

Exposure to excess ultraviolet (UV) A radiation induces the degradation/modification of both eumelanin and pheomelanin that may be deleterious to pigmented tissues. Although the spectral distribution of solar energy comprises nearly half of visible light (VL), few studies have been conducted to examine the role of VL in the photodegradation of both types of melanin, either VL alone or in combination with UVA. In this study, we examined the effects of physiological doses of VL (150 to 300 J cm−2) alone or in combination with a physiological dose of UVA (20 J cm−2) in normal human epidermal melanocytes. The degradation/modification of melanin structures was evaluated by our chemical degradation—high performance liquid chromatography methods. The results show that VL accelerates UVA‐induced changes in the structural features of both eumelanin and pheomelanin, although VL or UVA alone induced only minor changes in melanin structure. The differential spectral method provides support for the additive effects of VL.
Interdisciplinary Research as an Iterative Process to Build Disaster Systems Knowledge
Authors: Subedi Jishnu , Houston J. Brian , Sherman‐Morris Kathleen
Published: November 2018

Disasters occur at the intersections of social, natural, and built environments, and robust understanding of these interactions can only occur through insight generated from different disciplines. Yet, there are cultural, epistemological, and methodological differences across the many disciplines concerned with hazards and disasters that can make conducting interdisciplinary research difficult. Approaches are needed to overcome these challenges. This article argues that interdisciplinary disaster research can be successful when it entails an iterative process in which researchers from different disciplines work collaboratively and exert reciprocal influence to generate disaster systems knowledge. Disaster systems knowledge is interdisciplinary and is defined as a comprehensive understanding of the intersections of built, natural, and human environmental factors and their interplay in hazards and disasters. The iterative process can reduce disciplinary biases and privileges by encouraging collaboration among researchers to help ensure disciplinary knowledge complements other disciplinary knowledge, to ultimately generate interdisciplinary disaster systems knowledge. The article concludes by illustrating the process by analyzing a research case study of an interdisciplinary approach to volcanic risk reduction.
Current Changes in the Location of Industry in the Suburban Zone of A Post‐Socialist City. Case Study of Wrocław (Poland)
Authors: Brezdeń Paweł , Szmytkie Robert
Published: November 2018

In the time of post‐industrialism, the increasing costs of life, scientific and technical development, an increase in the level of education and ecological barriers resulted in the decentralization of economic activity. One of the consequences of this is an increase in the locational attractiveness of the suburban zone. The aim of the paper is to evaluate the contemporary processes concerning location and concentration of industry in a post‐socialist city illustrated with an example of the city of Wrocław. The conducted research enabled us to determine the functional specialisation of gminas (municipalities), which served as the basis for the construction of a simplified model of the suburban zone in the post‐industrial period. In order to diagnose the extent of development and the level of spatial differentiation of the process of industrial activity concentration, the authors applied a location quotient (LQ) as well as a taxonomic method of linear ordering of distances from so‐called development pattern.
What “Moves” the Populations Most Likely to Be Physically Inactive—Women and Older Adults? Evidence From Mueller, a Mixed-Use Neighborhood in Austin, Texas
Authors: Calise Tamara Vehige , DeJong William , Heren Timothy , Wingerter Chloe , Kohl Harold W.
Published: November 2018

Background: Older age groups are less likely than their younger counterparts to be regularly active and women are even less active. Ecological models suggest that multiple levels of influence with each level influencing the next level impacts physical activity behaviors. Methods: Hierarchical multiple regressions were used to determine factors within and across the ecological model that predicted both total physical activity and walking for recreation. Findings: The overall predictors of total physical activity were different than those of walking for recreation, with the exception of dog ownership and perceived barriers. Gender and age were significant predictors of walking for recreation, but these associations were not present for total physical activity. Women and older adults walked more for recreation in a mixed-use community, Mueller, (and thus engaged in more total physical activity) compared with men and younger adults. Conclusion: Behavior-specific physical activity as well as total physical activity led to a better understanding of factors that may impact behavior among an overall aging population, especially women. This level of specificity is important in understanding specific factors that are associated with physical activity among vulnerable populations and can help guide the development of tailored, cost-effective, and efficient policies and interventions.
Television Watching as Sedentary Behavior and Atrial Fibrillation: The Atherosclerosis Risk in Communities Study
Authors: Kubota Yasuhiko , Alonso Alvaro , Shah Amil M. , Chen Lin Y. , Folsom Aaron R.
Published: November 2018

