bluuebunny/crossref_metadata_2025 huggingface dataset:
SF‐6D utility scores for alcohol use disorder status and alcohol consumption risk levels in the US population
Authors: Barbosa Carolina , Bray Jeremy W. , Dowd William N. , Barnosky Alan , Wittenberg Eve
Published: August 2020

Aims

To estimate US population health utilities for subgroups defined by alcohol use disorder (AUD) status and consumption level.

Design

Cross‐sectional survey.

Setting

Community settings in the United States (i.e. excluding institutional settings).

Participants

A total of 36,042 adults (age 18+) in non‐institutional settings in the United States.

Measurements

We used 12‐item Short Form Survey (SF‐12) data from the National Epidemiologic Survey on Alcohol and Related Conditions–III to calculate mean Short Form–6 dimension (SF‐6D) utility scores across World Health Organization alcohol consumption risk levels—very high risk, high risk, medium risk, low risk and an additional abstinent level—for three groups: (1) the general population (n = 36,042), (2) individuals with life‐time AUD (n = 9925) and (3) individuals with current AUD (n = 5083), and assessed minimally important differences (MIDs) between consumption levels. Each group is a subset of the previous group.

Findings

The general population's mean SF‐6D utility was higher than that of individuals with life‐time or current AUD across all consumption risk levels (0.79 versus 0.76 for both AUD groups). For all groups, SF‐6D utilities increased as consumption risk level decreased to non‐abstinent levels, and reducing consumption from very high risk to any lower level was associated with a statistically significant and meaningful improvement in utility. For individuals with life‐time or current AUD, becoming abstinent from high‐, medium‐ and low‐risk levels was associated with significantly and meaningfully worse utilities.

Conclusions

Higher alcohol consumption risk levels appear to be associated with lower health index scores for the general population and individuals with a history of alcohol use disorder, meaning that higher alcohol consumption is associated with worse health‐related quality of life.
Typologies of illicit drug use in mid‐adulthood: a quasi‐longitudinal latent class analysis in a community‐based sample of twins
Authors: Dash Genevieve F. , Martin Nicholas G. , Agrawal Arpana , Lynskey Michael T. , Slutske Wendy S.
Published: August 2020

Aims

To identify drug use typologies based on substances used and persistence of use over two time points, use a genetically informed design to explore twin concordance of and genetic influence on the use typologies and compare patterns of declined/discontinued (“desistant”) and persistent drug use on drug use correlates.

Design

Latent class analysis was applied to data from a cross‐sectional self‐report survey on current and past drug use. Use characteristics, use disorder, and psychiatric problems were compared across classes.

Setting

Computer‐assisted telephone interview in respondents' homes.

Participants

A total of 3785 individual twins and siblings (1365 men, 2420 women; Mage = 32) from the Australian Twin Registry Cohort III.

Measurements

A comprehensive interview assessed prior to past year and past year use of cannabis, stimulants, cocaine/crack, hallucinogens, opioids, sedatives, inhalants, dissociatives, and solvents; age of first use; opportunity to use; peer drug use; attention deficit/hyperactivity, conduct, antisocial personality, depressive, and substance use disorders; and suicidality.

Findings

A five‐class solution emerged: no/low use (50%), desistant cannabis use (23%), desistant party drug use (18%), persistent prescription drug misuse (4%), and persistent polydrug use (5%). Twin concordances were higher among monozygotic (k = 0.30–0.35) than dizygotic pairs (same‐sex k = 0.19–0.20; opposite sex k = 0.07), and biometric modeling suggested that the persistent polydrug use class, in particular, was highly heritable (a2 = 0.94). Conduct disorder (OR = 2.40), antisocial personality disorder (OR = 3.27), and suicidal ideation (OR = 1.98) increased persistent polydrug use risk; depression (OR = 2.38) and lifetime suicide attempt (OR = 2.31) increased persistent prescription misuse risk. Relative to persistent prescription drug misuse, persistent polydrug use was associated with higher rates of cannabis and stimulant use disorder (OR = 6.14–28.01), younger first substance use (OR = 0.82–0.83), more drug use opportunity (OR = 10.66–66.06), and more drug‐using peers (OR = 4.66–9.20).

Conclusions

Unique patterns of declined/discontinued (“desistant”) and persistent drug use are differentially heritable and differentially associated with risk factors, psychiatric symptoms, and substance use disorder outcomes.
User pathways of e‐cigarette use to support long term tobacco smoking relapse prevention: a qualitative analysis
Authors: Notley Caitlin , Ward Emma , Dawkins Lynne , Holland Richard
Published: August 2020

Background and aims

E‐cigarettes are the most popular consumer choice for support with smoking cessation in the United Kingdom. However, there are concerns that long‐term e‐cigarette use may sustain concurrent tobacco smoking or lead to relapse to smoking in ex‐smokers. We aimed to explore vaping trajectories, establishing e‐cigarette users' perspectives on continued e‐cigarette use in relation to smoking relapse or abstinence.

Design

Qualitative longitudinal study collecting detailed subjective data at baseline and ~12 months later.

Setting

United Kingdom.

Participants

E‐cigarette users (n = 37) who self‐reported that they had used e‐cigarettes to stop smoking at baseline.

Measurements

Semi‐structured qualitative interviews (face‐to‐face or telephone) collected self‐reported patterns of e‐cigarette use. Thematic analysis of transcripts and a mapping approach of individual pathways enabled exploration of self‐reported experiences, motives, resources, and environmental and social influences on vaping and any concurrent tobacco smoking.

