bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of phototesting in the diagnosis of photodermatoses: Retrospective study of 100 cases
Authors: Pralong Pauline , Ciszynski Meryl , Moncourier Marie , Beani Jean‐Claude , Charles Julie , Leccia Marie‐Therese
Published: July 2021

Background

Photodermatoses are sun‐related inflammatory skin diseases. They usually require phototesting in diagnosis. However, fewer and fewer medical centers in France are equipped with photobiological equipment.

Objectives

The main purpose was to evaluate the relevance of phototesting in photodermatosis diagnosis. The second goal was to study the proportions of the different kinds of photodermatosis found in this particular study.

Methods

This study was descriptive, retrospective, and mono‐centric. It was based on 100 consecutive patients, who have been phototested in a French University Hospital from 2014 to 2018. Phototesting included determination of the minimal erythematous dose (MED), UVA and UVB phototests, and photopatch testing.

Results

The use of phototesting led to 60% of photodermatosis diagnosis and formally eliminated the latter in 13% of the cases. The diagnosis remained undetermined in 27% of the cases.

Nineteen cases of polymorphous light eruption (PLE), 14 cases of photocontact dermatitis (PCD), 10 cases of solar urticaria, 8 cases of photo‐aggravated atopic eczema, 5 cases of chronic actinic dermatitis, and 2 cases of systemic photosensitization were diagnosed. The allergens involved in PCD were topical non‐steroidal anti‐inflammatory drug (NSAID) in 9 cases, sunscreens in 3 cases, and fragrance in 2 cases. The average amount of time between the first symptoms and actual phototesting was about 7,5 years.

Conclusion

This study confirms phototesting is truly useful. PLE was the most common form of photodermatosis, followed by PCD and solar urticaria. As photodermatosis could imply severe diseases sometimes requiring hospitalization, it is critical to maintain this expertise.
Effect of prenatal screening on trends in perinatal mortality associated with congenital anomalies before and after the introduction of prenatal screening: A population‐based study in the Northern Netherlands
Authors: Bardi Francesca , Bergman Jorieke E. H. , Bouman Katelijne , Erwich Jan Jaap , Duin Leonie K. , Walle Hermien E. K. , Bakker Marian K.
Published: July 2021

Background

Perinatal mortality in foetuses/children with congenital anomalies remains high. Prenatal diagnosis, essential for risk assessment and organisation of perinatal/postnatal care, offers parents the opportunity to consider the termination of pregnancy. In times of quick changes in prenatal screening programmes, it is relevant to evaluate the effect of prenatal screening on perinatal mortality rates.

Objectives

The objective of this study was to study trends in early foetal and perinatal mortality associated with congenital anomalies before/after the introduction of the Dutch prenatal screening programme.

Methods

This population‐based cohort study included 8535 foetuses/neonates with congenital anomalies born in the Northern Netherlands between 2001 and 2017. Total deaths were defined as sum of early foetal (before 24 weeks’ gestation) and perinatal deaths (from 24 weeks’ gestation till day 7 post‐partum). Foetal deaths were categorised into spontaneous or elective termination of pregnancy for foetal anomalies (TOPFA). Trends in total mortality as well as early foetal and perinatal mortality were studied. Joinpoint regression was used to calculate the average annual percentage chance (AAPC) and identify linear trends in mortality within subperiods.

Results

Total and perinatal mortality were 17% and 4%. Total mortality was higher in abnormal karyotype and central nervous system anomalies. We observed an increase in total mortality over time: 11.9% in 2001 versus 21.9% in 2017 (AAPC 2.6, 95% confidence interval [CI] 1.5, 3.7), caused by an increase in early foetal mortality from 5.5% to 19.2% (AAPC 8.7, 95% CI 4.7, 12.9) and a decrease in perinatal mortality from 6.4% to 2.7% (AAPC −5.6, 95% CI −10.0, −1.0). The increase in early foetal mortality reflects an increase in TOPFA from 3.6% to 16.9% (AAPC 8.3, 95% CI 4.2, 12.7), mostly occurring at 13–14 and 20–23 weeks’ gestation.

Conclusions

The introduction of the prenatal screening programme led to a decrease in perinatal mortality among foetuses and neonates with congenital anomalies and a marked increase in early foetal mortality before 24 weeks’ gestation due to higher rates of TOPFA.
Settlement yields in large‐scale in situ culture of Caribbean coral larvae for restoration
Authors: Miller Margaret W. , Latijnhouwers Kelly R. W. , Bickel Aric , Mendoza‐Quiroz Sandra , Schick Mark , Burton Keoki , Banaszak Anastazia T.
Published: July 2021