Background: There is no research on the association of television (TV) watching with atrial fibrillation (AF). Methods: From 1987 to 1989, the authors obtained information on the frequency of TV watching in 14,458 participants, aged 45–64 years, without a history of AF. The authors used the Cox proportional hazards model to estimate hazard ratios and their 95% confidence intervals of AF according to the frequency of TV watching (“never or seldom,” “sometimes,” “often,” or “very often”). Results: During the 294,553 person-years of follow-up, the authors identified 2,476 AF events. Adjustment for other potential confounding factors, including physical activity, did not change the associations, in which “very often” watching TV carried 1.28 (95% confidence interval, 1.09–1.50) times AF risk compared with “never or seldom” watching TV (P for trend = .002). Even among individuals who met a recommended level of physical activity, watching TV “very often” carried 1.36 (1.02–1.82) times AF risk, compared with watching TV “never or seldom.” Conclusion: Greater frequency of TV watching was independently associated with increased risk of AF even after adjusting for physical activity. Moreover, a recommended level of physical activity did not eliminate the increased risk of frequent TV watching for AF. Avoiding frequent TV watching might be beneficial for AF prevention.
The paradox of mutations and cancer
Authors: Chanock Stephen J.
Published: November 2018

Esophageal tissue often contains driver mutations in people without cancer
10,368 first dates: Microfluidic T cell matchmaking
Authors: Au Sam H.
Published: November 2018

Coencapsulation of T cells and target cells into arrays of subnanoliter droplets improves the identification of functional T cell receptors.
Noncanonical DNA modification revealed in glioblastoma
Authors: Zhang Qing
Published: November 2018

ALKBH1 promotes glioblastoma by controlling the
N
6
-methyladenine DNA modification on hypoxia response genes.
Field Performance and Diagnostic Accuracy of a Low-Cost Instrument-Free Point-of-Care CD4 Test (Visitect CD4) Performed by Different Health Worker Cadres among Pregnant Women
Authors: Luchters Stanley , Technau Karl , Mohamed Yasmin , Chersich Matthew F. , Agius Paul A. , Pham Minh D. , Garcia Mary L. , Forbes James , Shepherd Andrew , Coovadia Ashraf , Crowe Suzanne M. , Anderson David A.
Published: November 2018

Measuring CD4 counts remains an important component of HIV care. The Visitect CD4 is the first instrument-free low-cost point-of-care CD4 test with results interpreted visually after 40 min, providing a result of ≥350 CD4 cells/mm
3
.
Capture of a Hyena-Specific Retroviral Envelope Gene with Placental Expression Associated in Evolution with the Unique Emergence among Carnivorans of Hemochorial Placentation in Hyaenidae
Authors: Funk Mathis , Cornelis Guillaume , Vernochet Cécile , Heidmann Odile , Dupressoir Anne , Conley Alan , Glickman Stephen , Heidmann Thierry
Published: November 2018

The placenta is the most diverse organ among mammals, due in part to stochastic capture of retroviral envelope genes. In carnivorans, capture of
syncytin-Car1
took place 80 Mya. It is fusogenic, expressed at the syncytialized placental maternofetal interface, and conserved among all carnivorans, consistent with their shared endotheliochorial placenta. Hyenas are a remarkable exception, with a highly invasive hemochorial placenta, as found in humans, where disruption of maternal blood vessels results in maternal blood bathing the syncytial maternofetal interface. In this study, we identified a retroviral envelope gene capture and exaptation that took place about 30 Mya and is coincident with the emergence of the Hyaenidae, being conserved in all extant hyena species. It is expressed at the maternofetal interface in addition to the shared
syncytin-Car1
gene. This new
env
gene, not present in any other carnivoran, is a likely candidate to be responsible for the specific structure of the hyena placenta.
Clear lens extraction for the management of primary angle closure glaucoma: surgical technique and refractive outcomes in the EAGLE cohort
Authors: Day Alexander C , Cooper David , Burr Jennifer , Foster Paul J , Friedman David S , Gazzard Gus , Che-Hamzah Jemaima , Aung Tin , Ramsay Craig R , Azuara-Blanco Augusto
Published: November 2018