Findings

Three broad participant pathways were identified: ‘maintainer’ (e‐cigarette use and not smoking), ‘abstainer’ (neither smoking nor using e‐cigarettes), and ‘relapser’ (dual‐using, or relapsed back to tobacco smoking only). In each pathway, individual experiences with vaping nicotine appeared to play an important role and appeared to be related to psychological and social factors. A social context supportive of vaping was important for the maintainers, as was a belief in the need to overcome nicotine addiction for the abstainers, and dislike of the ‘vaping culture’ expressed by some in the relapser group. Dual‐users held beliefs such as a need for cigarettes at time of acute stress that affirmed dependence on tobacco.

Conclusions

In a sample of UK e‐cigarette users who report having used e‐cigarettes to quit smoking, a social context that supports continued vaping was perceived to be helpful in preventing relapse to smoking.
Psychosocial interventions for reducing alcohol consumption in sub‐Saharan African settings: a systematic review and meta‐analysis
Authors: Sileo Katelyn M. , Miller Amanda P. , Wagman Jennifer A. , Kiene Susan M.
Published: August 2020

Background

Harmful alcohol use is a leading cause of morbidity and mortality in sub‐Saharan Africa (sSA); however, the effects of non‐pharmacological alcohol interventions in this region are unknown.

Design

A systematic review and meta‐analysis of the available literature through 14 March 2019 was undertaken. Two authors extracted and reconciled relevant data and assessed risk of bias. Meta‐analyses were conducted. The review protocol is registered on International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019094509).

Setting

Studies conducted in sSA were eligible for inclusion.

Participants

Individuals participating in interventions aimed at reducing alcohol use.

Interventions

Randomized and non‐randomized controlled trials testing non‐pharmacological interventions (psychosocial and structural) on alcohol consumption in sSA.

Measurements

Eligible outcomes included the Alcohol Use Disorders Identification Test (AUDIT) scores; alcohol abstinence; measures of drinking quantity and frequency; and biomarkers of alcohol consumption.

Findings

Nineteen intervention trials (18 reports) testing psychosocial interventions (no structural interventions included), judged of moderate quality, were included in meta‐analyses. A beneficial effect was identified for psychosocial interventions on alcohol abstinence at 3–6 months [odds ratio (OR) = 2.05, 95% confidence interval (CI) = 1.20–3.48, k = 5, n = 2312, I2 = 79%] and 12–60 months (OR = 1.91, 95% CI = 1.40–2.61, k = 6, n = 2737, I2 = 63%) follow‐up. There were no statistically significant effects found for AUDIT score [2–3 months: mean differences (MD) = −1.13, 95% CI = −2.60 to 0.34, k = 6, n = 992, I2 = 85%; 6 months: MD = −0.83, 95% CI = −1.92 to 0.26, k = 6, n = 1081, I2 = 69%; 12 months: MD = −0.15, 95% CI = −1.66 to 1.36, k = 4; n = 677; I2 = 75%], drinks per drinking day (3 months: MD = –0.22, 95% CI = −2.51 to 2.07, k = 2, n = 359, I2 = 82%; 6–36 months: MD = −0.09, 95% CI = −0.49 to 0.30, k = 3, n = 1450, I2 = 60%) or percentage of drinking days (3 months: MD = −4.60, 95% = −21.14 to 11.94; k = 2; n = 361; I2 = 90%; 6–9 months: MD = 1.96, 95% CI = −6.54 to 10.46; k = 2; n = 818; I2 = 88%).

Conclusion

Psychosocial interventions show promise at increasing self‐reported alcohol abstinence in sSA, but clinical, methodological and statistical heterogeneity across meta‐analytical outcomes suggests that results should be interpreted with caution.
Structural remodelling of the heart valves extracellular matrix during embryo development
Authors: Falla Zuñiga Luis Felipe , Muñoz Cerón Yhoiss Smiht , Salazar Liliana
Published: August 2020

Alterations in heart valve development represent more than 20% of congenital cardiovascular malformations. Most of the functional properties of heart valves depend on extracellular matrix. Despite its relevance, little is known about fibrillar components on developing stages. Our objective is to define histological changes on valves fibrillar components in late embryonic development of Mus musculus. We found type III collagen as the predominant fibre type in the ECM in prenatal stages followed by a switch to a type I predominance for postnatal ages. The change in fibrillar components is necessary to support the normal mechanical function of adult heart valves.
How Does Straw Burning Affect Urban Air Quality in China?
Authors: Guo Shiqi
Published: August 2020

Over the past decade, straw burning has been debated as one of the causes of severe air pollution in developing countries. However, the magnitude and pattern of its impact on air quality have not been precisely estimated. This study employs remote sensing data on straw fires from different satellite sources and examines its overall impact on urban air quality in China. Exploiting daily variations in straw burning activities and air pollution with a difference‐in‐differences strategy across 290 cities and 620 days, I find a clear temporal pattern for the straw burning effect. On the first day after burning, the index of air pollution increases by 6.5 in urban areas, equivalent to 9.4% of the mean. This impact decreases over time and remains significant for at least eight days. The effect is larger for fires located in the upwind direction relative to urban areas and is limited with lower wind speed. In terms of distance, pollution is mostly driven by straw fires within 100 km from urban centers but could also be influenced by fires as far as 600 km away. Among different pollutants, particulate matters are increased most by straw fires. The effect is largest and most persistent in October and November, when straw burning prevails in the north after harvest, but is also non‐negligible in other seasons.
Does thyroid autoimmunity affect the reproductive outcome in women with thyroid autoimmunity undergoing assisted reproductive technology?
Authors: He Qiaohua , Zhang Yujing , Qiu Wenyi , Fan Jingjing , Zhang Cuilian , Kwak‐Kim Joanne
Published: August 2020

Problem

Our study aims to investigate whether the anti‐thyroperoxidase antibody (TPO‐Ab) and TSH level in euthyroid women have any association with reproductive outcomes after the ART cycle.

