bluuebunny/crossref_metadata_2025 huggingface dataset:
Ebola-Specific CD8+ and CD4+ T-Cell Responses in Sierra Leonean Ebola Virus Survivors With or Without Post-Ebola Sequelae
Authors: LaVergne Stephanie M , Sakabe Saori , Kanneh Lansana , Momoh Mambu , Al-Hassan Foday , Yilah Mohamed , Goba Augustine , Sandi John Demby , Gbakie Michael , Cubitt Beatrice , Boisen Matthew , Mayeux Jessica M , Smira Ashley , Shore Kayla , Bica Iris , Pollard K Michael , Carlos de la Torre Juan , Branco Luis M , Garry Robert F , Grant Donald S , Schieffelin John S , Oldstone Michael B A , Sullivan Brian M
Published: May 2020

Background

Ebola virus (EBOV) disease has killed thousands of West and Central Africans over the past several decades. Many who survive the acute disease later experience post-Ebola syndrome, a constellation of symptoms whose causative pathogenesis is unclear.

Methods

We investigated EBOV-specific CD8+ and CD4+ T-cell responses in 37 Sierra Leonean EBOV disease survivors with (n = 19) or without (n = 18) sequelae of arthralgia and ocular symptoms. Peripheral blood mononuclear cells were infected with recombinant vesicular stomatitis virus encoding EBOV antigens. We also studied the presence of EBOV-specific immunoglobulin G, antinuclear antibodies, anti–cyclic citrullinated peptide antibodies, rheumatoid factor, complement levels, and cytokine levels in these 2 groups.

Results

Survivors with sequelae had a significantly higher EBOV-specific CD8+ and CD4+ T-cell response. No differences in EBOV-specific immunoglobulin G, antinuclear antibody, or anti–cyclic citrullinated peptide antibody levels were found. Survivors with sequelae showed significantly higher rheumatoid factor levels.

Conclusion

EBOV-specific CD8+ and CD4+ T-cell responses were significantly higher in Ebola survivors with post-Ebola syndrome. These findings suggest that pathogenesis may occur as an immune-mediated disease via virus-specific T-cell immune response or that persistent antigen exposure leads to increased and sustained T-cell responses.
Chronic and Early Antiretroviral Therapy Impact Human Immunodeficiency Virus (HIV) Serological Assay Sensitivity, Leading to More False-Negative Test Results in HIV Diagnosis
Authors: Stoffels Karolien , Vanroye Fien , Mortier Virginie , Debaisieux Laurent , Delforge Marie-Luce , Depypere Melissa , Dessilly Géraldine , Vaira Dolores , Vancutsem Ellen , Van den Wijngaert Sigi , Van Laethem Kristel , Vercauteren Koen O A , Verhofstede Chris , Fransen Katrien
Published: May 2020

This retrospective study evaluated the reactivity of 3 human immunodeficiency virus (HIV) confirmatory assays (INNO-LIA, Geenius, and MP) and 7 HIV rapid tests on samples from 2 different study populations in Belgium. For the early-treated cohort (83 HIV-1 adult patients treated within 3 months after infection), HIV-1 diagnosis was not obtained in at least 1 confirmatory assay in 12.0% (10/83) and in an HIV rapid test in 31.3% (26/83). Confirmation assay sensitivities ranged from 87.5% to 95.2%, whereas rapid test assay sensitivities ranged from 75.9% to 100%. The time to treatment initiation or the length of time on treatment did not have a statistical influence on the probability to obtain a false-negative test result. The fastest reversion was demonstrated after 4 months of treatment. Among the long-term treated cohort (390 HIV-1 patients with ≥ 9 years of undetectable viral load), false-negative test results were found in at least 1 HIV confirmatory assay for 2.1% (8/390) of the patients and in a HIV rapid test for 4.9% (19/390). Confirmation assay sensitivities ranged from 98.1% to 99.5%, whereas rapid test sensitivities ranged from 96.2% to 100%. Longer treatment increased nonreactivity of the HIV rapid tests (P = .033). Undetectable viral load decreases the sensitivities of HIV diagnostic tests, and further monitoring of the performance of serological assays is advised.
Understanding Meaningful Participation and the Situated Use of Technology in Community Music for Active Ageing
Authors: Mao Mao , Blackwell Alan F , Good David A
Published: May 2020

An unfortunate tendency in previous HCI research has been to give the impression that it aims to ‘fix the problem’ of human ageing, suggesting a ‘deficit’ model of ageing or a ‘prosthetic’ model of technology. We conducted diary-aided interviews to investigate how technology use is situated in active, healthy older adults’ meaningful participation in community music. We argue that recognizing community music practices and technology use as situated action provides opportunities to grasp the subtleties of social participation and design for active ageing. We identified technology-mediated music practices, such as music sharing and revisiting, and how they evolved through the reconfiguration of connections between technology, competence, and forward-facing identities. We found that identity development, via routes such as exercising control, role transitions, and social spaces, had psychological significance and implications for active ageing. We explore how HCI leverages the perspective of active ageing and might facilitate older adults’ meaningful participation enhanced by technologies.
Pharmacokinetic similarity demonstrated after crushing of the elbasvir/grazoprevir fixed-dose combination tablet for HCV infection
Authors: Pijnenburg Daniëlle W M , van Seyen Minou , Abbink Evertine J , Colbers Angela , Drenth Joost P H , Burger David M
Published: May 2020

Background

Finding a suitable treatment for HCV patients with swallowing disorders is still a major challenge. In practice, direct-acting antivirals are crushed without knowledge of adequate absorption. Crushing can alter drug exposure, possibly leading to treatment failure, development of resistance or toxicity. Currently, there is no information about crushing of the fixed-dose combination tablet of elbasvir/grazoprevir; therefore, crushing of this tablet is not recommended.