Background

To describe the surgical technique and refractive outcomes following clear lens extraction (CLE) in the Effectiveness, in Angle-closure Glaucoma, of Lens Extraction trial.

Methods

Review of prospectively collected data from a multicentre, randomised controlled trial comparing CLE and laser peripheral iridotomy. Eligible participants were ≥50 years old and newly diagnosed with (1) primary angle closure (PAC) with intraocular pressure above 30 mm Hg or (2) PAC glaucoma. We report the postoperative corrected distance visual acuity (CDVA) and refractive outcomes at 12 and 36 months postoperatively for those who underwent CLE.

Results

Of the 419 participants, 208 were randomised to CLE. Mean baseline CDVA was 77.9 (SD 12.4) letters and did not change significantly at 36 months when mean CDVA was 79.9 (SD 10.9) letters. Mean preoperative spherical equivalents were +1.7 (SD 2.3) and +0.08 (SD 0.95) diopters (D) at 36 months. Fifty-nine per cent and 85% eyes were within ±0.5D and ±1.0D of predicted refraction, respectively, at 36 months.

Conclusions

Mean CDVA in patients undergoing CLE for angle-closure glaucoma appeared stable over the 3-year study period. Refractive error was significantly reduced with surgery but refractive predictability was suboptimal.

Trial registration number
Optical coherence tomography angiography in exudative age-related macular degeneration: a predictive model for treatment decisions
Authors: Coscas Florence , Lupidi Marco , Boulet Jean François , Sellam Alexandre , Cabral Diogo , Serra Rita , Français Catherine , Souied Eric H , Coscas Gabriel
Published: November 2018

Aims

To evaluate on optical coherence tomography angiography (OCT-A), the predictive role of different qualitative findings of choroidal neovascularisations (CNV) in assessing the status of exudative age-related macular degeneration (eAMD) and to develop a potential model to predict the CNV activity.

Methods

Retrospective review of the multimodal imaging records of patients with eAMD obtained during treatment for type 1 or type 2 CNV. The qualitative analysis of CNVs on OCT angiograms assessed the presence or absence of tiny branching vessels, loops, peripheral anastomotic arcades and choriocapillaris hypointense halo. These findings were then correlated with those of structural OCT scans. A score forecast was built and validated.

Results

One hundred and twenty-six eAMD eyes were enrolled in the study. Exudation was observed in 90 eyes (71%) on structural OCT. The qualitative OCT-A analysis revealed: tiny branching vessels in 82.5% of the cases, vascular loops in 81.7%, peripheral anastomotic arcades in 66.7% and choriocapillaris hypointense halo in 54.8%. In the univariate analysis, each OCT-A parameter showed a statistically significant correlation with exudation on structural OCT (p<0.001). The overall analysis demonstrated a sensitivity of 96.7% and a positive predictive value of 87.9%. In the multivariate analysis, a model with four criteria predicted an exudative lesion in 97.6% of cases and one with two criteria (tiny branching vessels and peripheral anastomotic arcades) in 71.2%.

Conclusions

The presence of tiny branching vessels and a peripheral anastomotic arcade appears to predict the lesion activity with a good accuracy and the model based on four criteria enables optimal decisions regarding retreatment in eAMD.
Real-world persistence and adherence to oral antimuscarinics and mirabegron in patients with overactive bladder (OAB): a systematic literature review
Authors: Yeowell Gillian , Smith Philip , Nazir Jameel , Hakimi Zalmai , Siddiqui Emad , Fatoye Francis
Published: November 2018

Purpose

To evaluate persistence and adherence of oral pharmacotherapy used in the treatment of overactive bladder (OAB) in a real-world setting.