Methods of study

A total of 1107 patients who were enrolled in the study were divided into four groups based on serum TSH level and TPO‐Ab status: group A, 0.3 ≤ TSH < 2.5 mIU/L and TPO‐Ab−; group B, 0.3 ≤ TSH < 2.5 mIU/L and TPO‐Ab+; group C, 2.5 ≤ TSH < 4.2 mIU/L, and TPO‐Ab−; and group D, 2.5 ≤ TSH < 4.2 mIU/L, TPO‐Ab+. The differences in ART cycles and pregnancy outcomes were analyzed between study groups.

Results

The fertilization rate in group D (73%) was significantly lower than that in groups A (83% P < .001), B (84% P = .001), and C (82% P = .002). The biochemical pregnancy rates of groups B (7%) and D (12%) were significantly higher than those of group A (2%) (P = .028 and P = .017, respectively). TPO‐Ab was related to a higher biochemical pregnancy rate (P = .002, OR = 5.311, 95% CI 1.859‐15.169) and TSH over 2.5 mIU/L was related to higher ICSI rate (P = .001, OR = 1.759, 95% CI 1.250‐2.476) by logistic regression analysis. The receiver operating characteristic (ROC) also verified the results.

Conclusion

The impacts of TSH ≥ 2.5 mIU/L on the intracytoplasmic sperm injection (ICSI) rate, TSH ≥ 2.5 mIU/L and TPO‐Ab+ on the fertilization rate, and TPO‐Ab+ on the biochemical pregnancy rate, rather than the effect on abortion, clinical pregnancy, and live birth, were emphasized.
Are different markers of endometrial receptivity telling us different things about endometrial function?
Authors: Hviid Saxtorph Malene , Persson Gry , Hallager Trine , Birch Petersen Kathrine , Eriksen Jens O. , Larsen Lise Grupe , Macklon Nick , Hviid Thomas Vauvert F.
Published: August 2020

Problem

To what extent do endocrine, immunological, gene expression and histological markers of endometrial receptivity correlate?

Method of study

Between November 2017 and September 2019, 121 women referred to a University Hospitals Fertility Clinic consented to inclusion in this cohort study. The women underwent timed endometrial biopsy followed by blood samples in a hormone‐substituted cycle. Of these, 37 women had just started IVF treatment, and the remaining 84 had experienced recurrent implantation failure following IVF/ICSI. The hormone‐substituted cycle consisted of initiation with oral oestradiol followed by addition of vaginal progesterone treatment for five full days. Endometrial biopsies were subject to histological examination, immune cell markers by immunohistochemistry (CD56+, CD16+, CD163+, FoxP3) and gene expression microarray analyses with the endometrial receptivity array (ERA®) test (Igenomix). Plasma progesterone and oestradiol were measured on the day of biopsy.

Results

CD56+uterine natural killer (uNK) cell counts correlate with transcriptional markers of endometrial receptivity assessed by the ERA test. Endometrial maturation, receptivity and immunological markers were not correlated with mid‐luteal blood plasma progesterone level. Mid‐luteal serum oestradiol level correlated with markers of endometrial maturation and receptivity. The tests were carried out during a standard hormone substitution cycle, and the findings may not apply in the natural cycle.

Conclusion

CD56+uNK cell counts and endometrial receptivity assessed by the ERA test appear to be linked. Mid‐luteal progesterone levels were not correlated to the tested markers of endometrial receptivity. In contrast, mid‐luteal oestradiol level was inversely related to markers of endometrial receptivity and maturation.
Human chorionic gonadotropin‐mediated modulation of pregnancy‐compatible peripheral blood natural killer cells in frozen embryo transfer cycles
Authors: Huber Warren J. , Sauerbrun‐Cutler May‐Tal , Krueger Paula M. , Lambert‐Messerlian Geralyn , Sharma Surendra
Published: August 2020

Problem

To evaluate pregnancy‐compatible phenotypic and functional changes in peripheral blood natural killer (pNK) cells during frozen embryo transfer (FET) cycles.

Method of study

Peripheral blood was collected from patients undergoing frozen embryo transfer cycles at three separate time points in the cycle. pNK cell phenotype was analyzed by flow cytometry. Impact of pregnancy status on pNK cell cytotoxicity was characterized by two methods: (1) a three‐dimensional endovascular tube formation approach and (2) a NK cell‐specific K562 cell kill assay.

Results

A total of 35 patients were enrolled, 15 with clinical pregnancies and 20 with negative serum β‐hCG levels. Overall percentage of CD45+CD3−CD56+ pNK cell did not change during the FET cycle. Pregnancy resulted in an increase in CD45+CD3−CD56+ pNK cell population on the day of serum β‐hCG. pNK cells from non‐pregnant patients caused significant tube disruption when compared to pregnant patients. Addition of serum from pregnant women reduced the tube disruption by pNK cells from non‐pregnant patients. pNK cells from pregnant patients showed significantly lower cytotoxicity toward K562 cells in serum‐free conditions. The addition of pregnancy serum decreased non‐pregnant pNK cell cytotoxicity. Pregnancy status had no impact on VEGF‐A and VEGF‐C serum levels. Recombinant hCG added to non‐pregnant serum resulted in a significant reduction in non‐pregnant pNK cell‐mediated K562 cell kill.

