bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing pre‐ovulatory follicle diameter and weaning‐to‐ovulation interval in spontaneously ovulating sows in tropical environment
Authors: Pearodwong Pachara , Tretipskul Chanyuth , Panyathong Raphee , Tummaruk Padet
Published: October 2020

Follicle development and timing of ovulation are indicators of the reproductive performance of sows. The present study aimed to determine factors influencing pre‐ovulatory follicle diameter and weaning‐to‐ovulation interval (WOI) in spontaneously ovulating sows in tropical climates with special emphasis on breed, parity and backfat thickness at weaning. In total, 80 sows were included in the study. Follicle development was determined by using transrectal real‐time B‐mode ultrasonography every 6 hr after standing oestrus. Weaning‐to‐oestrous interval (WEI), oestrous‐to‐ovulation interval (EOI), WOI and the diameter of graafian follicles were investigated in relation to breed, parity number (1, 2–3 and 4–7) and backfat thickness (low, moderate and high) of sows. Overall, WEI, EOI, WOI and the pre‐ovulatory follicle diameter were 92.5 ± 21.6 hr, 64.3 ± 19.3 hr, 156.3 ± 29.1 hr and 10.3 ± 2.0 mm, respectively. Pre‐ovulatory follicle size was smaller in primiparous sows compared with sows of greater parity, 4–7 (9.7 ± 0.51 and 11.7 ± 0.52 mm, respectively, p < .05). Weaning‐to‐ovulation interval was positively correlated with WEI (r = 0.75, p < .001) and EOI (r = 0.66, p < .001), but negatively correlated with size of the graafian follicle (r = –0.34, p < .01). Sows with a shorter WEI had a larger pre‐ovulatory follicle diameter (at 64 hr after oestrus) (r = –0.37, p < .01). Sows with low backfat thickness had a WOI 23.4 hr longer than those with moderate backfat thickness (p < .05) and 17.6 hr longer than sows with a high backfat thickness (p = .140). The follicle diameter in primiparous sows with high backfat thickness (11.7 ± 1.1 mm) was higher than in those with low (8.9 ± 0.7 mm, p < .05) or moderate (8.6 ± 0.8, p < .05) backfat thickness. In conclusion, factors influencing follicle diameter and WOI in sows included parity number and backfat thickness at weaning. The impact of backfat thickness on follicle diameter, WEI and WOI was most pronounced in primiparous sows.
Probe‐based confocal laser endomicroscopy for pleural malignancies diagnosis
Authors: Bonhomme Olivier , Heinen Vincent , Detrembleur Nancy , Corhay Jean‐Louis , Louis Renaud , Duysinx Bernard
Published: October 2020

Probe based confocal laser endomicroscopy (pCLE) is an optical imaging tool allowing live imaging of tissues at a cellular level. It remains experimental but its clinical value as a diagnostic/guiding tool is apparent. To address the lack of data in thoracic oncology and pleural diseases, we show the ability of pCLE during medical thoracoscopy to distinguish benign from malignant pleural involvement.

See related Editorial
Characterization of the novel HLA‐B*15:474 allele by next‐generation sequencing
Authors: Genebrier Steve , Elsermans Vincent , Texeraud Emeric , Bertrand Gerald , Renac Virginie
Published: October 2020

B*15:474 differs from B*15:01:01:01 by one nucleotide substitution at position 923 in exon 5.
Current research: effect of time restricted eating on weight and cardiometabolic health
Authors: Gabel Kelsey , Varady Krista A.
Published: October 2020

Intermittent fasting has grown in popularity as a weight loss strategy in recent years. In particular, time restricted eating (TRE) has been popularized in the diet industry with dozens of books touting its ability to promote weight loss and improve glucose regulation. TRE involves confining the eating window to a specified number of hours per day (usually 4–10 h), and fasting (with zero‐calorie beverages) for the remaining hours of the day. While several studies of TRE have been performed in rodent models, human studies are only now emerging. The goal of this review is to summarize the effects of TRE on body weight and cardiometabolic disease risk factors in human subjects. Accumulating evidence shows that TRE may spontaneously decrease energy intake by 20–30% under ad libitum conditions, producing small but statistically significant weight loss of 1–4%. In addition, TRE may significantly decrease systolic and diastolic blood pressure independent of weight loss. Further, improvements in fasting insulin and insulin resistance have also been reported. Taken together, these preliminary data suggest that TRE produces mild weight loss, and also may improve some aspects of cardiometabolic health by lowering blood pressure and insulin resistance.

image
Structural Characterization of Rocks Using the X-ray Microtomography Technique
Authors: Lima Lithiely Melo de , Soares José Agnelo
Published: October 2020