Materials and methods

Systematic literature searches of six electronic publication databases were performed to identify observational studies of patients with OAB treated with antimuscarinics and/or mirabegron. Studies obtaining persistence and adherence data from sources other than electronic prescription claims were excluded. Reference lists of identified studies and relevant systematic reviews were assessed to identify additional relevant studies.

Results

The search identified 3897 studies, of which 30 were included. Overall, persistence ranged from 5% to 47%. In studies reporting data for antimuscarinics and mirabegron (n=3), 1-year persistence was 12%–25% and 32%–38%, respectively. Median time to discontinuation was <5 months for antimuscarinics (except one study (6.5 months)) and 5.6–7.4 months for mirabegron. The proportion of patients adherent at 1 year varied between 15% and 44%. In studies reporting adherence for antimuscarinics and mirabegron, adherence was higher with mirabegron (mean medication possession ratio (MPR): 0.59 vs 0.41–0.53; mean proportion of days covered: 0.66 vs 0.55; and median MPR: 0.65 vs 0.19–0.49). Reported determinants of persistence and adherence included female (sex), older age group, use of extended-release formulation and treatment experience.

Conclusion

Most patients with OAB discontinued oral OAB pharmacotherapy and were non-adherent 1 year after treatment initiation. In general, mirabegron was associated with greater persistence and adherence compared with antimuscarinics. Combined with existing clinical trial evidence, this real-world review merits consideration of mirabegron for first-line pharmacological treatment among patients with OAB.

PROSPERO registration number

CRD42017059894.
Baseline clinical characteristics, comorbidities and prescribed medication in a real-world population of patients with idiopathic pulmonary fibrosis: the PROOF registry
Authors: Wuyts Wim A , Dahlqvist Caroline , Slabbynck Hans , Schlesser Marc , Gusbin Natacha , Compere Christophe , Maddens Sofie , Kirchgaessler Klaus-Uwe , Bartley Karen , Bondue Benjamin
Published: November 2018

Introduction

PROOF (a Prospective Observational Registry to Describe the Disease Course and Outcomes of Idiopathic Pulmonary Fibrosis) is an ongoing, observational registry initiated in 2013 with the aim of collecting real-world data from patients with idiopathic pulmonary fibrosis (IPF). Here, we present comprehensive baseline data, which were collected from patients on registry inclusion.

Methods 

Patients with IPF were enrolled across eight centres in Belgium and Luxembourg. Baseline data collected included demographics, diagnostic information and clinical characteristics, including lung function and health-related quality of life. Data on comorbidities and prescribed medication were also collected.

Results 

A total of 277 patients were enrolled in the PROOF registry. At inclusion, 92.8% and 6.5% of patients had a definite or probable diagnosis of IPF, respectively. Mean per cent predicted forced vital capacity and carbon monoxide diffusing capacity were 80.6% and 46.9%, respectively. Mean St. George’s Respiratory Questionnaire total score was 47.0, and mean Cough-Visual Analogue Scale score was 30.5 mm. The most prevalent comorbidities reported at inclusion were gastrointestinal disorders (50.2%), including gastro-oesophageal reflux disease (47.3%) and metabolism and nutrition disorders (39.7%). At inclusion, 67.2% and 2.2% of patients were prescribed pirfenidone and nintedanib, respectively, with treatment initiated either prior to, or at the time of, inclusion. Medication prescribed concomitantly with pirfenidone included antihypertensives (54.8%), statins (37.1%) and prophylactic antithrombotics/anticoagulants (36.6%).

Conclusion

The PROOF registry provides valuable demographic and clinical data from a real-world population of patients with IPF in Belgium and Luxembourg, demonstrating the high burden of comorbidities and prescribed medication in these patients. Longitudinal data from this patient population will be investigated in future analyses.