Conclusion

There was no difference in pNK cell populations based on timing of the FET cycle. However, pregnancy increased the percentage of CD45+CD3−CD56+ pNK cells. Additionally, pNK cells from pregnant women have reduced cytotoxicity and this is possibly mediated by hCG.
The effect of an ultrasound‐activated needle tip tracker needle on the performance of sciatic nerve block on a soft embalmed Thiel cadaver
Authors: McKendrick M. , Sadler A. , Taylor A. , Seeley J. , Filipescu T. , Mustafa A. , McKendrick G. , Halcrow J. , Raju P. , McLeod G. A.
Published: August 2020

In this study, we measured the performance of medical students and anaesthetists using a new tracker needle during simulated sciatic nerve block on soft embalmed cadavers. The tracker needle incorporates a piezo element near its tip that generates an electrical signal in response to insonation. A circle, superimposed on the ultrasound image surrounding the needle tip, changes size and colour according to the position of the piezo element within the ultrasound beam. Our primary objective was to compare sciatic block performance with the tracker switched on and off. Our secondary objectives were to record psychometrics, procedure efficiency, participant self‐regulation and focused attention using eye‐tracking technology. Our primary outcome measures were the number of steps successfully performed and the number of errors committed during each block. Videos were scored by trained experts using validated checklists. Sequential tracker activation and deactivation was randomised equally within subjects. With needle activation, steps improved in 10 (25%) subjects and errors reduced in six (15%) subjects. The most important steps were: needle tip identification before injection, OR (95%CI) 2.12 (1.61–2.80; p < 0.001); and needle tip identification before advance of the needle, 1.80 (1.36–2.39; p < 0.001). The most important errors were: failure to identify the needle tip before injection, 2.40 (1.78–3.24; p < 0.001); and failure to quickly regain needle tip position when tip visibility was lost, 2.03 (1.5–2.75; p < 0.001). In conclusion, needle‐tracking technology improved performance in a quarter of subjects.
Lean HRM practices in work integration social enterprises: Moving towards social lean production. Evidence from Italian case studies*
Authors: Signoretti Andrea , Sacchetti Silvia
Published: August 2020

Lean production human resource management (HRM) practices, which are deemed to increase firms’ competitiveness through a skilled and empowered workforce, have arisen in the context of for‐profit companies. The same attention to lean HRM practices has not been paid in non‐profit organizations. In turn, few studies have looked into the adoption of for‐profit HRM practices within such organizations or focused on single practices and ordinary workers. Within this research, dichotomous positions between advocates and opponents have emerged, but with an underlying universalistic perspective considering HRM practices as detached from context. We consider HRM practices as context dependent and conduct a new study concerning lean production HRM practices in work integration social enterprises (WISEs), a particular type of NPO and social enterprise that focuses on building employability and jobs for vulnerable workers. We rely on three case studies involving multiple actors. Our exploratory results suggest that WISEs realize social lean production. They implement lean HRM practices by adapting them to their specific context and integrating both social and economic goals.
Letter: immunotherapy in IBD patients in a SARS‐CoV‐2 endemic area
Authors: Waggershauser Constanze H. , Tillack‐Schreiber Cornelia , Berchtold‐Benchieb Christine , Szokodi Daniel , Howaldt Stefanie , Ochsenkühn Thomas
Published: August 2020

LINKED CONTENT

This article is linked to Taxonera et al papers. To view these articles, visit https://doi.org/10.1111/apt.15804 and https://doi.org/10.1111/apt.15955
Editorial – out with the old and in with the new? Gastrointestinal bleeding risk of P2Y12 inhibitors following acute coronary syndrome
Authors: McFarlane Michael , Disney Benjamin R.
Published: August 2020

LINKED CONTENT

This article is linked to Abraham et al paper. To view this article, visit https://doi.org/10.1111/apt.15790
Letter: improve survival! Place early pre‐emptive TIPSS in high‐risk variceal bleeders
Authors: García‐Pagán Juan Carlos , Bosch Jaume , Trebicka Jonel , Abraldes Juan G , Albillos Agustín , Grønbæk Henning , Giráldez Álvaro , Zipprich Alexander , Bureau Christophe , Hernández‐Gea Virginia ,   the International Variceal Bleeding Observational Study Group, Baveno Cooperation
Published: August 2020

LINKED CONTENT

This article is linked to Dunne et al papers. To view these articles, visit https://doi.org/10.1111/apt.15797 and https://doi.org/10.1111/apt.15953
Editorial: treating hepatorenal syndrome—a window and the views
Authors: Palaniyappan Naaventhan , Aithal Guruprasad Padur
Published: August 2020

LINKED CONTENT

This article is linked to Moore et al and Allegretti et al papers. To view these articles, visit https://doi.org/10.1111/apt.15836 and https://doi.org/10.1111/apt.15981
Letter: does Helicobacter pylori infection limit the health effects of the Mediterranean diet?
Authors: Vermorken Alphons J.M. , Zhu Jingjing , Cui Yali
Published: August 2020

LINKED CONTENT

This article is linked to Rajilic‐Stojanovic et al paper. To view this article, visit https://doi.org/10.1111/apt.15650
Letter: prevalence and patterns of gastrointestinal symptoms in a large Western cohort of patients with COVID‐19
Authors: Ianiro Gianluca , Porcari Serena , Settanni Carlo Romano , Bibbò Stefano , Ponziani Francesca Romana , Zileri dal Verme Lorenzo , Franceschi Francesco , Cammarota Giovanni , Gasbarrini Antonio ,   Gemelli against COVID‐19 Working Group
Published: August 2020