Objectives

To investigate the influence of crushing on the pharmacokinetics of the elbasvir/grazoprevir fixed-dose combination tablet.

Methods

We conducted an open-label, two-period, randomized, cross-over, Phase I, single-dose trial in 11 healthy adult volunteers. Subjects randomly received whole-tablet elbasvir/grazoprevir or crushed and suspended elbasvir/grazoprevir in a fasted state. Pharmacokinetic similarity criteria (90% CIs lie within 70%–143% acceptance range) were used for AUC0–∞ and AUC0–72.

Results

Mean plasma concentration–time curves of elbasvir and grazoprevir showed similar pharmacokinetic profiles. The primary pharmacokinetic parameters AUC0–∞ and AUC0–72 of elbasvir and grazoprevir after intake of a crushed tablet were on average 12%–16% higher compared with the whole tablet, but 90% CIs were all within the predefined boundaries of pharmacokinetic similarity. Crushing leads to a higher Cmax of grazoprevir (42%); no significant difference was found between treatments with regard to the Cmax of elbasvir. No serious adverse events were reported during the trial.

Conclusions

Pharmacokinetic similarity could be demonstrated for a crushed and suspended tablet compared with a whole tablet, without impacting drug safety or efficacy. Crushed and suspended administration of elbasvir/grazoprevir can be used in patients with swallowing disorders.
Carbapenem inactivation method using bacterial lysate and MOPS (LCIM): a very sensitive method for detecting carbapenemase-producing Acinetobacter species
Authors: Yamada Kageto , Aoki Kotaro , Nagasawa Tatsuya , Imai Waka , Sasaki Masakazu , Murakami Hinako , Morita Toshisuke , Ishii Yoshikazu , Tateda Kazuhiro
Published: May 2020

Objectives

Detection of carbapenem-hydrolysing class D β-lactamase (CHDL)-producing Acinetobacter spp. is critical for understanding antibiotic resistance. In this study, we compared the available detection techniques derived from the carbapenem inactivation method (CIM), using CHDL-producing Acinetobacter spp., and developed a modified method that uses bacterial lysate (lysate CIM; LCIM).

Methods

A total of 159 Acinetobacter spp. (102 carbapenemase producers and 57 non-producers) and 14 Pseudomonas spp. (7 carbapenemase producers and 7 non-producers) were tested. Modified CIM, simplified CIM, CIMTris, Triton-CIM and LCIM were compared using these strains. Distinct from the CIM, LCIM includes a longer incubation period (4 h) with 2.0% Triton X-100 (v/v) in 20 mM MOPS buffer instead of water.

Results

The sensitivity/specificity of the modified CIM, simplified CIM, CIMTris, Triton-CIM and LCIM were 71.6%/100%, 66.1%/89.1%, 88.1%/95.3%, 80.7%/100% and 97.2%/100%, respectively. LCIM was the most sensitive and specific.

Conclusions

Use of bacterial lysate and MOPS increased the sensitivity of the CIM in detecting CHDL-producing Acinetobacter spp.
Palliative care physicians’ perspectives of management for terminally ill cancer patients with death rattle: a nationwide survey
Authors: Matsunuma Ryo , Suzuki Kozue , Matsuda Yoshinobu , Mori Masanori , Watanabe Hiroaki , Yamaguchi Takashi
Published: May 2020

Death rattle occurs during the last days of life, and relatives of those afflicted frequently report that it is very distressful. However, there is no effective treatment for it. The purpose of this study was to investigate the perceptions of Japanese palliative care physicians in clinical practice in Japan. We conducted a nationwide survey of 268 physicians via an anonymous, self-report questionnaire. We assessed pharmacological and non-pharmacological management and anticholinergic agent choice. One hundred eighty-nine physicians (70.5%) returned the questionnaires. Fifty-five participants (29.1%) treating patients with Type-1 (real death rattle) and 36 participants (19%) treating patients with Type-2 (pseudo-death rattle) death rattle reported that they would frequently administer an anticholinergic agent. One-fourth would administer scopolamine butylbromide or scopolamine hydrobromide. In conclusion, more Japanese palliative care physicians thought that anticholinergic agents might be effective for treating Type-1 death rattle rather than Type-2. Further clinical trials of these agents are needed.
A Dozen Testosterone Samples From One Patient, on One Day?
Authors: Foley Kevin F
Published: May 2020

The differential diagnosis of female virilization and infertility can be significantly narrowed using routine laboratory testing. The case presented herein is an example of a 28 year old Caucasian female patient with amenorrhea, hirsutism, and infertility in the context of markedly elevated serum testosterone levels. This case highlights the use of bilateral ovarian vein sampling for testosterone as a means to localize the ectopic testosterone production and to guide future surgical procedures. Adrenal vein sampling procedures are relatively more common than other methods. Ovarian vein sampling is less common, yet in this case, it proved diagnostic. This case demonstrates the needed cooperation of the clinical laboratory and the patient care team performing the catheterization, for this type of testing to be useful. In this unique case, we discovered bilateral production of androgens.
Assessment of Medical Laboratory Undergraduates Training in Different School Year Systems
Authors: Lu Yajun , Xia Qianfeng , Yang Jun
Published: May 2020

Objective

To assess the effect of the change from the 5-year system of coursework to a 4-year system on the achievements of medical laboratory undergraduates.