Trial registration

PROOF is registered with the relevant authorities in Belgium and Luxembourg, with registration to Comité National d’Éthique et de Recherché (CNER) N201309/03 – 12 September 2013 and a notification to Comité National de Protection des Données (CNDP).
Circulating tumour DNA, microRNA and metabolites in cerebrospinal fluid as biomarkers for central nervous system malignancies
Authors: Zorofchian Soheil , Iqbal Fatima , Rao Mayank , Aung Phyu P , Esquenazi Yoshua , Ballester Leomar Y
Published: November 2018

Central nervous system (CNS) malignancies can be difficult to diagnose and many do not respond satisfactorily to existing therapies. Monitoring patients with CNS malignancies for treatment response and tumour recurrence can be challenging because of the difficulty and risks of brain biopsies, and the low specificity and sensitivity of the less invasive methodologies that are currently available. Uncertainty about tumour diagnosis or whether a tumour has responded to treatment or has recurred can cause delays in therapeutic decisions that can impact patient outcome. Therefore, there is an urgent need to develop and validate reliable and minimally invasive biomarkers for CNS tumours that can be used alone or in combination with current clinical practices. Blood-based biomarkers can be informative in the diagnosis and monitoring of various types of cancer. However, blood-based biomarkers have proven suboptimal for analysis of CNS tumours. In contrast, circulating biomarkers in cerebrospinal fluid (CSF), including circulating tumour DNA, microRNAs and metabolites, hold promise for accurate and minimally invasive assessment of CNS tumours. This review summarises the current understanding of these three types of CSF biomarkers and their potential use in neuro-oncologic clinical practice.
Structural network disruption markers explain disability in multiple sclerosis
Authors: Charalambous Thalis , Tur Carmen , Prados Ferran , Kanber Baris , Chard Declan T , Ourselin Sebastian , Clayden Jonathan D , A M Gandini Wheeler-Kingshott Claudia , Thompson Alan J , Toosy Ahmed T
Published: November 2018

Objective

To evaluate whether structural brain network metrics correlate better with clinical impairment and information processing speed in multiple sclerosis (MS) beyond atrophy measures and white matter lesions.

Methods

This cross-sectional study included 51 healthy controls and 122 patients comprising 58 relapsing–remitting, 28 primary progressive and 36 secondary progressive. Structural brain networks were reconstructed from diffusion-weighted MRIs and standard metrics reflecting network density, efficiency and clustering coefficient were derived and compared between subjects’ groups. Stepwise linear regression analyses were used to investigate the contribution of network measures that explain clinical disability (Expanded Disability Status Scale (EDSS)) and information processing speed (Symbol Digit Modalities Test (SDMT)) compared with conventional MRI metrics alone and to determine the best statistical model that explains better EDSS and SDMT.

Results

Compared with controls, network efficiency and clustering coefficient were reduced in MS while these measures were also reduced in secondary progressive relative to relapsing–remitting patients. Structural network metrics increase the variance explained by the statistical models for clinical and information processing dysfunction. The best model for EDSS showed that reduced network density and global efficiency and increased age were associated with increased clinical disability. The best model for SDMT showed that lower deep grey matter volume, reduced efficiency and male gender were associated with worse information processing speed.

Conclusions

Structural topological changes exist between subjects’ groups. Network density and global efficiency explained disability above non-network measures, highlighting that network metrics can provide clinically relevant information about MS pathology.
Neurochemical correlates of functional decline in amyotrophic lateral sclerosis
Authors: Cheong Ian , Deelchand Dinesh K , Eberly Lynn E , Marjańska Małgorzata , Manousakis Georgios , Guliani Gaurav , Walk David , Öz Gülin
Published: November 2018

Objective

To determine whether proton magnetic resonance spectroscopy (1H-MRS) can detect neurochemical changes in amyotrophic lateral sclerosis (ALS) associated with heterogeneous functional decline.

Methods

Nineteen participants with early-stage ALS and 18 age-matched and sex ratio-matched controls underwent ultra-high field1H-MRS scans of the upper limb motor cortex and pons, ALS Functional Rating Scale-Revised (ALSFRS-R total, upper limb and bulbar) and upper motor neuron burden assessments in a longitudinal observational study design with follow-up assessments at 6 and 12 months. Slopes of neurochemical levels over time were compared between patient subgroups classified by the rate of upper limb or bulbar functional decline.1H-MRS and clinical ratings at baseline were assessed for ability to predict study withdrawal due to disease progression.