The dire state of coral reefs demands a rapid increase in the scale and efficiency of coral restoration methods in addition to mitigating local and global stressors. Larval propagation can provide vast numbers of coral propagules from an individual spawning event and increased genetic diversity in restored populations. The conversion of embryos collected from wild, broadcast‐spawning populations to settlers that can be outplanted to the reef is a key component of this production process. We present preliminary results on settlement yield (i.e. % embryos converted to settled polyps on outplantable substrates) following in situ mass culture in floating mesocosms (Coral Rearing In‐situ Basins, or CRIBs; 5.6 m3 volume, 5.4 m2 surface area) that can be implemented independent of land‐based facilities. Ten trials over 2 years were conducted in three locations using five Caribbean broadcast‐spawning species. Embryos were added at different stocking densities and settlement was scored 2–4 weeks after fertilization. Two trials failed, resulting in no effective settlement, but the remaining eight trials resulted in between 1% and 11% settlement yield (overall mean 5.3%) and 77–100% of substrates exposed to larvae acquired settlers (average production: 700 substrates trial−1). Parallel land‐based trials showed a similar range (<1–14%) and mean (3.6%) settlement yield over nine trials. These values are also similar to the previously published lab and field‐based trials using Pacific Acropora spp. Continued optimization of CRIB design and execution is expected to improve consistency, overall yield, and efficiency in the production of sexual propagules for restoration.
Creep deformation measurement of ex‐service 12% Cr steel over nonuniform stress fields using digital image correlation
Authors: van Rooyen Melody , Forsey Alexander N. , Gungor Salih , Becker Thorsten H.
Published: July 2021

Deterioration assessment of materials is essential to the continued effective operation of critical components in thermal power plants. Establishing the degree of creep exhaustion of power engineering alloys operating at high temperatures and stresses guides maintenance strategies to ensure reliable plant operation. Within progressive inspection philosophies, traditional laboratory‐based creep testing is often difficult to conduct on ex‐service steel due to the limited material availability from which to machine standard specimen geometries. This work investigates a technique for the measurement of creep strain curves at several stresses and at 600°C from a single test using a nontraditional specimen geometry together with full‐field strain measurement through digital image correlation (DIC). Of interest is ex‐service X20CrMoV12‐1 (X20) which is widely used in older, subcritical thermal power plants. The paper aims to show that multiple creep curves can be resolved over a spatially varying stress field using DIC whilst preserving material economy. Differences in creep behaviour between ex‐service X20 with varying levels of service exposure are evident from quantitative comparisons of the creep strain and rate curves through threshold stress computation which agrees with hardness measurements and microstructural observation of subgrains and precipitates using electron microscopy. These single‐specimen tests yield high densities of creep data which can be used in the calibration of creep damage models for characterisation of ex‐service X20.
A kinematic reconstruction of Iberia using intracontinental strike‐slip corridors
Authors: Frasca Gianluca , Manatschal Gianreto , Cadenas Patricia , Miró Jordi , Lescoutre Rodolphe
Published: July 2021

Despite considerable progress in restoring rifted margins, none of the current kinematic models can restore the Mesozoic motion of the Iberian block in full agreement with the circum‐Iberian geology. This conflict requires a revision of the kinematic description at the onset of divergence. The circum‐Iberian region has a unique geological dataset that allows calibration and testing of kinematic reconstructions and therefore it is an ideal candidate for testing intracontinental restoration approaches. Here we define intracontinental deforming regions, referred to as strike‐slip corridors, based on alignments of Mesozoic rift basins and/or transfer zones bordering rigid continental blocks. We use these strike‐slip corridors and data from the southern N‐Atlantic and Tethys to define the motion path of the Flemish Cap, Ebro and Iberia continental blocks. The resulting Mesozoic kinematic model for the Iberian block is compatible with recently published data and interpretations describing the Mesozoic circum‐Iberian geology. Large‐scale intracontinental strike‐slip corridors may offer a valid boundary condition for reconstructing continental block motion at the onset of divergence in intracontinental settings.
The spillover effect of trade policy along the value Chain: Evidence from China's rare earth‐related sectors
Authors: Chen Zhe , Hu Zhongzhong , Li Kai
Published: July 2021

This study examines the heterogeneous spillover effects of an export control policy from an upstream sector to its related downstream sectors. In 2010, China implemented tough policies on rare earth production and export that created a significant price premium for rare earth in foreign markets, thus offering downstream sectors in China cost advantages over their foreign competitors. This study exploits China's policy as an exogenous shock and performs a detailed examination of Chinese customs data. The results show that the export control policy has increased the export price of rare earth downstream products from China, whereas the effects on export quantity and value have been heterogeneous across sectors: they are significant for sectors in which the rare earth cost share is high, and the elasticity of substitution is low.
Development of a new thermal time model for describing tuber sprouting of Purple nutsedge (Cyperus rotundus L.)
Authors: Mijani Sajad , Rastgoo Mehdi , Ghanbari Ali , Nassiri Mahallati Mehdi , González‐Andújar José L.
Published: July 2021

Tubers are the main means of propagation in purple nutsedge (Cyperus rotundus L.), one of the most troublesome weeds competing in crop and pasture systems throughout the world. Tuber sprouting is highly linked to temperature, the main environmental factor limiting the growth of purple nutsedge. In the present study, a new thermal time model was developed for describing the temperature‐dependent tuber sprouting of purple nutsedge. This model was validated based on results from a laboratory tuber sprouting experiment performed under different temperature regimes. The proposed model is an integration of three equations comprising those of Gompertz, Dent like, and Segmented (GDS) functions, developed for describing cumulative sprouting, final sprouting and sprouting rate of purple nutsedge tubers respectively. The Gompertz‐based model fitted the data well (R2 = 0.94, RMSE %< 10). This model was also able to predict lag time (time up to start of sprouting), final sprouting and sprouting rate. A Weibull‐based model was only able to estimate temperature thresholds based on the final sprouting. Whereas, the GDS model predicted related temperature thresholds according to both final sprouting (optimal in the range of 20.31–29.72°C) and the absolute sprouting rate (optimum at 29.96°C). In conclusion, the proposed model is simple and includes parameters of a biological significance, simultaneously generating estimates of useful temperature thresholds and fitting cumulative tuber sprouting of purple nutsedge. Our study has also proved the superiority of the absolute sprouting rate index when calculating the temperature thresholds.
Development of a Harmonic Balance Method-Based Numerical Strategy for Blade-Tip/Casing Interactions: Application to NASA Rotor 37
Authors: Colaïtis Yann , Batailly Alain
Published: July 2021