Methods

We analyzed and then compared the topics of training and the test scores among all subject individuals in the 5-year vs the 4-year undergraduate program.

Results

Five-year-program undergraduates and 4-year-program undergraduates were required to complete 50 courses. The average weekly education time in the 4-year program (27.05 lesson-hours/week) was greater than that in the 5-year program (22.99 lesson-hours/week). The proportion of clinical practice in the hospital setting in the 4-year program (26.8%) was higher than that in the 5-year program (24.5%). The average, excellent, and good scores among 4-year-program undergraduates in general education courses, professional basic courses, professional courses, all courses, and common courses were lower than those scores among the 5-year-program undergraduates.

Conclusions

The 5-year undergraduate program should be adapted to help boost the achievements and practical skills among its students, in helping them adapt quickly to the new, 4-year training plan (which presented a serious challenge in our cohort).
Revising the merger scenario of the galaxy cluster Abell 1644: a new gas poor structure discovered by weak gravitational lensing
Authors: Monteiro-Oliveira R , Doubrawa L , Machado R E G , Lima Neto G B , Castejon M , Cypriano E S
Published: May 2020

The galaxy cluster Abell 1644 ($\bar{z}=0.047$) is known for its remarkable spiral-like X-ray emission. It was previously identified as a bimodal system, comprising the subclusters, A1644S and A1644N, each one centred on a giant elliptical galaxy. In this work, we present a comprehensive study of this system, including new weak lensing and dynamical data and analysis plus a tailor-made hydrodynamical simulation. The lensing and galaxy density maps showed a structure in the North that could not be seen on the X-ray images. We, therefore, rename the previously known northern halo as A1644N1 and the new one as A1644N2. Our lensing data suggest that those have fairly similar masses: $M_{200}^{\rm N1}=0.90_{-0.85}^{+0.45} \times 10^{14}$ and $M_{200}^{\rm N2}=0.76_{-0.75}^{+0.37} \times 10^{14}$ M⊙, whereas the southern structure is the main one: $M_{200}^{\rm S}=1.90_{-1.28}^{+0.89}\times 10^{14}$ M⊙. Based on the simulations, fed by the observational data, we propose a scenario where the remarkable X-ray characteristics in the system are the result of a collision between A1644S and A1644N2 that happened ∼1.6 Gyr ago. Currently, those systems should be heading to a new encounter, after reaching their maximum separation.
A solution to the overdamping problem when simulating dust–gas mixtures with smoothed particle hydrodynamics
Authors: Price Daniel J , Laibe Guillaume
Published: May 2020

We present a fix to the overdamping problem found by Laibe & Price when simulating strongly coupled dust–gas mixtures using two different sets of particles using smoothed particle hydrodynamics. Our solution is to compute the drag at the barycentre between gas and dust particle pairs when computing the drag force by reconstructing the velocity field, similar to the procedure in Godunov-type solvers. This fixes the overdamping problem at negligible computational cost, but with additional memory required to store velocity derivatives. We employ slope limiters to avoid spurious oscillations at shocks, finding the van Leer Monotonized Central limiter most effective.
Downregulation of HDAC8 expression decreases CD163 levels and promotes the apoptosis of macrophages by activating the ERK signaling pathway in recurrent spontaneous miscarriage
Authors: Yao Yongli , Hao Fan , Tang Lin-Chen , Xu Xiang-Hong , Jin Liping
Published: May 2020

Recurrent spontaneous miscarriage (RSM) is a systemic disorder that has been defined as two or more pregnancies lost before the 20th week of gestation. Although the impaired function of macrophages at the maternal–fetal interface has been reported to be associated with RSM, the underlying mechanisms have not been fully elucidated. Here, we revealed that HDAC8 plays a critical role in RSM. Our results show that the mRNA and protein expression of HDAC8 was decreased in decidual macrophages from RSM patients. Moreover, the knockdown of HDAC8 resulted in a significant decrease in CD163 expression and an increase in apoptosis in dTHP-1 macrophages. Mechanistically, the ERK signaling pathway was activated in HDAC8-knockdown macrophages. When HDAC8-knockdown cells were pretreated with the ERK inhibitor U0126, expression levels of CD163, activated caspases 3, 7 and 9, and the apoptosis rate, were rescued. Taken together, our current results suggest that HDAC8 plays an important role in macrophage activation and apoptosis and may contribute to maintaining normal pregnancy by increasing the expression of M2 marker genes and inhibiting the apoptosis of macrophages at the maternal–fetal interface.
RiboToolkit: an integrated platform for analysis and annotation of ribosome profiling data to decode mRNA translation at codon resolution
Authors: Liu Qi , Shvarts Tanya , Sliz Piotr , Gregory Richard I
Published: May 2020