In this article are presented the results obtained for the determination of mineral composition and petrophysical properties of eight sedimentary rock samples through a proposed new method, which is supported by X-ray microtomography image analysis (microCT). The results are compared with their corresponding ones obtained by traditional techniques in order to assess the efficiency of the new method. Three samples of carbonate rocks and five of sandstone were used in this study. Two sandstone samples come from the Rio do Peixe basin (BRP, at northeastern Brazil) while the rest were extracted from USA basins. The best results were obtained in the quantification of the mineral composition of the rocks and, consequently, in the estimation of grain density. Due to its insufficient image resolution, the microtomography was sometimes unable to quantify very small pores, giving low porosity values. The correlation between bulk densities measured by the two methods shows an intermediate efficiency. Although the results presented here indicate that the microCT image analysis is appropriate for quantification of mineral phases, this technique has potential for determination of many other physical properties, such as mechanical, electrical and fluid flow rock properties.
Digital Public Archaeology at Must Farm: A Critical Assessment of Social Media Use for Archaeological Engagement
Authors: Wakefield Christopher
Published: October 2020

Digital public archaeology is increasingly exploring social networks as platforms for online outreach initiatives. Despite a growing body of literature concerning archaeological engagement on social media there are few examinations of such applications in practice. This research critically assesses the current discussions surrounding archaeological social media use before exploring commercial digital outreach at Must Farm, Cambridgeshire. Quantitative examinations of the project's Facebook metrics and qualitative comment analyses are employed to assess whether audiences were meaningfully engaged by these online strategies. The research concludes there is substantial value in using social networks to communicate archaeology and provides recommendations for future applications.
Synthesis of TiN/N-doped TiO2 composite films as visible light active photocatalyst
Authors: Panghulan Glenson R. , Vasquez Magdaleno R. , Edañol Yasmin D. , Chanlek Narong , Payawan Leon M.
Published: October 2020

Titanium nitride/nitrogen-doped titanium oxide (TiN/N-doped TiO2) composite films were synthesized for visible light photodegradation applications. Thin films of TiN were sputter-deposited on precleaned glass substrates in an admixture of argon and nitrogen gases. The grown TiN films were subsequently oxidized in air at 350 °C at 15, 30, and 60 min. Raman spectral analysis revealed the formation of TiO2 with anatase structure at 15 min and transitioned to the rutile structure at longer oxidation times. X-ray photoelectron spectral analysis revealed the formation of N-doped TiO2 from the oxidized Ti. Visible light-induced photodegradation of methylene blue as test analyte showed 30% removal efficiency after exposure to visible light after 2.5 h. The highest degradation efficiency was observed when the anatase phase of TiO2 is the dominant phase in the film. Moreover, N-doping realized the visible light sensitivity of TiO2. This makes the composite film ideal for solar light-driven photodegradation of organic contaminants in wastewater.
Energy distributions of secondary ions for the Ar ion beam sputtering of indium tin oxide
Authors: Bundesmann Carsten , Hellmich Anke
Published: October 2020

The energy distributions of secondary ions for the Ar ion beam sputtering of indium tin oxide were measured in dependence on geometric parameters (ion incidence angle, polar emission angle, scattering angle), ion energy, and O2 background pressure using energy-selective mass spectrometry. The most prevalent ion species were identified to be O+, O2+, Ar+, In+, and Sn+. The energy distributions of O+, In+, and Sn+ ions show a low-energy maximum between 10 and 20 eV, followed by a power-law decay if the scattering angle is γ>90°. If γ<90°, an additional high-energy structure evolves, which is assigned to anisotropy effects, namely, directly sputtered particles. The energy distributions of the Ar+ ions show a low-energy maximum and, in dependence on the scattering angle, up to two additional high-energy structures, which are also assigned to anisotropy effects. Here it is related to direct scattering events. All additional structures show systematic correlations with scattering angle and ion energy. The energy distributions of the O2+ ions exhibit a low-energy maximum followed by a sudden signal drop. There is almost no variation with scattering angle or ion energy. In general, increasing the O2 background pressure results in a decrease of the particle energy due to an energy loss upon interaction with background gas particles. The experimental results are compared and discussed with calculations based on elastic two-particle collision theory and using srim, and Monte Carlo simulations using SDTrimSP.
Conformational states dynamically populated by a kinase determine its function
Authors: Xie Tao , Saleh Tamjeed , Rossi Paolo , Kalodimos Charalampos G.
Published: October 2020

A moving target

Abl kinase is an important signaling protein that is dysregulated in leukemia and other cancers and is the target of inhibitors such as imatinib. Like other kinases, Abl kinase is dynamic, and regulating conformational dynamics is key to regulating activity. Xie
et al.
used nuclear magnetic resonance to show that the Abl kinase domain interconverts between one active and two inactive states. Imatinib stabilizes an inactive conformation, and several resistance mutations act by destabilizing this conformation. In a construct that includes the regulatory domain, depending on the relative arrangement of the kinase and regulatory domains, the kinase domain is stabilized in either the active state or one of the inhibited states. Understanding the conformational dynamics of kinases can be leveraged to design selective drugs.