In this study, a frequency-domain approach based on the harmonic balance method coupled to a predictor-corrector continuation algorithm is implemented for the qualitative analysis of blade-tip/casing contacts in aircraft engines. Unilateral contact and dry friction are taken into account through a regularized penalty law. To enhance the robustness of the methodology, particular attention is paid to the mitigation of the Gibbs phenomenon. To this end, the employed Alternating Frequency/Time scheme features a Lanczos σ-approximation so that spurious oscillations of the computed nonlinear contact forces become negligible. This approach is applied in combination with a model reduction technique on an industrial compressor blade: NASA rotor 37. In order to assess the influence of both the contact law regularization and the Lanczos σ-approximation, obtained results are thoroughly compared to an existing time integration-based numerical strategy relying on a Lagrange multiplier-based approach for contact treatment and that was previously confronted to experimental results. Presented results underline the very good agreement between the proposed methodology and the reference time integration numerical strategy. The proposed developments thus complement existing results on blade-tip/casing contact adding a much needed qualitative understanding of the interaction and an accurate assessment of the contact stiffening phenomenon.
Looping-in complexation and ion partitioning in nonstoichiometric polyelectrolyte mixtures
Authors: Friedowitz Sean , Lou Junzhe , Barker Kayla Patricia , Will Karis , Xia Yan , Qin Jian
Published: July 2021

The principles governing ion and macroion partitioning in nonstoichiometric coacervates are elucidated.
The major mechanism of melanoma mutations is based on deamination of cytosine in pyrimidine dimers as determined by circle damage sequencing
Authors: Jin Seung-Gi , Pettinga Dean , Johnson Jennifer , Li Peipei , Pfeifer Gerd P.
Published: July 2021

The sequence specificity of pyrimidine dimers with deaminated cytosines is highly similar to that of mutations in melanoma.
Increasing Engagement during Online Learning through the Use of Interactive Slides
Authors: Pakpour Nazzy , Souto Isabel , Schaffer Pamela
Published: July 2021

It is difficult in asynchronous online instruction to keep students engaged and motivated. The rapid and unexpected nature of the move to online instruction has meant that the content presented to students has been primarily static and linear.
Agar Art: a CURE for the Microbiology Laboratory
Authors: Adkins-Jablonsky Sarah J. , Arnold Erin , Rock Rachel , Gray Rosianna , Morris J. Jeffrey
Published: July 2021

We previously developed and assessed “The Art of Microbiology,” a course-based undergraduate research experience (CURE) which uses agar art to spur student experimentation, where we found student outcomes related to science persistence. However, these outcomes were not correlated with specific activities and gains were not reported from more than one class.
Test Corrections Appear To Benefit Lower-Achieving Students in an Introduction to Biology Major Course: Results of a Single-Site, One-Semester Study
Authors: Kemp Kyeorda
Published: July 2021

Student-performed assessment correction is a well-established practice in the field of teaching and learning. This practice engages students in the feedback process and promotes active learning, which may be particularly important when serving underrepresented minority students.
Laboratory Exercise to Measure Plasmid Copy Number by qPCR
Authors: David Benjamin , Li Jinbei , Masood Faisal , Blassick Caroline , Jensen Paul , Jensen Karin
Published: July 2021

Quantitative PCR (qPCR) has numerous applications in biology. In an education setting, qPCR provides students an opportunity to better understand the PCR mechanism by providing both quantitative information about the reactions and also data to troubleshoot PCRs (e.g., melt curves). Here, we present a relatively short (2-h) laboratory activity to demonstrate qPCR to quantify plasmid copy number (CN) by measuring the cycle threshold (

C
T

) values for a genomic gene and a plasmid gene using transformed cells as a template. The activity can be combined with additional laboratory exercises, including bacterial transformation, to create the template to be used in the qPCRs. This lab activity is ideal for undergraduate laboratory courses that include recombinant DNA technology.
Development of an Online General Biology Open Educational Resource (OER) Laboratory Manual
Authors: Brogun Dmitry Y. , Faucette Azure N. , Polizzotto Kristin , Tamari Farshad
Published: July 2021

Currently, many academic institutions are using one or more variations of online modalities due to the COVID-19 pandemic, and science educators face a unique challenge with distance-learning laboratories. Many resources to engage students in virtual, interactive laboratory activities exist, but we found that high costs and/or overlooked content left gaps for several topics typically taught in a general, introductory biology course for undergraduate biology majors (e.g., organismal biology).
Characterizing Biology Education Research: Perspectives from Practitioners and Scholars in the Field
Authors: Hsu Jeremy L. , Chen Audrey , Cruz-Hinojoza Eduardo , Dinh-Dang Duyen , Roth-Johnson Elizabeth A. , Sato Brian K. , Lo Stanley M.
Published: July 2021