Ribosome profiling (Ribo-seq) is a powerful technology for globally monitoring RNA translation; ranging from codon occupancy profiling, identification of actively translated open reading frames (ORFs), to the quantification of translational efficiency under various physiological or experimental conditions. However, analyzing and decoding translation information from Ribo-seq data is not trivial. Although there are many existing tools to analyze Ribo-seq data, most of these tools are designed for specific or limited functionalities and an easy-to-use integrated tool to analyze Ribo-seq data is lacking. Fortunately, the small size (26–34 nt) of ribosome protected fragments (RPFs) in Ribo-seq and the relatively small amount of sequencing data greatly facilitates the development of such a web platform, which is easy to manipulate for users with or without bioinformatic expertise. Thus, we developed RiboToolkit (http://rnabioinfor.tch.harvard.edu/RiboToolkit), a convenient, freely available, web-based service to centralize Ribo-seq data analyses, including data cleaning and quality evaluation, expression analysis based on RPFs, codon occupancy, translation efficiency analysis, differential translation analysis, functional annotation, translation metagene analysis, and identification of actively translated ORFs. Besides, easy-to-use web interfaces were developed to facilitate data analysis and intuitively visualize results. Thus, RiboToolkit will greatly facilitate the study of mRNA translation based on ribosome profiling.
Clinical Characteristics, Etiology, and Initial Management Strategy of Newly Diagnosed Periprosthetic Joint Infection: A Multicenter, Prospective Observational Cohort Study of 783 Patients
Authors: Manning Laurens , Metcalf Sarah , Clark Benjamin , Robinson James Owen , Huggan Paul , Luey Chris , McBride Stephen , Aboltins Craig , Nelson Renjy , Campbell David , Solomon Lucian Bogdan , Schneider Kellie , Loewenthal Mark , Yates Piers , Athan Eugene , Cooper Darcie , Rad Babak , Allworth Tony , Reid Alistair , Read Kerry , Leung Peter , Sud Archana , Nagendra Vana , Chean Roy , Lemoh Chris , Mutalima Nora , Grimwade Kate , Sehu Marjorie , Torda Adrienne , Aung Thi , Graves Steven , Paterson David , Davis Josh
Published: May 2020

Background

Periprosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Most observational studies of PJI are retrospective or single-center, and reported management approaches and outcomes vary widely. We hypothesized that there would be substantial heterogeneity in PJI management and that most PJIs would present as late acute infections occurring as a consequence of bloodstream infections.

Methods

The Prosthetic joint Infection in Australia and New Zealand, Observational (PIANO) study is a prospective study at 27 hospitals. From July 2014 through December 2017, we enrolled all adults with a newly diagnosed PJI of a large joint. We collected data on demographics, microbiology, and surgical and antibiotic management over the first 3 months postpresentation.

Results

We enrolled 783 patients (427 knee, 323 hip, 25 shoulder, 6 elbow, and 2 ankle). The mode of presentation was late acute (>30 days postimplantation and <7 days of symptoms; 351, 45%), followed by early (≤30 days postimplantation; 196, 25%) and chronic (>30 days postimplantation with ≥30 days of symptoms; 148, 19%). Debridement, antibiotics, irrigation, and implant retention constituted the commonest initial management approach (565, 72%), but debridement was moderate or less in 142 (25%) and the polyethylene liner was not exchanged in 104 (23%).

Conclusions

In contrast to most studies, late acute infection was the most common mode of presentation, likely reflecting hematogenous seeding. Management was heterogeneous, reflecting the poor evidence base and the need for randomized controlled trials.
Parliamentary Procedure under Theresa May: Nothing Has Changed?
Authors: Fleming Thomas G
Published: May 2020

During the premiership of Theresa May, parliamentary procedure in the UK was scrutinised, criticised and challenged to an extent unprecedented in recent years. This put intense pressure on the ‘rules of the game’ governing parliamentary politics. This article thus aims to answer three questions. First, what were the pressures on parliamentary procedure in this period? Secondly, what were their consequences? Thirdly, how can these consequences be explained? The article addresses these questions by describing challenges to the House of Commons’ rules regarding agenda control, proxy voting and private members’ bills. It also describes the procedural changes resulting from these challenges and evaluates their significance. Finally, it considers how far these changes support the expectations of existing literature on parliamentary rule changes. Overall, the article shows that procedural reform during Theresa May’s premiership was minimal. Despite some temporary informal innovations, the formal rules of the Commons remained almost entirely unchanged. During this period, therefore, Britain’s parliamentary rules were challenged extensively but changed very little.
The substantial awareness role of web-based and social media platforms in developing countries during a pandemic scenario: the example of COVID-19
Authors: Abdul-Baki Mohammad-Nasan , Dhemesh Yaseen , Alasadi Lugien , Alsuliman Tamim
Published: May 2020

Background

During the outbreak of coronavirus COVID-19, social media platforms have shown effectiveness in information dissemination. Delivering evidence-based medical knowledge and trustworthy recommendations is a difficult mission for classical entities, especially in a war-torn country with a fragile health system. In this context, the role of non-governmental scientific organizations was proven, filling the gap between original scientific sources and a non-English speaking population.

Methods

We reviewed an example of an organization named Syrian Researchers, which publishes based-on-reliable-sources of scientific content and has massive reachability across Middle East and beyond.

Results

We strongly believe that this model is a simple and suitable approach that may be helpful for other low-income or war-torn countries in the context of health-related disasters.