Science
, this issue p.
eabc2754
Static Growth Promotes PrrF and 2-Alkyl-4(1
H
)-Quinolone Regulation of Type VI Secretion Protein Expression in Pseudomonas aeruginosa
Authors: Brewer Luke K. , Huang Weiliang , Hackert Brandy J. , Kane Maureen A. , Oglesby Amanda G.
Published: October 2020

Host-mediated iron starvation is a broadly conserved signal for microbial pathogens to upregulate expression of virulence traits required for successful infection. Historically, global iron regulatory studies in microorganisms have been conducted in shaking cultures to ensure culture homogeneity, yet these conditions are likely not reflective of growth during infection.
Pseudomonas aeruginosa
is a well-studied opportunistic pathogen and model organism for iron regulatory studies. Iron homeostasis is maintained through the Fur protein and PrrF small regulatory sRNAs, the functions of which are highly conserved in many other bacterial species. In the current study, we examined how static growth affects the known iron and PrrF regulons of
P. aeruginosa
, leading to the discovery of novel PrrF-regulated virulence processes. This study demonstrates how the utilization of distinct growth models can enhance our understanding of basic physiological processes that may also affect pathogenesis.
De Novo
Cholesterol Biosynthesis and Its Trafficking in LAMP-1-Positive Vesicles Are Involved in Replication and Spread of Marek’s Disease Virus
Authors: Boodhoo Nitish , Kamble Nitin , Behboudi Shahriar
Published: October 2020

MDV disrupts lipid metabolism and causes atherosclerosis in MDV-infected chickens; however, the role of cholesterol metabolism in the replication and spread of MDV is unknown. MDV-infected cells do not produce infectious cell-free virus
in vitro
, raising the question about the mechanism involved in the cell-to-cell spread of MDV. In this report, we provide evidence that MDV replication depends on
de novo
cholesterol biosynthesis and uptake. Interruption of cholesterol trafficking within multivesicular bodies (MVBs) by chemical inhibitors or gene silencing reduced MDV titers and cell-to-cell spread. Finally, we demonstrated that MDV gB colocalizes with cholesterol and LAMP-1, suggesting that viral protein trafficking is mediated by LAMP-1-positive vesicles in association with cholesterol. These results provide new insights into the cholesterol dependence of MDV replication.
Two Sides of a Coin: a Zika Virus Mutation Selected in Pregnant Rhesus Macaques Promotes Fetal Infection in Mice but at a Cost of Reduced Fitness in Nonpregnant Macaques and Diminished Transmissibility by Vectors
Authors: Lemos Danilo , Stuart Jackson B. , Louie William , Singapuri Anil , Ramírez Ana L. , Watanabe Jennifer , Usachenko Jodie , Keesler Rebekah I. , Sanchez-San Martin Claudia , Li Tony , Martyn Calla , Oliveira Glenn , Saraf Sharada , Grubaugh Nathan D. , Andersen Kristian G. , Thissen James , Allen Jonathan , Borucki Monica , Tsetsarkin Konstantin A. , Pletnev Alexander G. , Chiu Charles Y. , Van Rompay Koen K. A. , Coffey Lark L.
Published: October 2020

Although Zika virus infection of pregnant women can result in congenital Zika syndrome, the factors that cause the syndrome in some but not all infected mothers are still unclear. We identified a mutation that was present in some ZIKV genomes in experimentally inoculated pregnant rhesus macaques and their fetuses. Although we did not find an association between the presence of the mutation and fetal death, we performed additional studies with ZIKV with the mutation in nonpregnant macaques, pregnant mice, and mosquitoes. We observed that the mutation increased the ability of the virus to infect mouse fetuses but decreased its capacity to produce high levels of virus in the blood of nonpregnant macaques and to be transmitted by mosquitoes. This study shows that mutations in mosquito-borne viruses like ZIKV that increase fitness in pregnant vertebrates may not spread in outbreaks when they compromise transmission via mosquitoes and fitness in nonpregnant hosts.
In-hospital cardiac arrest in critically ill patients with covid-19: multicenter cohort study
Authors: Hayek Salim S , Brenner Samantha K , Azam Tariq U , Shadid Husam R , Anderson Elizabeth , Berlin Hanna , Pan Michael , Meloche Chelsea , Feroz Rafey , O’Hayer Patrick , Kaakati Rayan , Bitar Abbas , Padalia Kishan , Perry Daniel , Blakely Pennelope , Gupta Shruti , Shaefi Shahzad , Srivastava Anand , Charytan David M , Bansal Anip , Mallappallil Mary , Melamed Michal L , Shehata Alexandre M , Sunderram Jag , Mathews Kusum S , Sutherland Anne K , Nallamothu Brahmajee K , Leaf David E
Published: October 2020

Objectives

To estimate the incidence, risk factors, and
outcomes associated with in-hospital cardiac
arrest and cardiopulmonary resuscitation in
critically ill adults with coronavirus disease
2019 (covid-19).

Design

Multicenter cohort study.

Setting

Intensive care units at 68 geographically
diverse hospitals across the United States.

Participants

Critically ill adults (age ≥18 years) with
laboratory confirmed covid-19.

Main outcome measures

In-hospital cardiac arrest within 14 days of
admission to an intensive care unit and
in-hospital mortality.