Biology education research (BER) is a recently emerging field mainly focused on the learning and teaching of biology in postsecondary education. As BER continues to grow, exploring what goals, questions, and scholarship the field encompasses will provide an opportunity for the community to reflect on what new lines of inquiry could be pursued in the future.
Antiracist Opportunities in the
Journal of Microbiology and Biology Education
: Considerations for Diversity, Equity, and Inclusion
Authors: Nardi C. L.
Published: July 2021

Authors in the
Journal of Microbiology and Biology Education
(JMBE) have demonstrated a clear commitment to diversity, equity, and inclusion (DEI) through commentaries, instructional approaches, and research. However, analysis of JMBE literature using Kendi’s antiracist framework (
How To Be an Antiracist
, 2019) offers additional opportunities for growth.
The unevenness of the north Iberian crustal root, a snapshot of an elusive stage in margin reactivation
Authors: Fernández-Viejo Gabriela , Cadenas Patricia , Acevedo Jorge , Llana-Fúnez Sergio
Published: July 2021

Crustal roots are identified in collision chains worldwide. Frequently mirroring the summits of mountain systems, they elegantly encapsulate the concept of isostasy. The rugged topography of northern Iberia results from convergence with the European plate during the Alpine orogeny that formed the Pyrenean-Cantabrian mountain range. From east to west, the range comprises three distinct parts: the Pyrenees, the Basque Cantabrian region, and the Cantabrian Mountains. The identification of the Pyrenean root in the 1980s and the observation of a similar geometry beneath the Cantabrian range in the 1990s gave place to the current view of crustal thickening as a continuous feature, resulting from the northward subduction of Iberian crust. Recent developments in rift architecture have delivered a complex rifting template for the area prior to convergence, and contrasting views based on two-dimensional restorations have led to a debate over its evolution. A crucial geophysical constraint is Moho topography. Using two different data sets and techniques, we present the most accurate Moho surface to date, evidencing abrupt changes throughout the orogen. The complexity of hyperextended margins underlies the current Moho topography, and this is ultimately transferred to the nonuniform orogenic pattern found in northern Iberia.
Reactions of Malononitrile Dimer with Isothiocyanates
Authors: Dotsenko V. V. , Bespalov A. V. , Russkikh A. A. , Kindop V. K. , Aksenov N. A. , Aksenova I. V. , Shcherbakov S. V. , Ovcharov S. N .
Published: July 2021

The reaction of 2-amino-1,1,3-tricyanopropene (malononitrile dimer) with
isothiocyanates leads to 1-substituted
4,6-diamino-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitriles or
4,6-diamino-2-(phenylimino)-2H-thiopyran-3,5-dicarbonitrile, depending on the conditions.
Quantum-chemical modeling of the IR spectra and reaction routes for the
synthesized compounds was carried out. In
silico predictive analysis of potential protein targets,
compliance with bioavailability criteria, and ADMET parameters was
performed.
Primary diffuse large B cell lymphoma of the optic chiasm in an immunocompetent patient
Authors: De Jesus Orlando , Rios-Vicil Christian , Gómez-González Frances M , Vélez Román
Published: July 2021

Primary lymphoma of the visual pathway is rare, especially at the chiasm. Very few cases have been reported. The lesion is frequently confused with an optic–hypothalamic glioma. A 55-year-old man was found disoriented at his home by a friend and evaluated with a brain MRI which demonstrated an expansile mass located at the optic chiasm and hypothalamus level. The principal differential was a high-grade hypothalamic glioma due to the contrast enhancement. A biopsy of the chiasmal lesion was performed. Histological diagnosis of the lesion was compatible with a diffuse large B cell lymphoma. He was started on methotrexate and rituximab; however, his clinical course kept deteriorating, and he died 64 days after his presentation. All prior cases of primary lymphoma of the chiasm are reviewed.
Impact of early cholecystectomy on the readmission rate in patients with acute gallstone cholangitis: a retrospective single-centre study
Authors: Hoilat Gilles Jadd , Hoilat Judie Noemie , Abu-Zaid Ahmed , Raleig Julia , Toth Joseph , Mandal Amrenda , Sostre Vanessa , Carvounis Christos , Sapkota Bishnu
Published: July 2021

Background and aims

The pathogenesis of acute cholangitis (AC) occurs with biliary obstruction followed by bacterial growth in the bile duct. The leading cause of AC is obstructing gallstones. There have been conflicting theories about the optimal timing for cholecystectomy following AC. The aim of this study is to assess the impact of early cholecystectomy on the 30-day readmission rate, 30-day mortality, 90-day readmission rate and the length of hospital stay.

Methods

This retrospective study was performed between January 2015 and January 2021 in a high-volume tertiary referral teaching hospital. Included patients were 18 years or older with a definitive diagnosis of acute gallstone cholangitis who underwent endoscopic retrograde cholangiopancreatography (ERCP) with complete clearance of the bile duct as an index procedure. We divided the patients into two groups: patients who underwent ERCP alone and those who underwent ERCP with laparoscopic cholecystectomy (LC) on the same admission (ERCP+LC). Data were extracted from electronic medical records. The primary endpoint of the study was the 30-day readmission rate.