LINKED CONTENT

This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15986
Letter: online search trends suggest patient concerns around immunosuppression use in inflammatory bowel disease during COVID‐19 in the United Kingdom
Authors: Quraishi Mohammed Nabil , Segal Jonathan P. , Cooney Rachel , Kennedy Nicholas A. , Ainley Rachel , Sharma Naveen , Bhala Neeraj B. , Brookes Matthew J.
Published: August 2020

LINKED CONTENT

This article is linked to Taxonera et al paper. To view this article, visit https://doi.org/10.1111/apt.15804
Letter: sequential or combinated systemic treatment for unresectable hepatocellular carcinoma
Authors: Mo Dun‐Chang , Luo Peng‐Hui , Huang Jian‐Feng
Published: August 2020

LINKED CONTENT

This article is linked to Kirstein et al papers. To view these articles, visit https://doi.org/10.1111/apt.15789 and https://doi.org/10.1111/apt.15980
Letter: immunotherapy for IBD patients in a SARS‐CoV‐2 endemic area—authors' reply
Authors: Taxonera Carlos , Sagastagoitia Iñigo , Alba Cristina
Published: August 2020

LINKED CONTENT

This article is linked to Taxonera et al and Szokodi papers. To view these articles, visit https://doi.org/10.1111/apt.15804 and https://doi.org/10.1111/apt.15897
Editorial: tenofovir disoproxil fumarate vs entecavir in patients with chronic hepatitis B and renal impairment—still an open issue
Authors: Lee Sung Won , Kim Seung Up
Published: August 2020

LINKED CONTENT

This article is linked to Lampertico et al paper. To view this article, visit https://doi.org/10.1111/apt.15901
Editorial: serum HBV RNA biphasic decline in patients with HBeAg‐positive chronic hepatitis B treated with nucleos(t)ide analogues
Authors: Ding Yang , Dou Xiaoguang
Published: August 2020

LINKED CONTENT

This article is linked to Liu et al papers. To view these articles, visit https://doi.org/10.1111/apt.15890 and https://doi.org/10.1111/apt.15993
Editorial: pregnancy and the gastroenterologist
Authors: Leung Kristel K. , Huang Vivian
Published: August 2020

LINKED CONTENT

This article is linked to Faulkes et al paper. To view this article, visit https://doi.org/10.1111/apt.15908
Editorial: comorbidities in patients with chronic hepatitis B—authors' reply
Authors: Yoon Eileen L. , Oh Hyunwoo , Jun Dae Won , Nguyen Mindie H.
Published: August 2020

LINKED CONTENT

This article is linked to Oh et al and Liang et al papers. To view these articles, visit https://doi.org/10.1111/apt.15867 and https://doi.org/10.1111/apt.15938
Letter: prevalence and patterns of gastrointestinal symptoms in a large Western cohort of patients with coronavirus disease 2019—authors' reply
Authors: Tian Yuan , Rong Long
Published: August 2020

LINKED CONTENT

This article is linked to Tian et al and Ianiro et al papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15946
Editorial: serum HBV RNA biphasic decline in patients with HBeAg‐positive chronic hepatitis B treated with nucleos(t)ide analogues—authors' reply
Authors: Liu Shi , Li Wanying , Sun Jian
Published: August 2020

LINKED CONTENT

This article is linked to Liu et al and Ding and Dou papers. To view these articles, visit https://doi.org/10.1111/apt.15890 and https://doi.org/10.1111/apt.15975
Letter: recognising frailty in patients with inflammatory bowel disease is crucial for appropriate personalised treatment
Authors: Lovatt Jessica , Selinger Christian P.
Published: August 2020

LINKED CONTENT

This article is linked to Kochar et al paper. To view this article, visit https://doi.org/10.1111/apt.15821
Letter: monitoring interval for thiopurine therapy – a comment
Authors: Desai Devendra , Abraham Philip
Published: August 2020

LINKED CONTENT

This article is linked to Kreijne et al paper. To view this article, visit https://doi.org/10.1111/apt.15734
Review article: experimental therapies in autoimmune hepatitis
Authors: Halliday Neil , Dyson Jessica Katharine , Thorburn Douglas , Lohse Ansgar W. , Heneghan Michael A.
Published: August 2020

Background

Current therapeutic options for autoimmune hepatitis (AIH) are limited by adverse events associated with corticosteroids and thiopurines and the limited evidence base for second‐ and third‐line treatment options. Furthermore, current treatment approaches require long‐term exposure of patients to pharmacological agents. There have been significant advances in the understanding of the mechanisms underpinning autoimmunity and an expansion in the available therapeutic agents for suppressing autoimmune responses or potentially restoring self‐tolerance.

Aim

To review the mechanisms and evidence for experimental therapies that are being actively explored in the management of AIH.

Methods

We have reviewed the literature relating to a range of novel therapeutic immunomodulatory treatment strategies and drugs.

Results

Drugs which block B cell‐activating factor of the tumour necrosis factor family (BAFF) and tumour necrosis factor α are currently in clinical trials for the treatment of AIH. Experimental therapies and technologies to increase immune tolerance, such as pre‐implantation factor and regulatory T cell therapies, are undergoing development for application in autoimmune disorders. There is also evidence for targeting inflammatory pathways to control other autoimmune conditions, such as blockade of IL1 and IL6 and Janus‐associated kinase (JAK) inhibitors.