Results

Among 5019 critically ill patients with
covid-19, 14.0% (701/5019) had in-hospital cardiac
arrest, 57.1% (400/701) of whom received
cardiopulmonary resuscitation. Patients who had
in-hospital cardiac arrest were older (mean age 63
(standard deviation 14)
v
60 (15)
years), had more comorbidities, and were more
likely to be admitted to a hospital with a smaller
number of intensive care unit beds compared with
those who did not have in-hospital cardiac arrest.
Patients who received cardiopulmonary
resuscitation were younger than those who did not
(mean age 61 (standard deviation 14)
v
67 (14) years). The most common
rhythms at the time of cardiopulmonary
resuscitation were pulseless electrical activity
(49.8%, 199/400) and asystole (23.8%, 95/400). 48
of the 400 patients (12.0%) who received
cardiopulmonary resuscitation survived to hospital
discharge, and only 7.0% (28/400) survived to
hospital discharge with normal or mildly impaired
neurological status. Survival to hospital
discharge differed by age, with 21.2% (11/52) of
patients younger than 45 years surviving compared
with 2.9% (1/34) of those aged 80 or older.

Conclusions

Cardiac arrest is common in critically ill
patients with covid-19 and is associated with poor
survival, particularly among older patients.
Serum acylcarnitines and amino acids and risk of type 2 diabetes in a multiethnic Asian population
Authors: Gunther Samuel H , Khoo Chin Meng , Tai E-Shyong , Sim Xueling , Kovalik Jean-Paul , Ching Jianhong , Lee Jeannette J , van Dam Rob M
Published: October 2020

Introduction

We evaluated whether concentrations of serum acylcarnitines and amino acids are associated with risk of type 2 diabetes and can improve predictive diabetes models in an Asian population.

Research design and methods

We used data from 3313 male and female participants from the Singapore Prospective Study Program cohort who were diabetes-free at baseline. The average age at baseline was 48.0 years (SD: 11.9 years), and participants were of Chinese, Malay, and Indian ethnicity. Diabetes cases were identified through self-reported physician diagnosis, fasting glucose and glycated hemoglobin concentrations, and linkage to national disease registries. We measured fasting serum concentrations of 45 acylcarnitines and 14 amino acids. The association between metabolites and incident diabetes was modeled using Cox proportional hazards regression with adjustment for age, sex, ethnicity, height, and parental history of diabetes, and correction for multiple testing. Metabolites were added to the Atherosclerosis Risk in Communities (ARIC) predictive diabetes risk model to assess whether they could increase the area under the receiver operating characteristic curve (AUC).

Results

Participants were followed up for an average of 8.4 years (SD: 2.1 years), during which time 314 developed diabetes. Branched-chain amino acids (HR: 1.477 per SD; 95% CI 1.325 to 1.647) and the alanine to glycine ratio (HR: 1.572; 95% CI 1.426 to 1.733) were most strongly associated with diabetes risk. Additionally, the acylcarnitines C4 and C16-OH, and the amino acids alanine, combined glutamate/glutamine, ornithine, phenylalanine, proline, and tyrosine were significantly associated with higher diabetes risk, and the acylcarnitine C8-DC and amino acids glycine and serine with lower risk. Adding selected metabolites to the ARIC model resulted in a significant increase in AUC from 0.836 to 0.846.

Conclusions

We identified acylcarnitines and amino acids associated with risk of type 2 diabetes in an Asian population. A subset of these modestly improved the prediction of diabetes when added to an established diabetes risk model.
A systematic review of patient-reported outcome measures (PROMs) in cystic fibrosis
Authors: Ratnayake Irushi , Ahern Susannah , Ruseckaite Rasa
Published: October 2020

Background

To determine patient-reported outcome measures (PROMs) which may be suitable for incorporation into the Australian Cystic Fibrosis Data Registry (ACFDR) by identifying PROMs administered in adult and paediatric cystic fibrosis (CF) populations in the last decade.

Methods

We searched MEDLINE, EMBASE, Scopus, CINAHL, PsycINFO and Cochrane Library databases for studies published between January 2009 and February 2019 describing the use of PROMs to measure health-related quality of life (HRQoL) in adult and paediatric patients with CF. Validation studies, observational studies and qualitative studies were included. The search was conducted on 13 February 2019. The COnsensus-based Standards for the selection of health Measurement INstruments Risk of Bias Checklist was used to assess the methodological quality of included studies.

Results

Twenty-seven different PROMs were identified. The most commonly used PROMs were designed specifically for CF. Equal numbers of studies were conducted on adult (32%, n=31), paediatric (35%, n=34) and both (27%, n=26) populations. No PROMs were used within a clinical registry setting previously. The two most widely used PROMs, the Cystic Fibrosis Questionnaire—Revised (CFQ-R) and the Cystic Fibrosis Quality of Life Questionnaire (CFQoL), demonstrated good psychometric properties and acceptability in English-speaking populations.

Discussion

We found that although PROMs are widely used in CF, there is a lack of reporting on the efficacy of methods and timepoints of administration. We identified the CFQ-R and CFQoL as the most suitable for incorporation in the ACFDR as they captured significant effects of CF on HRQoL and were reliable and valid in CF populations. These PROMs will be used in a further qualitative study assessing patients’ with CF and clinicians’ perspectives toward the acceptability and feasibility of incorporating a PROM in the ACFDR.