Results

A total of 114 patients with AC met the inclusion criteria of the study. The ERCP+LC group had significantly lower rates of 30-day readmission (2.2% vs 42.6%, p<0.001), 90-day readmission (2.2% vs 30.9%, p<0.001) and 30-day mortality (2.2% vs 16.2%, p=0.017) when compared with the ERCP group. In a multivariate logistic regression analysis, patients in the ERCP+LC group had 90% lower odds of 30-day readmission compared with patients who did not undergo LC during admission (OR=0.1, 95% CI (0.032 to 0.313), p<0.001).

Conclusion

Performing LC on same day admission was associated with a decrease in 30-day and 90-day readmission rate as well as 30-day mortality.
Health expenditures by services and providers for 195 countries, 2000–2017
Authors: Schneider Matthew T , Chang Angela Y , Chapin Abigail , Chen Catherine S , Crosby Sawyer W , Harle Anton C , Tsakalos Golsum , Zlavog Bianca S , Dieleman Joseph L
Published: July 2021

Introduction

National Health Accounts are a significant source of health expenditure data, designed to be comprehensive and comparable across countries. However, there is currently no single repository of this data and even when compiled major gaps persist. This research aims to provide policymakers and researchers with a single repository of available national health expenditures by healthcare functions (ie, services) and providers of such services. Leveraging these data within statistical methods, a complete set of detailed health expenditures is estimated.

Methods

A methodical compilation and synthesis of all available national health expenditure reports including disaggregation by healthcare functions and providers was conducted. Using these data, a Bayesian multivariate regression analysis was implemented to estimate national-level health expenditures by the cross-classification of functions and providers for 195 countries, from 2000 to 2017.

Results

This research used 1662 country-years and 110 070 data points of health expenditures from existing National Health Accounts. The most detailed country-year had 52% of the categories of interest reported. Of all health functions, curative care and medical goods were estimated to make up 51.4% (uncertainty interval (UI) 33.2% to 59.4%) and 17.5% (UI 13.0% to 26.9%) of total global health expenditures in 2017, respectively. Three-quarters of the global health expenditures are allocated to three categories of providers: hospital providers (35.4%, UI 30.3% to 38.9%), providers of ambulatory care (25.5%, UI 21.1% to 28.8%) and retailers of medical goods (14.4%, UI 12.4% to 16.3%). As gross domestic product increases, countries spend more on long-term care and less on preventive care.

Conclusion

Disaggregated estimates of health expenditures are often unavailable and unable to provide policymakers and researchers a holistic understanding of how expenditures are used. This research aggregates reported data and provides a complete time-series of estimates, with uncertainty, of health expenditures by health functions and providers between 2000 and 2017 for 195 countries.
Anticipating the future: prognostic tools as a complementary strategy to improve care for patients with febrile illnesses in resource-limited settings
Authors: Chandna Arjun , Osborn Jennifer , Bassat Quique , Bell David , Burza Sakib , D’Acremont Valérie , Fernandez-Carballo B Leticia , Kain Kevin C , Mayxay Mayfong , Wiens Matthew , Dittrich Sabine
Published: July 2021

In low-income and middle-income countries, most patients with febrile illnesses present to peripheral levels of the health system where diagnostic capacity is very limited. In these contexts, accurate risk stratification can be particularly impactful, helping to guide allocation of scarce resources to ensure timely and tailored care. However, reporting of prognostic research is often imprecise and few prognostic tests or algorithms are translated into clinical practice.

Here, we review the often-conflated concepts of prognosis and diagnosis, with a focus on patients with febrile illnesses. Drawing on a recent global stakeholder consultation, we apply these concepts to propose three use-cases for prognostic tools in the management of febrile illnesses in resource-limited settings: (1) guiding referrals from the community to higher-level care; (2) informing resource allocation for patients admitted to hospital and (3) identifying patients who may benefit from closer follow-up post-hospital discharge. We explore the practical implications for new technologies and reflect on the challenges and knowledge gaps that must be addressed before this approach could be incorporated into routine care settings.

Our intention is that these use-cases, alongside other recent initiatives, will help to promote a harmonised yet contextualised approach for prognostic research in febrile illness. We argue that this is especially important given the heterogeneous settings in which care is often provided for patients with febrile illnesses living in low-income and middle-income countries.
National optimisation of accessibility to emergency obstetrical and neonatal care in Togo: a geospatial analysis
Authors: Curtis Andrew , Monet Jean-Pierre , Brun Michel , Bindaoudou Issa Abdou-Kérim , Daoudou Idrissou , Schaaf Marta , Agbigbi Yawo , Ray Nicolas
Published: July 2021

Objectives

Improving access to emergency obstetrical and neonatal care (EmONC) is a key strategy for reducing maternal and neonatal mortality. Access is shaped by several factors, including service availability and geographical accessibility. In 2013, the Ministry of Health (MoH) of Togo used service availability and other criteria to designate particular facilities as EmONC facilities, facilitating efficient allocation of limited resources. In 2018, the MoH further revised and rationalised this health facility network by applying an innovative methodology using health facility characteristics and geographical accessibility modelling to optimise timely access to EmONC services. This study compares the geographical accessibility of the network established in 2013 and the smaller network developed in 2018.