Conclusions

With the range of tools available to clinicians and patients increasing, it is likely that the therapeutic landscape of AIH will change over the coming years and treatment approaches offering lower corticosteroid use and aiming to restore immune self‐tolerance should be sought.
Thiopurines vs methotrexate: Comparing tolerability and discontinuation rates in the treatment of inflammatory bowel disease
Authors: Vasudevan Abhinav , Parthasarathy Nina , Con Danny , Nicolaides Steven , Apostolov Ross , Chauhan Ayushi , Bishara Maria , Luber Raphael P. , Joshi Neetima , Wan Anna , Rickard James A. , Long Tony , Connoley Declan , Sparrow Miles P. , Gibson Peter R. , van Langenberg Daniel R.
Published: August 2020

Background

There are safety concerns regarding immunomodulators (thiopurines and methotrexate) for treatment of inflammatory bowel disease (IBD).

Aim

To compare the long‐term tolerability, and persistence of thiopurine and methotrexate therapy in IBD.

Methods

A retrospective cohort study was performed at two hospitals between 1 January 2004 and 31 December 2016 for patients commenced on thiopurines or methotrexate for IBD. Treatment discontinuation rates, intolerances and disease activity were obtained from medical records.

Results

There were 782 patients commenced on immunomodulator therapy; 244 (31%) on methotrexate with folate (67% subcutaneous therapy) and 538 (69%) on thiopurine (73% azathioprine). Median follow‐up was 42 vs 47 months (P = 0.09). In patients on thiopurines, median 6‐TGN was 298 pmol/8 x 108 RBCs, while the median dose of methotrexate was 25 mg weekly. Methotrexate recipients had a higher rate of prior immunomodulator intolerance, were typically older and had a longer disease duration (54% vs 3%, median 43 vs 36 years, 6 vs 5 years, respectively, each P < 0.05). Overall, 208 (27%) discontinued therapy due to adverse events, (40% on methotrexate vs 19% on thiopurines, P < 0.001), including nausea (18% vs 4%), fatigue (7% vs 2%) and hepatotoxicity (8% vs 2%, each P < 0.001). Hospitalisations from adverse events (0.8% vs 0.9%) and serious infections (9% vs 12%), and deaths (1% vs 0%) were comparable between groups (all P > 0.05). Discontinuation due to adverse events occurred later in patients on methotrexate than on thiopurines (median 7 vs 5 months, P = 0.08).

Conclusion

Discontinuation of methotrexate occurred at rates twice that of dose‐optimised thiopurine therapy.
Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome?
Authors: Andersen Freja Drost , Simonsen Ulf , Andersen Charlotte Uggerhøj
Published: August 2020

Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha‐adrenoceptors, muscarinic and histamine receptors, human ether‐a‐go‐go‐channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine.
Steady‐state pharmacokinetic and pharmacodynamic profiling of colistin in critically ill patients with multi‐drug–resistant gram‐negative bacterial infections, along with differences in clinical, microbiological and safety outcome
Authors: Ram Kishna , Sheikh Salim , Bhati Rahul Kumar , Tripathi Chakra Dhar , Suri Jagdish Chander , Meshram Girish Gulab
Published: August 2020

Limited data are present regarding the steady‐state pharmacokinetics and pharmacodynamics of colistin in critically ill patients suffering from multi‐drug–resistant gram‐negative bacterial (MDR‐GNB) infections. We aimed to profile the steady‐state pharmacokinetics and pharmacodynamics of colistin in critically ill patients with MDR‐GNB infections, along with determining the predictors that could influence the clinical, microbiological and safety outcome. We recruited 30 critically ill patients suffering from MDR‐GNB infections in our prospective open‐label study. Intravenous colistimethate sodium (CMS) 2 million IU was administered concurrently with inhalational CMS 1 million IU every 8 hours. Steady‐state plasma colistin levels were measured. Logistic regression analysis was used to identify various predictors of clinical, microbiological and safety outcome. A large variability was observed in the steady‐state colistin pharmacokinetic/pharmacodynamic parameters, along with the factors that influenced the clinical, microbiological and safety outcome. In conclusion, steady‐state colistin pharmacokinetic and pharmacodynamic parameters observed in our study were largely consistent with those reported in previous studies. High acute physiology and chronic health evaluation II scores were associated with poor clinical outcome. Log‐transformed colistin maximum concentration, area under the plasma concentration curve for 8 hours, apparent total body clearance and apparent volume of distribution were significantly associated with the safety outcome.
Nonparametric trend estimation in functional time series with application to annual mortality rates
Authors: Martínez‐Hernández Israel , Genton Marc G.
Published: August 2020

We address the problem of trend estimation for functional time series. Existing contributions either deal with detecting a functional trend or assuming a simple model. They consider neither the estimation of a general functional trend nor the analysis of functional time series with a functional trend component. Similarly to univariate time series, we propose an alternative methodology to analyze functional time series, taking into account a functional trend component. We propose to estimate the functional trend by using a tensor product surface that is easy to implement, to interpret, and allows to control the smoothness properties of the estimator. Through a Monte Carlo study, we simulate different scenarios of functional processes to show that our estimator accurately identifies the functional trend component. We also show that the dependency structure of the estimated stationary time series component is not significantly affected by the error approximation of the functional trend component. We apply our methodology to annual mortality rates in France.
Medullary tyrosine hydroxylase catecholaminergic neuronal populations in sudden unexpected death in epilepsy
Authors: Patodia Smriti , Tan Ian , Ellis Matthew , Somani Alyma , Scheffer Ingrid E. , Sisodiya Sanjay M. , Thom Maria
Published: August 2020