Conclusions

This subject is of high importance and we believe that this approach may ameliorate public health knowledge, thus, participate in defying the COVID-19 consequences.
CHARACTERISATION OF RADIOPHOTOLUMINESCENCE DOSIMETRY SYSTEM FOR INDIVIDUAL MONITORING
Authors: Hajek M , Sugiyama M , Kolb G , Tucker D M , Pinak M
Published: May 2020

Performance evaluation is typically assessed as part of the approval procedure to verify that a dosimetry system fulfils specified national or international type-test requirements under representative exposure conditions that are expected to mimic workplace fields from the radiological activities being monitored. The International Atomic Energy Agency Radiation Safety Technical Services Laboratory has recently implemented an integrated radiophotoluminescence (RPL) personal dosimetry system developed by Chiyoda Technol Corporation. This paper reports on the successful verification of dosimetric performance properties of the RPL dosimetry system to IEC 62387:2020, in which the badges were exposed to a range of radiation energies and angles of incidence as well as other influence parameters. Characteristics under test included the coefficient of variation, non-linearity of response due to dose dependence as well as the energy and angular response to photon and beta radiation.
RESPONSE OF CURRENT PHOTON PERSONAL DOSEMETERS TO NEW OPERATIONAL QUANTITIES
Authors: Ekendahl Daniela , Čemusová Zina , Kurková Dana , Kapuciánová Michaela
Published: May 2020

The ICRU proposed new operational quantities, which are defined in close relation to effective dose and absorbed dose. Most of the current personal dosemeters were designed to measure personal dose equivalents. Because of differences between the new and old quantities, the existing dosemeters may not be ideal for measurements of the new quantities, personal dose, Hp, and absorbed dose in local skin, Dp local skin. For photon radiation sources, we investigated relative responses of the current personal dosemeters with respect to the measurement of the new quantities. Introduction of the new quantities into practice will require some changes in practical radiation protection. A recalibration of the current dosemeters will be essential for Hp measurements in higher photon energy region (>50 keV). For lower photon energies, a redesign of specific evaluation algorithms will be necessary. For purposes of Dp local skin measurements the dosemeters do not require any fundamental changes.
Reforms to the Legal Framework of Child Sexual Abuse in India: Legislative Band-Aids on Systemic Wounds
Authors: Chaudhary Shraddha
Published: May 2020

The Criminal Law (Amendment) Act, 2018 and the Protection of Children from Sexual Offences (Amendment) Act, 2019 were purportedly aimed at strengthening the criminal justice system and deterring child sexual abuse. The article demonstrates how both legislations were reactionary, enacted without considering the evidence available on the lacunae in the system they sought to reform. It problematizes and critiques the new offences and enhanced sentences anchored in age-categorizations, the increased mandatory minimum sentences, the unenforceable timelines for investigation and trial, and the reinforcement of the link between fines imposed on the offender and compensation for the victim. It argues that the new legal framework will only exacerbate the implementation hurdles of the old framework, leading to poorer prosecution outcomes. The article also critiques the introduction of the death penalty for child rape. It is argued that the move could expose victims to mortal danger and will create a baffling situation for Special Courts adjudicating de facto consensual cases. While the government touts these legislations as proof of its hard stance on child sexual abuse, this article demonstrates that they were nothing more than political gimmicks, meant to distract from the conspicuous absence of any effort towards systemic change.
Therapeutic drug monitoring in patients on biologics: lessons from gastroenterology
Authors: Papamichael Konstantinos , Cheifetz Adam S.
Published: May 2020

Purpose of review

To give an overview on the role of therapeutic drug monitoring (TDM) of biologics in patients with inflammatory bowel disease (IBD).

Recent findings

Numerous prospective exposure–response relationship studies and post-hoc analyses of randomized controlled trials (RCTs) show a positive correlation between biologic drug concentrations and favorable clinical outcomes in IBD. These studies also demonstrate that higher drug concentrations appear to be needed to achieve more stringent objective therapeutic outcomes. Reactive TDM rationalizes the management of primary nonresponse and secondary loss of response to antitumor necrosis factor (anti-TNF) therapy and is more cost-effective when compared with empiric dose optimization. Furthermore, recent data suggest that proactive TDM, with the goal of targeting a threshold drug concentration, is associated with better therapeutic outcomes when compared with empiric dose escalation and/or reactive TDM of infliximab or adalimumab. Finally, proactive TDM can also efficiently guide infliximab de-escalation or discontinuation in patients with IBD in remission.

Reactive TDM is currently considered as standard of care, whereas proactive TDM is emerging as a new therapeutic strategy for better optimizing anti-TNF therapy in IBD. However, more data from prospective studies are needed before a wide implementation of TDM-based algorithms in real life clinical practice for newer biologics.
The management of enthesitis in clinical practice
Authors: Koppikar Sahil , Eder Lihi
Published: May 2020

Purpose of review

Enthesitis is a hallmark feature of the spondyloarthropathies (SpA). This review provides an overview of recent insights on diagnosis and management of enthesitis.

Recent findings

Recent studies support the use of imaging for diagnosis because of its higher sensitivity and specificity compared with clinical examination. Several new MRI and ultrasound scoring systems have been developed for enthesitis, which may facilitate the use of imaging in research. Enthesitis has been evaluated as a primary study outcome mainly in psoriatic arthritis (PsA); however, the use of different indices and definitions of improvement limits comparison across studies. There is very limited information about the efficacy of synthetic disease modifying antirheumatic drugs (DMARDs) for the treatment of enthesitis. In contrast, targeted and biologic DMARDs have all shown efficacy in treating enthesitis compared with placebo. There have been only a few head-to-head trials that compared two different cytokine inhibitors for the treatment of enthesitis. Preliminary data suggest that targeting IL-17 or IL12/23 may be more efficacious for controlling enthesitis than TNF inhibition.