Design

We used data regarding travel modes and speeds, geographical barriers and topographical and urban constraints, to estimate travel times to the nearest EmONC facilities. We compared the EmONC network of 109 facilities established in 2013 with the one composed of 73 facilities established in 2018, using three travel scenarios (walking and motorised, motorcycle-taxi and walking-only).

Results

When walking and motorised travel is considered, the 2013 EmONC network covers 81% and 96.6% of the population at the 1-hour and 2-hour limit, respectively. These figures are slightly higher when motorcycle-taxis are considered (82.8% and 98%), and decreased to 34.7% and 52.3% for the walking-only scenario. The 2018 prioritised EmONC network covers 78.3% (1-hour) and 95.5% (2-hour) of the population for the walking and motorised scenario.

Conclusions

By factoring in geographical accessibility modelling to our iterative EmONC prioritisation process, the MoH was able to decrease the designated number of EmONC facilities in Togo by about 30%, while still ensuring that a high proportion of the population has timely access to these services. However, the physical access to EmONC for women unable to afford motorised transport remains inequitable.
Using electronic health records to develop and validate a machine-learning tool to predict type 2 diabetes outcomes: a study protocol
Authors: Neves Ana Luisa , Pereira Rodrigues Pedro , Mulla Abdulrahim , Glampson Ben , Willis Tony , Darzi Ara , Mayer Erik
Published: July 2021

Introduction

Type 2 diabetes mellitus (T2DM) is a major cause of blindness, kidney failure, myocardial infarction, stroke and lower limb amputation. We are still unable, however, to accurately predict or identify which patients are at a higher risk of deterioration. Most risk stratification tools do not account for novel factors such as sociodemographic determinants, self-management ability or access to healthcare. Additionally, most tools are based in clinical trials, with limited external generalisability.

Objective

The aim of this work is to design and validate a machine learning-based tool to identify patients with T2DM at high risk of clinical deterioration, based on a comprehensive set of patient-level characteristics retrieved from a population health linked dataset.

Sample and design

Retrospective cohort study of patients with diagnosis of T2DM on 1 January 2015, with a 5-year follow-up. Anonymised electronic healthcare records from the Whole System Integrated Care (WSIC) database will be used.

Preliminary outcomes

Outcome variables of clinical deterioration will include retinopathy, chronic renal disease, myocardial infarction, stroke, peripheral arterial disease or death. Predictor variables will include sociodemographic and geographic data, patients’ ability to self-manage disease, clinical and metabolic parameters and healthcare service usage. Prognostic models will be defined using multidependence Bayesian networks. The derivation cohort, comprising 80% of the patients, will be used to define the prognostic models. Model parameters will be internally validated by comparing the area under the receiver operating characteristic curve in the derivation cohort with those calculated from a leave-one-out and a 10 times twofold cross-validation.

Ethics and dissemination

The study has received approvals from the Information Governance Committee at the WSIC. Results will be made available to people with T2DM, their caregivers, the funders, diabetes care societies and other researchers.
Days alive and at home after hip fracture: a cross-sectional validation of a patient-centred outcome measure using routinely collected data
Authors: McIsaac Daniel I , Talarico Robert , Jerath Angela , Wijeysundera Duminda N
Published: July 2021

Background

Days alive and at home (DAH) is a patient centered outcome measureable in routinely collected health data. The validity and minimally important difference (MID) in hip fracture have not been evaluated.

Objective

We assessed construct and predictive validity and estimated a MID for the patient-centred outcome of DAH after hip fracture admission.

Methods

This is a cross-sectional observational study using linked health administrative data in Ontario, Canada. DAH was calculated as the number of days alive within 90 days of admission minus the number of days hospitalised or institutionalised. All hospital admissions (2012–2018) for hip fracture in adults aged >50 years were included. Construct validity analyses used Bayesian quantile regression to estimate the associations of postulated patient, admission and process-related variables with DAH. The predictive validity assessed was the correlation of DAH in 90 days with the value from 91 to 365 days; and the association and discrimination of DAH in 90 days predicting subsequent mortality. MID was estimated by averaging distribution-based and clinical anchor-based estimates.

Results

We identified 63 778 patients with hip fracture. The median number of DAH was 43 (range 0–87). In the 90 days after admission, 8050 (12.6%) people died; a further 6366 (10.0%) died from days 91 to 365. Associations between patient-level and admission-level factors with the median DAH (lower with greater age, frailty and comorbidity, lower if admitted to intensive care or having had a complication) supported construct validity. DAH in 90 days after admission was strongly correlated with DAH in 365 days after admission (r=0.922). An 11-day MID was estimated.