Results

Motor cortex totalN-acetylaspartate tomyo-inositol ratio (tNAA:mIns) significantly declined in patients who worsened in upper limb function over the follow-up period (n=9, p=0.002). Pons glutamate + glutamine significantly increased in patients who worsened in bulbar function (n=6, p<0.0001). Neurochemical levels did not change in patients with stable function (n=5–6) or in healthy controls (n=14–16) over time. Motor cortex tNAA:mIns and ALSFRS-R at baseline were significantly lower in patients who withdrew from follow-up due to disease progression (n=6) compared with patients who completed the 12-month scan (n=10) (p<0.001 for tNAA:mIns; p<0.01 for ALSFRS-R), with a substantially larger overlap in ALSFRS-R between groups.

Conclusion

Neurochemical changes in motor areas of the brain are associated with functional decline in corresponding body regions.1H-MRS was a better predictor of study withdrawal due to ALS progression than ALSFRS-R.
Antibodies toChlamydia trachomatisand reproductive health issues in women with SLE: a case–control study
Authors: Santos Alba , Greub Gilbert , Aeby Sébastien , Wunder Dorothea , Pantaleo Giuseppe , Ribi Camillo
Published: November 2018

Background

SLE is an autoimmune condition affecting predominantly women. Little is known regardingChlamydia trachomatisinfection in women with SLE, which may drive autoimmunity and contribute to obstetrical and vascular complications.

Methods

This single-centre, case–control study set primary endpoint in the comparative seropositivity rate toC. trachomatismajor outer membrane protein (MOMP) and chlamydial heat-shock protein-60 (cHSP60) in age-matched subjects. The secondary endpoints were obstetrical outcomes, cardiovascular events and results from screening procedures for cervical cancer.

Results

Eighty-four women with SLE and 50 age-matched controls were included. Seropositivity toC. trachomatisdid not differ significantly between groups (10% of cases positive for anti-MOMP vs 12% of controls; 43% of cases positive for anti-cHSP60 vs 32% of controls). Women with SLE were more often of non-Caucasian ethnicity and had lower educational level. They relied less frequently on oral contraception and resorted more frequently to elective pregnancy termination. Pre-eclampsia and ectopic pregnancy occurred only in SLE. Women with SLE also experienced more cardiovascular events. In SLE, antibodies to cHSP60 were associated with a history of pericarditis and abnormal screening tests for cervical cancer. Antibody titres toC. trachomatiswere not associated with disease activity or SLE treatment, nor were there associations with other gynaecological, obstetrical or vascular outcomes.

Conclusion

Prevalence of antibodies toC. trachomatiswas not increased in women with SLE. No significant association was found between these antibodies and obstetrical or cardiovascular complications.
Drawing the line on physician-assisted death
Authors: Jansen Lynn A , Wall Steven , Miller Franklin G
Published: November 2018

Drawing the line on physician assistance in physician-assisted death (PAD) continues to be a contentious issue in many legal jurisdictions across the USA, Canada and Europe. PAD is a medical practice that occurs when physicians either prescribe or administer lethal medication to their patients. As more legal jurisdictions establish PAD for at least some class of patients, the question of the proper scope of this practice has become pressing. This paper presents an argument for restricting PAD to the terminally ill that can be accepted by defenders as well as critics of PAD for the terminally ill. The argument appeals to fairness-based paternalism and the social meaning of medical practice. These two considerations interact in various ways, as the paper explains. The right way to think about the social meaning of medical practice bears on fair paternalism as it relates to PAD and vice versa. The paper contends that these considerations have substantial force when directed against proposals to extend PAD to non-terminally ill patients, but considerably less force when directed against PAD for the terminally ill. The paper pays special attention to the case of non-terminally ill patients who suffer from treatment-resistant depression, as these patients present a potentially strong case for extending PAD beyond the terminally ill.
Computer knows best? The need for value-flexibility in medical AI
Authors: McDougall Rosalind J
Published: November 2018