PROSPERO registration number

CRD42019126931.
Pragmatic evaluation of a coproduced physical activity referral scheme: a UK quasi-experimental study
Authors: Buckley Benjamin JR , Thijssen Dick HJ , Murphy Rebecca C , Graves Lee EF , Cochrane Madeleine , Gillison Fiona , Crone Diane , Wilson Philip M , Whyte Greg , Watson Paula M
Published: October 2020

Objectives

UK exercise referral schemes (ERSs) have been criticised for focusing too much on exercise prescription and not enough on sustainable physical activity (PA) behaviour change. Previously, a theoretically grounded intervention (coproduced PA referral scheme, Co-PARS) was coproduced to support long-term PA behaviour change in individuals with health conditions. The purpose of this study was to investigate the effectiveness of Co-PARS compared with a usual care ERS and no treatment for increasing cardiorespiratory fitness.

Design

A three-arm quasi-experimental trial.

Setting

Two leisure centres providing (1) Co-PARS, (2) usual exercise referral care and one no-treatment control.

Participants

68 adults with lifestyle-related health conditions (eg, cardiovascular, diabetes, depression) were recruited to co-PARS, usual care or no treatment.

Intervention

16-weeks of PA behaviour change support delivered at 4, 8, 12 and 18 weeks, in addition to the usual care 12-week leisure centre access.

Outcome measures

Cardiorespiratory fitness, vascular health, PA and mental well-being were measured at baseline, 12 weeks and 6 months (PA and mental well-being only). Fitness centre engagement (co-PARS and usual care) and behaviour change consultation attendance (co-PARS) were assessed. Following an intention-to-treat approach, repeated-measures linear mixed models were used to explore intervention effects.

Results

Significant improvements in cardiorespiratory fitness (p=0.002) and vascular health (p=0.002) were found in co-PARS compared with usual care and no-treatment at 12 weeks. No significant changes in PA or well-being at 12 weeks or 6 months were noted. Intervention engagement was higher in co-PARS than usual care, though this was not statistically significant.

Conclusion

A coproduced PA behaviour change intervention led to promising improvements in cardiorespiratory and vascular health at 12 weeks, despite no effect for PA levels at 12 weeks or 6 months.

Trial registration number

NCT03490747.
Developing a behavioural intervention package to identify and amend incorrect penicillin allergy records in UK general practice and subsequently change antibiotic use
Authors: Santillo Marta , Wanat Marta , Davoudianfar Mina , Bongard Emily , Savic Sinisa , Savic Louise , Porter Catherine , Fielding Joanne , Butler Christopher C , Pavitt Sue , Sandoe Jonathan , Tonkin-Crine Sarah
Published: October 2020

Objectives

To develop a behavioural intervention package to support clinicians and patients to amend incorrect penicillin allergy records in general practice. The intervention aimed to: (1) support clinicians to refer patients for penicillin allergy testing (PAT), (2) support patients to attend for PAT and (3) support clinicians and patients to prescribe or consume penicillin, when indicated, following a negative PAT result.

Methods

Theory-based, evidence-based and person-based approaches were used in the intervention development. We used evidence from a rapid review, two qualitative studies, and expert consultations with the clinical research team to identify the intervention ‘guiding principles’ and develop an intervention plan. Barriers and facilitators to the target behaviours were mapped to behaviour change theory in order to describe the proposed mechanisms of change. In the final stage, think-aloud interviews were conducted to optimise intervention materials.

Results

The collated evidence showed that the key barriers to referral of patients by clinicians were limited experience of referral and limited knowledge of referral criteria and PAT. Barriers for patients attending PAT were lack of knowledge of the benefits of testing and lack of motivation to get tested. The key barriers to the prescription and consumption of first-line penicillin following a negative test result were patient and clinician beliefs about the accuracy of PAT and whether taking penicillin was safe. Intervention materials were designed and developed to address these barriers.

Conclusions

We present a novel behavioural intervention package designed to address the multiple barriers to uptake of PAT in general practice by clinicians and patients. The intervention development details how behaviour change techniques have been incorporated to hypothesise how the intervention is likely to work to help amend incorrect penicillin allergy records. The intervention will go on to be tested in a feasibility trial and randomised controlled trial in England.
Strategies to reduce antibiotic use in women with uncomplicated urinary tract infection in primary care: protocol of a systematic review and meta-analysis including individual patient data
Authors: Heinz Judith , Röver Christian , Furaijat Ghefar , Kaußner Yvonne , Hummers Eva , Debray Thomas , Hay Alastair D , Heytens Stefan , Vik Ingvild , Little Paul , Moore Michael , Stuart Beth , Wagenlehner Florian , Kronenberg Andreas , Ferry Sven , Monsen Tor , Lindbaek Morten , Friede Tim , Gagyor Ildiko
Published: October 2020

Introduction

Uncomplicated urinary tract infection (UTI) in women is a common reason to present in general practice and is usually treated with antibiotics to reduce symptom severity and duration. Results of recent clinical trials indicate that non-antibiotic treatment approaches can also be effective. However, it remains unclear which patients would benefit from antibiotic treatment and which can effectively and safely be treated without antibiotics. This systematic review and meta-analysis aims to estimate the effect of treatment strategies to reduce antibiotic use in comparison with immediate antibiotic treatment and to identify prognostic factors and moderators of treatment effects. A further aim is to identify subgroups of patients benefiting from a specific therapy.