Conclusion

DAH has face, construct and predictive validity as a patient-centred outcome in patients with hip fracture, with an estimated MID of 11 days. Future research is required to include direct patient perspectives in confirming MID.
Iron deficiency in patients with cancer: a prospective cross-sectional study
Authors: Luporsi Elisabeth , Turpin Anthony , Massard Vincent , Morin Sophie , Chauffert Bruno , Carnot Aurélien , Cacoub Patrice
Published: July 2021

Background

Despite the deleterious consequences of iron deficiency (ID) in patients with cancer, underdiagnosis is frequent. The CARENFER study aimed to assess the prevalence of ID using both serum ferritin concentration and transferrin coefficient saturation (iron-saturation of transferrin, TSAT) index, as well as ID anaemia in patients with cancer.

Methods

This prospective cross-sectional study was conducted in 15 oncology units in France in 2019. All patients present in the medical unit during the 2-week study period, regardless of the type of tumour (solid or haematological) and treatment, were eligible. Serum ferritin concentration, TSAT index and haemoglobin level were determined. ID and ID-associated anaemia were defined according to European Society of Medical Oncology 2018 Guidelines: ID was defined either as ferritin <100 µg/L (absolute ID) or as ferritin ≥100 µg/L and TSAT <20% (functional ID).

Results

A total of 1221 patients with different types of solid malignant tumours were analysed: median age 64 years; 89.4% under treatment for their cancer, mainly by chemotherapy (75.4%). Overall, ID was found in 57.9% (55.1–60.6) of patients. Among them, functional ID accounted for 64% of cases. ID anaemia was reported in 21.8% (19.6–24.2) of all patients with cancer. ID was highly prevalent in untreated (75/130, 57.4%) and non-anaemic (419/775, 54.1%) patients.

Conclusion

This study highlights the high prevalence of ID in patients with cancer, whether or not associated with anaemia or treatment. These results emphasise the need to a better detection and management of ID in cancer, thereby optimising overall patient care.

Trial registration number

ClinicalTrials.gov Identifier:NCT03924271.
Efficacy and sustainability of dialectical behaviour therapy for inpatient adolescents: a follow-up study
Authors: Tebbett-Mock Alison Ann , McGee Madeline , Saito Ema
Published: July 2021

Background

Dialectical behaviour therapy (DBT) is an evidence-based treatment for adolescents targeting suicidal and non-suicidal self-injurious behaviours. Research supports DBT’s efficacy in inpatient settings, but implementation and sustainability are understudied.

Aims

This study is a follow-up of a previous study by Tebbett-Mocket aland examines the efficacy and sustainability of an adolescent DBT inpatient unit within a psychiatric hospital in the Northeast. We hypothesised that adolescents who received DBT in our follow-up group (DBT Group 2) would not have statistical difference (ie, greater or fewer) of the following compared with the first group of patients who received DBT on the unit the year prior (DBT Group 1) and would have significantly fewer of the following compared with the treatment as usual (TAU) group: (1) constant observation hours for suicidal ideation, self-injury and aggression; (2) incidents of suicide attempts, self-injury and aggression; (3) restraints; (4) seclusions; (5) days hospitalised; (6) times readmitted to the unit within 30 days of discharge.

Methods

We conducted a retrospective chart review for adolescents receiving inpatient DBT (DBT Group 1, n=425; DBT Group 2, n=393) and a historical control group (TAU, n=376). The χ2tests and one-way analysis of variance were conducted as preliminary analyses to examine group differences on diagnosis, gender and age. Kruskal-Wallis H tests were conducted to examine group differences on outcomes. Mann-Whitney U tests were used as post hoc analyses.

Results

Patients in DBT Group 2 were comparable to DBT Group 1 for the number of constant observation hours for self-injury (U=83 432.50, p=0.901), restraints (U=82 109, p=0.171) and days hospitalised (U=83 438.5, p=0.956). Patients in DBT Group 2 had a significantly greater number of incidents of suicide attempts compared with DBT Group 1 (U=82 662.5, p=0.037) and of self-injury compared with patients in DBT Group 1 (U=71724.5, p<0.001) and TAU (U=65649.0, p<0.001).

Conclusions

Results provide support for adolescent inpatient DBT compared with TAU and highlight staff turnover and lack of training as potential barriers to sustainability and efficacy.
Pembrolizumab-induced cytokine release syndrome in a patient with metastatic lung adenocarcinoma: a case report
Authors: Sackstein Paul , Zaemes Jacob , Kim Chul
Published: July 2021

Cytokine release syndrome (CRS) is a well-described immune-related adverse event following chimeric antigen receptor T-cell therapy, but has rarely been reported following anti-programmed death ligand-1 therapy. We report the case of a 55-year-old man with metastatic lung adenocarcinoma who presented with fever, chills and hypotension. Initial labs were notable for highly elevated serum ferritin levels and mildly elevated triglyceride levels. He was ultimately diagnosed with pembrolizumab-induced CRS complicated by multiorgan failure. The patient was treated with steroids and tocilizumab with normalization of inflammatory markers and resolution of renal failure. This case not only highlights the importance of considering CRS in patients who have developed multiorgan failure after immune checkpoint inhibitor therapy, but also demonstrates clinical similarities between CRS and other hyperinflammatory states such as hemophagocytic lymphohistiocytosis.
Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial
Authors: Monga Varun , Miller Benjamin J , Tanas Munir , Boukhar Sarag , Allen Bryan , Anderson Carryn , Stephens Laura , Hartwig Stacey , Varga Steven , Houtman Jon , Wang Lei , Zhang Weizhou , Jaber Omar , Thomason Jon , Kuehn David , Rajput Maheen , Metz Catherine , Zamba K.D. , Mott Sarah , Abanonu Chinemerem , Bhatia Sudershan , Milhem Mohammed
Published: July 2021