Emerging data suggest interleukin-17 and 12/23 inhibitors may be the first choice in PsA patients with enthesitis. Further head-to-head studies are needed before making definitive recommendations.
Barrier lymphocytes in spondyloarthritis
Authors: Berlinberg Adam , Kuhn Kristine A.
Published: May 2020

Purpose of review

The clinical overlap between spondyloarthritis (SpA) and inflammation of barrier tissues such as the intestine and skin indicates a role of barrier tissue immunity in the development of SpA. Herein, we review the recent advances in understanding lymphocyte populations and functions within the intestine and skin implicated in the pathophysiology of SpA.

Recent findings

A number of unique lymphocyte populations have been identified to be expanded within the gut and skin of patients with SpA, including γδ T cells, mucosa-associated invariant T (MAIT) cells, innate lymphoid cells (ILCs) and T resident memory (TRM) cells. These cells respond to microbial cues at their barrier surface causing cellular activation and generation of interleukin (IL)-17, which is hypothesized to be the mechanism by which they contribute to SpA pathogenesis.

Understanding how unique lymphocyte populations expand and produce IL-17 in the development of SpA provides insights into the pathophysiology of this disease as well as potential future therapeutic avenues.
The IL-23/IL-17A axis in spondyloarthritis: therapeutics informing pathogenesis?
Authors: Siebert Stefan , McGucken Andrew , McInnes Iain B.
Published: May 2020

Purpose of review

To give an overview of the recently published trials relating to IL-23/IL-17 pathway in spondyloarthritis (SpA).

Recent findings

Recent studies in psoriasis confirmed the efficacy of targeting the IL-23/IL-17 pathway, with emerging evidence from head-to-head studies suggesting functional hierarchy of these inhibitors. In psoriatic arthritis (PsA), recent studies have indicated the efficacy of inhibiting IL-23p19, in addition to IL-23p40 and IL-17A, albeit all with lower hurdle results than those seen in psoriasis. The first head-to-head study of an IL-17A and tumour necrosis factor inhibitor in PsA has also recently been published. Recent studies have demonstrated the efficacy of the IL-17A inhibitor, ixekizumab, across the axial SpA spectrum. In contrast, inhibition of IL-12/IL-23p40 and IL-23p19 both failed in axial SpA. In inflammatory bowel disease (IBD), recent studies indicate efficacy of IL-23p40 and IL-23p19 inhibition, in contrast to the previous failed studies of IL-17 inhibition.

Clinical trials of IL-23/IL-17 inhibition have been transformative in psoriasis, with more mixed results in PsA and differential responses in axial SpA and IBD. These results pose challenges to our fundamental understanding of SpA pathogenesis and further head-to-head studies and more subtle evaluation of the local tissue-specific aspects will be required.
MHC class I associations beyond HLA-B27: the peptide binding hypothesis of psoriatic arthritis and its implications for disease pathogenesis
Authors: Winchester Robert , FitzGerald Oliver
Published: May 2020

Purpose of review

To provide an overview of the heterogeneous human leucocyte antigen (HLA) associations of psoriatic arthritis, their relationship to particular clinical features of the disease, and how a hypothesis of binding specific peptides could provide a unifying basis for this heterogeneity.

Recent findings

There have been substantive advances in understanding the role of HLA molecules in binding self-peptides that select our repertoire of T cells, the specific peptide-binding properties of these HLA allotypes, and their crystallographic structure. These advances provide a means to envision the significance of the heterogeneous psoriatic arthritis HLA associations. The clinical relevance of these allotypes if heightened by emerging knowledge of their relationship to particular clinical features of the disease that serve as subphenotypes.

We propose a peptide binding hypothesis of psoriatic arthritis based on a shared pattern of negative charge in the ‘B’ pocket of the HLA-B and HLA-C molecules encoded by the susceptibility allotypes. This hypothesis suggests that peptides characterized by the presence of arginine at position 2 or 3 are bound to the susceptibility allotypes and drive the T-cell clones selected on them to attack molecules containing these peptides located in sites of psoriatic arthritis inflammation.
Biosimilars in supportive care
Authors: Foreman Emma
Published: May 2020

Purpose of review

This review covers recent publications relating to the use of biosimilar medicines in the supportive care of cancer patients, and broader publications focussed on the benefits and challenges of implementing biosimilars into clinical practice.

Recent findings

A metaanalysis and a number of systematic literature reviews have confirmed that the safety and efficacy of biosimilar versions of epoetin-α, filgrastim and infliximab are equivalent to those of their corresponding reference biologics. New guidelines have been issued concerning the interchangeability of biosimilars and the practice of substituting a biosimilar in place of a prescribed reference product. The introduction of biosimilars into a health system has been shown to improve patient access to treatment while also delivering cost savings, however, there are a number of barriers that can prevent or delay the adoption of biosimilars into clinical practice which must be overcome for the potential benefits of biosimilars to be realized.

There is a large amount of data to demonstrate that supportive care biosimilars are well tolerated and effective, with over 10 years of experience in Europe. We can learn from the challenges faced when introducing biosimilars into supportive care to facilitate the introduction of newer biosimilars into the treatment setting.
Techniques of noncircular corneal transplantation
Authors: Deshmukh Rashmi , Stevenson Louis J. , Vajpayee Rasik B.
Published: May 2020

Purpose of review

The management of peripheral corneal diseases, including Mooren's ulcer, Terrien's marginal degeneration, peripheral ulcerative keratitis and pellucid marginal degeneration is challenging. Circular grafts must either be very large, resulting in the excision of healthy tissue, or eccentric, leading to high levels of astigmatism. This review summarizes the range of noncircular keratoplasty procedures available to surgeons, in addition to their indications, and surgical techniques.