Methods and analysis

A systematic literature search will be performed to identify randomised controlled trials which investigated the effect of treatment strategies to reduce antibiotic use in female adults with uncomplicated UTI compared with immediate antibiotic treatment. Therefore, the primary outcome of the meta-analysis is incomplete recovery. Anonymised individual patient data (IPD) will be collected. Aggregate data will be used for pairwise comparisons of treatment strategies using meta-analysis models with random effects accounting for potential between-study heterogeneity. Potential effect moderators will be explored in meta-regressions. For IPD, generalised linear mixed models will be used, which may be adjusted for baseline characteristics. Interactions of baseline variables with treatment effects will be explored. These models will be used to assess direct comparisons of treatment, but might be extended to networks.

Ethics and dissemination

The local institutional review and ethics board judged the project a secondary analysis of existing anonymous data which meet the criteria for waiver of ethics review. Dissemination of the results will be via published scientific papers and presentations. Key messages will be promoted for example, via social media or press releases.

PROSPERO registration number

CRD42019125804.
Examining the prevalence, correlates and inequalities of undiagnosed hypertension in Nepal: a population-based cross-sectional study
Authors: Hasan Md. Mehedi , Tasnim Fariha , Tariqujjaman Md. , Ahmed Sayem , Cleary Anne , Mamun Abdullah
Published: October 2020

Objective

To examine the prevalence, correlates and sociodemographic inequalities of undiagnosed hypertension in Nepal.

Design

This study used cross-sectional 2016 Nepal Demographic and Health Survey (NDHS) data. Undiagnosed patients with hypertension were defined as an NDHS respondent who was diagnosed as hypertensive (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) during the survey, but never took any prescribed anti-hypertensive medicine to lower/control blood pressure and was never identified as having hypertension by a health professional prior the survey. Multiple binary logistic regression analysis was performed, and Concentration Index was measured.

Setting

Nepal.

Participants

Adult patients with hypertension.

Results

Among 3334 patients with hypertension, 50.4% remained undiagnosed during the survey in Nepal. Adjusted model reveals that patients who were male, belonged to households other than the highest wealth quintile, and lived in province 4 and province 5 were at higher risk of remaining undiagnosed for hypertension. Patients who were ≥65 years of age and were overweight/obese were at lower risk of remaining undiagnosed for hypertension. The poor-rich gap was 24.6 percentage points (Q1=64.1% vs Q5=39.6%) and poor:rich ratio was 1.6 (Q1/Q5=1.6) in the prevalence of undiagnosed hypertension. Undiagnosed hypertension was disproportionately higher among lower socioeconomic status groups (Concentration Index, C=−0.18). Inequalities in the prevalence of undiagnosed hypertension further varied across other geographic locations, including place of residence, ecological zones and administrative provinces.

Conclusions

Undiagnosed hypertension was highly prevalent in Nepal and there were substantial inequalities by sociodemographics and subnational levels. Increasing awareness, strengthening routine screening to diagnose hypertension at primary health service facilities and enactment of social health insurance policy may help Nepal to prevent and control this burden.
Study protocol for a multicentre implementation trial of monotherapy anticoagulation to expedite home treatment of patients diagnosed with venous thromboembolism in the emergency department
Authors: Kline Jeffrey , Adler David , Alanis Naomi , Bledsoe Joseph , Courtney Daniel , D'Etienne James , B Diercks Deborah , Garrett John , Jones Alan E , MacKenzie David , Madsen Troy , Matuskowitz Andrew , Mumma Bryn , Nordenholz Kristen , Pagenhardt Justine , Runyon Michael , Stubblefield William , Willoughby Christopher
Published: October 2020

Introduction

In the USA, many emergency departments (EDs) have established protocols to treat patients with newly diagnosed deep vein thrombosis (DVT) as outpatients. Similar treatment of patients with pulmonary embolism (PE) has been proposed, but no large-scale study has been published to evaluate a comprehensive, integrated protocol that employs monotherapy anticoagulation to treat patients diagnosed with DVT and PE in the ED.

Methods and analysis

This protocol describes the implementation of the Monotherapy Anticoagulation To expedite Home treatment of Venous ThromboEmbolism (MATH-VTE) study at 33 hospitals in the USA. The study was designed and executed to meet the requirements for the Standards for Reporting Implementation Studies guideline. The study was funded by investigator-initiated awards from industry, with Indiana University as the sponsor. The study principal investigator and study associates travelled to each site to provide on-site training. The protocol identically screens patients with both DVT or PE to determine low risk of death using either the modified Hestia criteria or physician judgement plus a negative result from the simplified PE severity index. Patients must be discharged from the ED within 24 hours of triage and treated with either apixaban or rivaroxaban. Overall effectiveness is based upon the primary efficacy and safety outcomes of recurrent VTE and bleeding requiring hospitalisation respectively. Target enrolment of 1300 patients was estimated with efficacy success defined as the upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0%. Thirty-three hospitals in 17 states were initiated in 2016–2017.