Artificial intelligence (AI) is increasingly being developed for use in medicine, including for diagnosis and in treatment decision making. The use of AI in medical treatment raises many ethical issues that are yet to be explored in depth by bioethicists. In this paper, I focus specifically on the relationship between the ethical ideal of shared decision making and AI systems that generate treatment recommendations, using the example of IBM’s Watson for Oncology. I argue that use of this type of system creates both important risks and significant opportunities for promoting shared decision making. If value judgements are fixed and covert in AI systems, then we risk a shift back to more paternalistic medical care. However, if designed and used in an ethically informed way, AI could offer a potentially powerful way of supporting shared decision making. It could be used to incorporate explicit value reflection, promoting patient autonomy. In the context of medical treatment, we need value-flexible AI that can both respond to the values and treatment goals of individual patients and support clinicians to engage in shared decision making.
Analyses of clinical outcomes after severe pelvic fractures: an international study
Authors: Jung Kyoungwon , Matsumoto Shokei , Smith Alan , Hwang Kyungjin , Lee John Cook-Jong , Coimbra Raul
Published: November 2018

Background

This study aimed to compare treatment outcomes between patients with severe pelvic fractures treated at a representative trauma center that was established in Korea since 2015 and matched cases treated in the USA.

Methods

Two cohorts were selected from a single institution trauma database in South Korea (Ajou Trauma Data Bank (ATDB)) and the National Trauma Data Bank (NTDB) in the USA. Adult blunt trauma patients with a pelvic Abbreviated Injury Scale >3 were included. Patients were matched based on covariates that affect mortality rate using a 1:1 propensity score matching (PSM) approach. We compared differences in outcomes between the two groups, performed survival analysis for the cohort after PSM and identified factors associated with mortality. Lastly, we analyzed factors related to outcomes in the ATDB dataset comparing a period prior to the implementation of the trauma center according to US standards, an interim period and a postimplementation period.

Results

After PSM, a total of 320 patients (160 in each cohort) were identified for comparison. Inhospital mortality was significantly higher in the ATDB cohort using χ2test, but it was not statistically significant when using Kaplan-Meier survival curves and Cox regression analysis. Moreover, the mortality rate was similar comparing the NTDB cohort to ATDB data reflecting the post-trauma center establishment period. Older age, lower systolic blood pressure (SBP) and Glasgow Coma Scale (GCS) at admission were factors associated with mortality.

Discussion

Mortality rate after severe pelvic fractures was significantly associated with older age, lower SBP and GCS scores at admission. Efforts to establish a trauma center in South Korea led to improvement in outcomes, which are comparable to those in US centers.

Level of evidence

Level IV.
Intra-annual variability in isotopic and total nitrogen in tree rings of old growth Sitka spruce from coastal British Columbia
Authors: Reimchen T.E. , Arbellay Estelle
Published: November 2018

Tree-ring studies using increment cores have increasingly measured elemental (N) and isotopic (δ15N) nitrogen values to evaluate environmental changes in the nitrogen cycle. The paucity of nitrogen in wood has constrained tree-ring analyses to annual resolution. Based on 77 rings and 310 sub-rings, we provide evidence for substantial intra-annual variability in N and δ15N values in the heartwood of 11 geographically widely separated, old growth Sitka spruce [Picea sitchensis (Bong.) Carrière] trees from coastal British Columbia. The range of N and δ15N values within rings (intra-annual level) was on average equal to or up to seven-times the range among rings (inter-annual level). Most rings showed a seasonal reduction in N values from early to late growth and a corresponding increase to the early growth of the following season (P < 0.05 to 0.001, Mann–Whitney–Wilcoxon test). By contrast, intra-annual changes in δ15N values were highly variable among years and among trees, ranging from pronounced oscillations (4.0‰) to reasonable consistency. Our results allude to the potential importance of such intra-ring data for interpreting seasonal trends in nitrogen use and increasing understanding of ecological processes in the marine–terrestrial interface.