Recent findings

Noncircular grafts have been demonstrated to be useful in the management of peripheral corneal diseases. They are effective at providing tectonic support and also facilitate visual rehabilitation. Specifically, they produce favourable postoperative visual and astigmatic outcomes. The evidence relating to these procedures is largely limited to case reports and case series, with no large-scale studies available.

Noncircular keratoplasty procedures are useful in the management of peripheral corneal diseases, which is typically difficult. There is a need for larger studies to investigate the relative advantages and disadvantages of these procedures and further characterize their outcomes.
Immunodeficiency and inborn disorders of vitamin B12 and folate metabolism
Authors: Watkins David , Rosenblatt David S.
Published: May 2020

Purpose of review

Immune dysfunction, including severe combined immunodeficiency, has been described in genetic disorders affecting the metabolism of the vitamins cobalamin (vitamin B12) and folate. We have reviewed reports of clinical findings in patients with a number of inborn errors of cobalamin or folate metabolism, specifically looking for immune problems.

Recent findings

There is little evidence that immune function is affected in most of the disorders. Exceptions are Imerslund–Gräsbeck syndrome and hereditary folate malabsorption (affecting intestinal absorption of cobalamin and folate, respectively), transcobalamin deficiency (affecting transport of cobalamin in blood and cellular cobalamin uptake), and methylenetetrahydrofolate dehydrogenase 1 deficiency (catalyzing cytoplasmic interconversion of reduced folate coenzyme derivatives).

Although some inborn errors of cobalamin or folate can be associated with immune dysfunction, the degree and type of immune dysfunction vary with no obvious pattern.
The Early Impact of the Centers for Medicare & Medicaid Services State Innovation Models Initiative on 30-Day Hospital Readmissions Among Adults With Diabetes
Authors: Rodríguez Hector P. , Fulton Brent D. , Phillips Aryn Z.
Published: May 2020

Background:

The Centers for Medicare & Medicaid Services (CMS) State Innovation Models (SIM) Initiative funds states to accelerate delivery system and payment reforms. All SIM states focus on improving diabetes care, but SIM’s effect on 30-day readmissions among adults with diabetes remains unclear.

Methods:

A quasi-experimental research design estimated the impact of SIM on 30-day hospital readmissions among adults with diabetes in 3 round 1 SIM states (N=671,996) and 3 comparison states (N=2,719,603) from 2010 to 2015. Difference-in-differences multivariable logistic regression models that incorporated 4-group propensity score weighting were estimated. Heterogeneity of SIM effects by grantee state and for CMS populations were assessed.

Results:

In adjusted difference-in-difference analyses, SIM was associated with an increase in odds of 30-day hospital readmission among patients in SIM states in the post-SIM versus pre-SIM period relative to the ratio in odds of readmission among patients in the comparison states post-SIM versus pre-SIM (ratio of adjusted odds ratio=1.057, P=0.01). Restricting the analyses to CMS populations (Medicare and Medicaid beneficiaries), resulted in consistent findings (ratio of adjusted odds ratio=1.057, P=0.034). SIM did not have different effects on 30-day readmissions by state.

Conclusions:

We found no evidence that SIM reduced 30-day readmission rates among adults with diabetes during the first 2 years of round 1 implementation, even among CMS beneficiaries. It may be difficult to reduce readmissions statewide without greater investment in health information exchange and more intensive use of payment models that promote interorganizational coordination.
Reduced Cost-sharing for Preventive Drugs Preferentially Benefits Low-income Patients With Diabetes in High Deductible Health Plans With Health Savings Accounts
Authors: Ross-Degnan Dennis , Wallace Jamie , Zhang Fang , Soumerai Stephen B. , Garabedian Laura , Wharam J. Frank
Published: May 2020

Background:

High deductible health plans linked to Health Savings Accounts (HSA-HDHPs) must include all care under the deductible except for select preventive services. Some employers and insurers have adopted Preventive Drug Lists (PDLs) that exempt specific classes of medications from deductibles.

Objective:

The objective of this study was to examine the association between shifts to PDL coverage and medication utilization among patients with diabetes in HSA-HDHPs.

Research Design:

A natural experiment comparing pre-post changes in monthly and annual outcomes in matched study groups.

Subjects:

The intervention group included 1744 commercially-insured HSA-HDHP patients with diabetes age 12–64 years switched by employers to PDL coverage; the control group included 3349 propensity-matched HSA-HDHP patients whose employers offered no PDL.

Measures:

Outcomes were out-of-pocket (OOP) costs for medications and the number of pharmacy fills converted to 30-day equivalents.

Results:

Transition to the PDL was associated with a relative pre-post decrease of $612 (−35%,P<0.001) per member OOP medication expenditures; OOP reductions were higher for key classes of antidiabetic and cardiovascular medicines listed on the PDL; the policy did not affect unlisted classes. The PDL group experienced relative increases in medication use of 6.0 30-day fills per person during the year (+11.2%,P<0.001); the increase was more than twice as large for lower-income (+6.6 fills, +12.6%,P<0.001) than higher-income (+3.0 fills, +5.1%,P=0.024) patients.

Conclusion:

Transition to a PDL which covers important classes of medication to manage diabetes and cardiovascular conditions is associated with substantial annual OOP cost savings for patients with diabetes and increased utilization of important classes of medications, especially for lower-income patients.
“Not Alone Anymore”
Authors: Mayer Victoria L. , Siscovick David , Goytia Crispin , Brown Daphne , Hanlen Emily , Flory James , McKee M. Diane , Horowitz Carol R.
Published: May 2020

Background:

New York State Medicaid’s Health Home program is an example of a natural experiment that could affect individuals with diabetes. While evaluations of interventions such as the Health Home program are generally based solely on clinical and administrative data and rarely examine patients’ experience, patients may add to the understanding of the intervention’s implementation and mechanisms of impact.