Ethics and dissemination

All sites had Institutional Review Board approval. We anticipate completion of enrolment in June 2020; study data will be available after peer-reviewed publication. MATH-VTE will provide information from a large multicentre sample of US patients about the efficacy and safety of home treatment of VTE with monotherapy anticoagulation.
Exploring views and experiences of how infections are detected and managed in practice by nurses, care workers and manager’s in nursing homes in England and Sweden: a survey protocol
Authors: Carey N , Alkhamees Nouf , Cox Anna , Sund-Levander Marta , Tingström Pia , Mold Freda
Published: October 2020

Introduction

In order to avoid unnecessary hospital admission and associated complications, there is an urgent need to improve the early detection of infection in nursing home residents. Monitoring signs and symptoms with checklists or aids called decision support tools may help nursing home staff to detect infection in residents, particularly during the current COVID-19 pandemic.

We plan to conduct a survey exploring views and experiences of how infections are detected and managed in practice by nurses, care workers and managers in nursing homes in England and Sweden.

Methods and analysis

An international cross-sectional descriptive survey, using a pretested questionnaire, will be used to explore nurses, care workers and managers views and experiences of how infections are detected and managed in practice in nursing homes. Data will be analysed descriptively and univariate associations between personal and organisational factors explored. This will help identify important factors related to awareness, knowledge, attitudes, belief and skills likely to affect future implementation of a decision support tool for the early detection of infection in nursing home residents.

Ethics and dissemination

This study was approved using the self-certification process at the University of Surrey and Linköping University ethics committee (Approval 2018/514-32) in 2018. Study findings will be disseminated through community/stakeholder/service user engagement events in each country, publication in academic peer-reviewed journals and conference presentations. A LAY summary will be provided to participants who indicate they would like to receive this information.

This is the first stage of a plan of work to revise and evaluate the Early Detection of Infection Scale (EDIS) tool and its effect on managing infections and reducing unplanned hospital admissions in nursing home residents. Implementation of the EDIS tool may have important implications for the healthcare economy; this will be explored in cost–benefit analyses as the work progresses.
Feasibility study of eye movement desensitisation and reprocessing (EMDR) in people with an at-risk mental state (ARMS) for psychosis: study protocol
Authors: Strelchuk Daniela , Wiles Nicola , Turner Katrina M , Derrick Catherine , Zammit Stan
Published: October 2020

Introduction

Trauma can play an important role in the development of psychosis, yet no studies have investigated whether a trauma-focused psychological therapy could prevent the onset of psychosis in people at high risk of developing this condition. This study aims to establish whether it would be feasible to conduct a multicentre randomised controlled trial (RCT) to investigate the clinical and cost-effectiveness of eye movement desensitisation and reprocessing (EMDR) therapy to prevent the onset of psychosis in people with an at-risk mental state (ARMS).

Methods/analysis

This is a single-arm trial with a nested qualitative study where all participants (target n=20) will be offered EMDR. Eligible participants are those who meet criteria for ARMS; have experienced a traumatic event before the onset of ARMS symptomatology; and have at least one symptom of post-traumatic stress disorder (PTSD). Participants will be followed up at 4, 8 and 12 months after the baseline assessment. The primary outcome measure is transition to psychosis, and secondary outcome measures include severity of psychotic symptoms, PTSD, depression, anxiety, impaired functioning, health status and resource use. The analysis will aim to establish the rates of recruitment and retention for a large-scale RCT. Interviews with therapists and patients will explore their views of the study and their experiences of delivering or receiving EMDR.

Ethics and dissemination

This protocol has been approved by the South West-Cornwall and Plymouth Research Ethics Committee (Reference 18/SW/0037). Findings will be disseminated through journal publications, conference presentations and meetings with service users, their families, mental health professionals and commissioners.

Trial registration number

ISRCTN31976295.
Feasibility randomised controlled trial examining the effects of the Anti-Doping Values in Coach Education (ADVICE) mobile application on doping knowledge and attitudes towards doping among grassroots coaches
Authors: Nicholls Adam Robert , Fairs Lucas R W , Plata-Andrés Mar , Bailey Richard , Cope Edward , Madigan Daniel , Koenen Katrin , Glibo Iva , Theodorou Nikolaos C , Laurent Jean-Francois , Garcia Gaetan , Chanal Benoit
Published: October 2020

Objectives

Sports coaches are influential in whether athletes dope, but receive very little antidoping education, particularly within entry-level coaching qualifications. We tested the feasibility of an antidoping intervention, delivered via a mobile application, which was designed to increase coaches’ knowledge of doping and to reduce favourable doping attitudes.

Methods

A two-arm randomised controlled trial, with grassroots coaches who coach young amateur athletes aged between 14 and 18 years of age, was conducted. The Anti-Doping Values in Coach Education (ADVICE) mobile application included modules on fair play, substances, nutritional supplements, rules and leadership. The primary outcome was the change in doping knowledge, 6 weeks after receiving the mobile application. The secondary outcome was changes in doping attitudes.