Background

Soft-tissue sarcomas (STS) in the extremities and trunk treated with standard-of-care preoperative external beam radiation therapy (EBRT) followed by surgical resection are associated with local and distant relapses. In preclinical studies, oncolytic virotherapy in sarcoma has demonstrated antitumor effects via direct intratumoral oncolysis and cytotoxic T-cell–mediated immune responses. Talimogene laherparepvec (TVEC) is a replication-competent, immune-enhanced, oncolytic herpes simplex virus type 1 engineered for intratumoral injection; it has been approved by the FDA for the treatment of locally advanced and metastatic melanoma.

Methods

We explored a novel combination of TVEC with standard-of-care EBRT administered preoperatively in patients with locally advanced STS of the extremities and trunk in a phase IB/II clinical trial. Thirty patients with primary STS >5 cm for which EBRT was indicated to achieve negative margins were enrolled. FDA-approved TVEC doses were used. Immune correlative studies in peripheral blood, biopsy and resected tumor tissues were performed.

Results

No dose-limiting toxicity was observed. Adverse events were similar to those reported in prior studies with TVEC. One patient with myxoid liposarcoma exhibited a partial response. Seven of the 29 (24%) evaluable patients achieved 95% pathological necrosis. None of the patients developed a herpes infection due to the treatment. Eight of the 29 (27%) patients developed postoperative wound complications, which is consistent with previous studies. None of the patients developed local recurrence after surgical resection of the primary sarcoma. 2-year progression-free and overall survival were 57% and 88%, respectively. Caspase-3 demonstrated increased expression of both in TVEC-treated tissue samples as compared with control samples treated with radiation alone.

Conclusion

Preoperative intratumoral TVEC with concurrent EBRT for locally advanced STS is safe and well-tolerated. This combination treatment may enhance immune responses in some cases but did not increase the proposed rate of pathological necrosis. The Caspase-3 biomarker may be associated with a positive effect of TVEC in sarcoma tumor tissue and should be explored in future studies.

Trial registration number

NCT02453191.
‘First Do No Harm’: physician discretion, racial disparities and opioid treatment agreements
Authors: Beck Adrienne Sabine , Svirsky Larisa , Howard Dana
Published: July 2021

The increasing use of opioid treatment agreements (OTAs) has prompted debate within the medical community about ethical challenges with respect to their implementation. The focus of debate is usually on the efficacy of OTAs at reducing opioid misuse, how OTAs may undermine trust between physicians and patients and the potential coercive nature of requiring patients to sign such agreements as a condition for receiving pain care. An important consideration missing from these conversations is the potential for racial bias in the current way that OTAs are incorporated into clinical practice and in the amount of physician discretion that current opioid guidelines support. While the use of OTAs has become mandatory in some states for certain classes of patients, physicians are still afforded great leeway in how these OTAs are implemented in clinical practice and how their terms should be enforced. This paper uses the guidelines provided for OTA implementation by the states of Indiana and Pennsylvania as case studies in order to argue that giving physicians certain kinds of discretion may exacerbate racial health disparities. This problem cannot simply be addressed by minimising physician discretion in general, but rather by providing mechanisms to hold physicians accountable for how they treat patients on long-term opioid therapy to ensure that such treatment is equitable.
Missing data in randomised controlled trials of rheumatoid arthritis drug therapy are substantial and handled inappropriately
Authors: Khan Nasim A , Torralba Karina D , Aslam Fawad
Published: July 2021

Objectives

To analyse the amount, reporting and handling of missing data, approach to intention-to-treat (ITT) principle application and sensitivity analysis utilisation in randomised clinical trials (RCTs) of rheumatoid arthritis (RA). To assess the trend in such reporting 10 years apart (2006 and 2016).

Methods

Parallel group drug therapy RA RCTs with a clinical primary endpoint.

Results

176 studies enrolling a median of 160 (IQR 62–339) patients were eligible. In terms of actual analysis: 81 (46%) RCTs conducted ITT, 42 (23.9%) conducted modified ITT while 53 (30.1%) conducted non-ITT analysis. Only 58 of 97 (59.8%) RCTs reporting an ITT analysis actually performed it. The median (IQR) numbers of participants completing the trial and included in analysis for primary outcome were 86% (74%–91%) and 100% (97.1%–100%), respectively. 53 (32.7%) and 65 (40.1%) RCTs had >20% and 10%–20% missing primary outcome data, respectively. Missing data handling was unreported by 58 of 171 (33.9%) RCTs. When reported, vast majority used simple imputation methods. No significant trend towards improved reporting was seen between 2006 and 2016. Sensitivity analysis numerically improved from 2006 to 2016 (14.7% vs 21.4%).

Conclusions

There is significant discrepancy in the reported and the actual performed analysis in RA drug therapy RCTs. Nearly one-third of RCTs had >20% missing data. The reporting and methods of missing data handling remain inadequate with high usage of non-preferred simple imputation methods. Sensitivity analysis utilisation was low. No trend towards better missing data reporting and handling was seen.