Sudden unexpected death in epilepsy (SUDEP) is mechanistically complex and one probable cause is seizure‐related respiratory dysfunction. Medullary respiratory regulatory nuclei include the pre‐Bötzinger complex (pre‐BötC) in the ventrolateral medulla (VLM), the medullary raphé nuclei (MR) and nucleus of solitary tract in the dorsomedial medulla (DMM). The region of the VLM also contains intermingled tyrosine hydroxylase (TH) catecholaminergic neurones which directly project to the pre‐BötC and regulate breathing under hypoxic conditions and our aim was to evaluate these neurones in SUDEP cases. In post‐mortem cases from three groups [SUDEP (18), epilepsy controls (8) and non‐epilepsy controls (16)] serial sections of medulla (obex + 2 to + 13 mm) were immunolabeled for TH. Three regions of interest (ROI) were outlined (VLM, DMM and MR) and TH‐immunoreactive (TH‐IR) neurones were evaluated using automated detection for overall labeling index (neurones and processes) and neuronal densities and compared between groups and relative to obex level. C‐fos immunoreactivity was also semi‐quantitatively evaluated in these regions. We found no significant difference in the density of TH‐IR neurones or labeling index between the groups in all regions. Significantly more TH‐IR neurones were present in the DMM region than VLM in non‐epilepsy cases only (P < 0.01). Regional variations in TH‐IR neurones with obex level were seen in all groups except SUDEP. We also identified occasional TH neurones in the MR region in all groups. There was significantly less c‐fos labeling in the VLM and MR in SUDEP than non‐epilepsy controls but no difference with epilepsy controls. In conclusion, in this series we found no evidence for alteration of total medullary TH‐IR neuronal numbers in SUDEP but noted some differences in their relative distribution in the medulla and c‐fos neurones compared to control groups which may be relevant to the mechanism of death.
The importance of trace element analyses in detrital Cr‐spinel provenance studies: An example from the Upper Triassic of the Barents Shelf
Authors: Harstad Trond Svånå , Mørk E. Mai Britt , Slagstad Trond
Published: August 2020

Investigations of sandstone provenance often involve U–Pb dating and chemical/mineralogical investigations of detrital minerals that are stable in sediments. As most stable detrital minerals are from felsic–intermediate rocks, investigations of the only mafic–ultramafic mineral considered stable in sediments, chromian spinel (Cr‐spinel), can reveal contributions from mafic–ultramafic sources. Cr‐spinel chemical compositions are tied to petrogenesis, making it possible to identify the nature of, and differentiate between, potential sources. Earlier detrital Cr‐spinel studies have focused on major and minor element compositions, however, the advent of laser‐ablation analytical techniques now allow routine mineral trace element analyses. Here, we integrate major, minor and trace element compositions of detrital Cr‐spinel from sandstones with a well‐characterised provenance from the Triassic (Anisian to Early Norian) Snadd and De Geerdalen formations of the Barents Shelf. The analysed Cr‐spinel compositions are depleted in the major element cations Fe3+, Al and Mg and enriched in Cr and Fe2+. Relative to MORB chromite, the minor and trace element data show high concentrations of Zn, Co and Mn, low concentrations of Ni and Ga and variable concentrations of Ti, V and Sc. The major element compositions of the detrital Cr‐spinel are similar to ophiolite‐associated Cr‐spinel, while the trace element compositions indicate a more complex petrogenesis influenced by metamorphic alteration. The compositional variations between sample locations are small, suggesting similar source rocks for the detrital Cr‐spinel throughout the study area. The most likely sources of the Cr‐spinel grains are metamorphosed ophiolite complexes in the Uralian Orogen, in accordance with earlier provenance studies. The novel addition of trace element compositions to detrital Cr‐spinel studies adds significant source‐sensitive information.
Lipid accumulation in macrophages confers protumorigenic polarization and immunity in gastric cancer
Authors: Luo Qin , Zheng Naisheng , Jiang Li , Wang Tingting , Zhang Peng , Liu Yi , Zheng Peiming , Wang Weiwei , Xie Guohua , Chen Lei , Li Dongdong , Dong Ping , Yuan Xiangliang , Shen Lisong
Published: August 2020

Heterotypic interactions between tumor cells and macrophages can enable tumor progression and hold potential for the development of therapeutic interventions. However, the communication between tumors and macrophages and its mechanism are poorly understood. Here, we find that tumor‐associated macrophages (TAM) from tumor‐bearing mice have high amounts of lipid as compared to macrophages from tumor‐free mice. TAM also present high lipid content in clinical human gastric cancer patients. Functionally, TAM with high lipid levels are characterized by polarized M2‐like profiling, and exhibit decreased phagocytic potency and upregulated programmed death ligand 1 (PD‐L1) expression, blocking anti–tumor T cell responses to support their immunosuppressive function. Mechanistically, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identifies the specific PI3K pathway enriched within lipid‐laid TAM. Lipid accumulation in TAM is mainly caused by increased uptake of extracellular lipids from tumor cells, which leads to the upregulated expression of gamma isoform of phosphoinositide 3‐kinase (PI3K‐γ) polarizing TAM to M2‐like profiling. Correspondingly, a preclinical gastric cancer model is used to show pharmacological targeting of PI3K‐γ in high‐lipid TAM with a selective inhibitor, IPI549. IPI549 restores the functional activity of macrophages and substantially enhances the phagocytosis activity and promotes cytotoxic‐T‐cell‐mediated tumor regression. Collectively, this symbiotic tumor‐macrophage interplay provides a potential therapeutic target for gastric cancer patients through targeting PI3K‐γ in lipid‐laden TAM.
lncARSR sponges miR‐34a‐5p to promote colorectal cancer invasion and metastasis via hexokinase‐1‐mediated glycolysis
Authors: Li Shuai , Zhu Kongxi , Liu Lan , Gu Jiaoyang , Niu Huanmin , Guo Jianqiang
Published: August 2020