Objective:

The objective of this study was to qualitatively examine the health and nonmedical challenges faced by Medicaid-insured patients with diabetes and their experiences with the services provided by New York’s Health Homes to address these challenges.

Research Design:

We performed 10 focus groups and 23 individual interviews using a guide developed in collaboration with a stakeholder board. We performed a thematic analysis to identify cross-cutting themes.

Subjects:

A total of 63 Medicaid-insured individuals with diabetes, 31 of whom were enrolled in New York’s Health Home program.

Results:

While participants were not generally familiar with the term “Health Home,” they described and appreciated services consistent with Health Home enrollment delivered by care managers. Services addressed challenges in access to care, especially by facilitating and reminding participants about appointments, and nonmedical needs, such as transportation, housing, and help at home. Participants valued their personal relationships with care managers and the psychosocial support they provided.

Conclusions:

From the perspective of its enrollees, the Health Home program primarily addressed access to care, but also addressed material and psychosocial needs. These findings have implications for Health Home entities and for research assessing their impact.
Using Electronic Health Records in Longitudinal Studies
Authors: Huguet Nathalie , Kaufmann Jorge , O’Malley Jean , Angier Heather , Hoopes Megan , DeVoe Jennifer E. , Marino Miguel
Published: May 2020

Background:

Electronic health records (EHRs) provide rich data on many domains not routinely available in other data, as such, they are a promising source to study changes in health outcomes using longitudinal study designs (eg, cohort studies, natural experiments, etc.). Yet, patient attrition rates in these data are unknown.

Objective:

The objective of this study was to estimate overall and among adults with diabetes or hypertension: (1) patient attrition over a 3-year period at community health centers; and (2) the likelihood that patients with Medicaid permanently switched their source of primary care.

Research Design:

A retrospective cohort study of 2012–2017 data from the Accelerating Data Value Across a National Community Health Center Network (ADVANCE) Clinical Data Research Network of community health centers were used to assess EHR data attrition. Oregon Medicaid enrollment and claims data were used to estimate the likelihood of changing the source of primary care.

Subjects:

A total of 827,657 patients aged 19–64 with ≥1 ambulatory visit from 76 community health center systems across 20 states. In all, 232,891 Oregon Medicaid enrollees (aged 19–64) with a gap of ≥6 months following a claim for a visit billed to a primary care source.

Measures:

Percentage of patients not returning within 3 years of their qualifying visit (attrition). The probability that a patient with Medicaid permanently changed their primary care source.

Results:

Attrition over the 3 years averaged 33.5%; attrition rates were lower (<25%) among patients with diabetes and/or hypertension. Among Medicaid enrollees, the percentage of provider change after a 6-month gap between visits was 12% for community health center patients compared with 39% for single-provider practice patients. Over 3 years, the likelihood of a patient changing to a new provider increased with length of time since their last visit but remained lowest among community health center patients.

Conclusion:

This study demonstrates the use of the EHR dataset is a reliable source of data to support longitudinal studies while highlighting variability in attrition by primary care source and chronic conditions.
Validation of an Automated Early Treatment Diabetic Retinopathy Study Low-contrast Letter Acuity Test
Authors: Pang Yi , Sparschu Lauren , Nylin Elyse , Wang Jingyun
Published: May 2020

SIGNIFICANCE

Automated low-contrast letter acuity (LCLA) has several advantages: consistent luminance, reduced chance of individuals memorizing test letters, and convenient and accurate visual acuity reporting functions. Although automated LCLA might report slightly worse acuity than Sloan LCLA chart, considering its advantages, it may be a viable alternative to Sloan LCLA chart in clinical practice and research.

PURPOSE

The purpose of this study was to determine the repeatability of an automated LCLA measurement and its agreement with the Sloan LCLA chart test in normal participants and reduced-vision participants.

METHODS

Adult participants (n = 49) were measured with both automated Early Treatment Diabetic Retinopathy Study and Sloan LCLA tests, including normal and reduced-vision groups. Low-contrast letter acuity at two contrast levels (2.5 and 10%) was measured at 3 m in a random sequence with both LCLA tests. To test repeatability, participants were retested 1 week later. Repeatability of the two tests between two visits and agreement between automated and Sloan LCLA tests were evaluated using 95% limits of agreement.

RESULTS

In terms of the 95% limits of agreement, the repeatability of both tests was as follows: automated LCLA at 2.5%, ±0.26; automated LCLA at 10%, ±0.22; Sloan LCLA at 2.5%, ±0.23, and Sloan LCLA at 10%, ±0.16. The agreement of the two tests was as follows: ±0.19 at 2.5% and ±0.24 at 10%. The automated LCLA at 2.5 and 10% levels was generally reported one-half to one logMAR line lower than Sloan LCLA (mean differences, −0.04 at 2.5% and −0.13 at 10%; paired t test, P < .05).

CONCLUSIONS

The automated LCLA test shows fairly good test-retest repeatability at both 2.5 and 10% contrast levels. The agreement between the automated and the Sloan low-contrast letter acuity tests was comparable with test-retest agreement. Although the automated LCLA test reports slightly worse acuity than the Sloan LCLA test, it could be an appropriate alternative to the Sloan LCLA test.