Aerobic glycolysis metabolic reprogramming is one of the most important hallmarks of malignant tumors. Increasing evidence indicates that long non‐coding RNAs (lncRNAs) are able to regulate glycolysis metabolic reprogramming and promote cancer progression by functioning as competing endogenous RNAs. lncARSR is a newly identified onco‐lncRNA in renal cancer, but its potential role in metastatic colorectal cancer (CRC) remains unclear. Here, we analyzed specimens from 89 patients with CRC and demonstrated that lncARSR was highly expressed in CRC tissues and negatively associated with survival. Positron emission tomography‐computed tomography imaging with fluoro‐2‐d‐deoxyglucose F18 to evaluate glucose uptake showed that lncARSR expression was positively correlated with maximum standardized uptake values. Functionally, ectopic expression of lncARSR promoted the invasion, metastasis, and glycolysis metabolic reprogramming of CRC cells in vitro and in vivo, while these activities were inhibited by silencing lncARSR expression. Molecularly, lncARSR sponged miR‐34a‐5p and further mediated hexokinase 1 (HK1)‐related aerobic glycolysis in vitro and in vivo. Clinically, high lncARSR and HK1 expression predicted poor survival of patients with CRC, especially when combined with low miR‐34a‐5p expression. Collectively, we identified lncARSR as an onco‐lncRNA in CRC and demonstrated that the combination of lncARSR/miR‐34a‐5p/HK1 may be a potential prognostic biomarker of CRC.
Maternal Support of Children’s Math Learning in Associations Between Family Income and Math School Readiness
Authors: Lombardi Caitlin M. , Dearing Eric
Published: August 2020

This study examined maternal support of children’s math learning at 36 months (n = 140) as a mediator of the association between early childhood family income and children’s counting and calculation skills at 4½ and 6–7 years. Family income was associated with this measure of children’s math school readiness, but the association was almost entirely indirect and mediated by observed maternal support of children’s numerical skills at 36 months. Maternal support of children’s spatial concept and general learning (cognitive stimulation and sensitivity) were not significant mediators of this association. Results suggest that income‐based gaps in counting and calculation skills at school entry may be due in part to the constraints that low family income places on early numerical learning support.
In vivo confocal microscopy and trachomatous conjunctival scarring: Predictors for clinical progression
Authors: Hoffman Jeremy J. , Massae Patrick , Weiss Helen A. , Makupa William , Burton Matthew J. , Hu Victor H.
Published: August 2020

Importance

In vivo confocal microscopy (IVCM) provides high‐resolution images of the ocular surface and has been validated in trachomatous conjunctival scarring.

Background

This study used IVCM to identify parameters associated with clinical scarring progression.

Design

Prospective cohort study.

Participants

A total of 800 participants in Northern Tanzania with trachomatous scarring.

Methods

Participants underwent clinical examination, photography and IVCM at baseline and 24‐months. Clinical progression of scarring was defined by comparing baseline and 24‐month photographs. Masked grading of IVCM images was used to identify scarring at both time points. Multivariable logistic regression was used to assess factors associated with clinical progression.

Main Outcome Measures

Risk factors associated with clinical scarring progression.

Results

Clinical and IVCM assessment of 800 participants were performed at baseline, with 617 (77.1%) seen at 24‐months. Of these, 438 of 617 (71.0%) had gradable IVCM images at both time points and 342 of 438 (78.1%) of these could be graded as showing definite clinical progression or no progression on image comparison. Clinical progression was found to occur in 79 of 342 (23.1%). After adjusting for age and sex, clinical scarring progression was strongly associated with a high IVCM connective tissue organization score at both baseline (odds ratio [OR] = 1.84 for each increase in scarring category; P = .002) and 24‐months (OR = 1.60; P = .02). Dendritiform cells present at 24‐months were strongly associated with clinical scarring progression after adjustment (OR = 2.62; P = .03).

Conclusions and Relevance

Quantitative IVCM parameters, including connective tissue organization score and the presence of dendritiform cells, are associated with disease progression and may be useful markers in trachoma and other conjunctival fibrotic diseases.
Cutaneous Epstein‐Barr virus‐associated smooth muscle tumor in immunosuppression
Authors: Matin Rubeta N. , Ieremia Eleni
Published: August 2020

A 36‐year‐old renal transplant recipient presented 15 months post‐transplantation with a cutaneous spindle cell neoplasm with features of smooth muscle differentiation treated with local excision. 1.4 years later, a magnetic resonance imaging liver scan with gadolinium demonstrated multiple bilobar enhancing hepatic lesions, in keeping with metastases. A core biopsy revealed morphological appearances similar to the previous cutaneous spindle cell neoplasm. Epstein‐Barr virus early RNA (EBER) in situ hybridization demonstrated strong diffuse staining of both cutaneous and liver tumor cells for EBER indicative of Epstein‐Barr virus (EBV) infection. This is a rare presentation of multifocal EBV‐associated smooth muscle tumors first presenting in the skin in an adult renal transplant recipient, which, despite being multifocal and involving the liver, may confer a better prognosis than predicted.