Results

Grassroots coaches (n=200; aged between 18 and 71 years, with between 1 and 42 years of coaching experience) from 29 different countries completed baseline assessments, and 85 completed follow-up assessments, and were included in mixed analysis of variance analyses. The intervention increased coaches’ knowledge about doping and also reduced favourable doping attitudes in the experimental arm.

Conclusion

The ADVICE mobile application is a feasible method for delivering and increasing grassroots coaches’ knowledge of banned substances and the potential side effects of doping. Mobile application-based resources could facilitate a much wider dissemination of antidoping education.
Parameters associated with ventricular arrhythmias in mitral valve prolapse with significant regurgitation
Authors: van Wijngaarden Aniek L , de Riva Marta , Hiemstra Yasmine Lisanne , van der Bijl Pieter , Fortuni Federico , Bax Jeroen J , Delgado Victoria , Ajmone Marsan Nina
Published: October 2020

Objective

Mitral valve prolapse (MVP) has been associated with ventricular arrhythmias (VA), but little is known about VA in patients with significant primary mitral regurgitation (MR). Our aim was to describe the prevalence of symptomatic VA in patients with MVP (fibro-elastic deficiency or Barlow’s disease) referred for mitral valve (MV) surgery because of moderate-to-severe MR, and to identify clinical, electrocardiographic, standard and advanced echocardiographic parameters associated with VA.

Methods

610 consecutive patients (64±12 years, 36% female) were included. Symptomatic VA was defined as symptomatic and frequent premature ventricular contractions (PVC, Lown grade ≥2), non-sustained or sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) without ischaemic aetiology.

Results

A total of 67 (11%) patients showed symptomatic VA, of which 3 (4%) had VF, 3 (4%) sustained VT, 27 (40%) non-sustained VT and 34 (51%) frequent PVCs. Patients with VA were significantly younger, more often female and showed T-wave inversions; furthermore, they showed significant MV morphofunctional abnormalities, such as mitral annular disjunction (39% vs 20%, p<0.001), and dilatation (annular diameter 37±5 mm vs 33±6 mm, p<0.001), lower global longitudinal strain (GLS 20.9±3.1% vs 22.0±3.6%, p=0.032) and prolonged mechanical dispersion (45±12 ms vs 38±14 ms, p=0.003) as compared with patients without VA. Female sex, increased MV annular diameter, lower GLS and prolonged mechanical dispersion were identified as independent associates of symptomatic VA.

Conclusion

In patients with MVP with moderate-to-severe MR, symptomatic VA are relatively frequent and associated with significant MV annular abnormalities, subtle left ventricular function impairment and heterogeneous contraction. Assessment of these parameters might help decision-making over further diagnostic analyses and improve risk-stratification.
Evaluating the added predictive ability of MMP-9 in serum for Kawasaki disease with coronary artery lesions
Authors: Wang Lixia , Yang Yinan , Cui Quanmiao , Cui Ya , Li Qiaoe , Che Xinyao , Wang Cong , Quan Peiqin , Hu Xiaobin
Published: October 2020

To investigate the predictive ability of serum matrix metalloproteinase-9 (MMP-9) in the acute phase of Kawasaki disease (KD) with coronary artery lesions (CALs). Patients with KD hospitalized in Lanzhou University Second Hospital, Northwest China, from November 2015 to January 2018 were retrospectively reviewed, and clinical trial indicators and peripheral blood specimens were collected before intravenous immunoglobulin therapy treatment. The independent risk factors were determined using multivariate regression analysis. The net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to quantitatively evaluate the ability of MMP-9 to improve the efficiency of predicting KD with CALs. The white cell, neutrophil percentage, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were higher in patients with higher MMP-9, and the monocyte percentage was higher in patients with lower MMP-9. Logistic regression analysis revealed that long-term fever; elevated CRP, ESR, platelets (PLT), and MMP-9; and low albumin (ALB) levels were independent predictors of KD with CALs. A predictive model of KD with CALs using fever duration, CRP, ESR, PLT, and ALB showed significantly improved predictive ability when MMP-9 was added to the model (the area under the curve increased by 0.02; no change in sensitivity; specificity increased from 81.48% to 87.04%; NRI value: 13.46%; IDI value: 5.00%, p<0.05). Adding MMP-9 to traditional risk factors may improve prediction of CALs, the overall predictive ability of model 2 was increased by 5%.
CDK4/6 inhibition enhances antitumor efficacy of chemotherapy and immune checkpoint inhibitor combinations in preclinical models and enhances T-cell activation in patients with SCLC receiving chemotherapy
Authors: Lai Anne Y , Sorrentino Jessica A , Dragnev Konstantin H , Weiss Jared M , Owonikoko Taofeek K , Rytlewski Julie A , Hood Jill , Yang Zhao , Malik Rajesh K , Strum Jay C , Roberts Patrick J
Published: October 2020

Background

Combination treatment with chemotherapy and immune checkpoint inhibitors (ICIs) has demonstrated meaningful clinical benefit to patients. However, chemotherapy-induced damage to the immune system can potentially diminish the efficacy of chemotherapy/ICI combinations. Trilaciclib, a highly potent, selective and reversible cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor in development to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy, has demonstrated proof of concept in recent clinical trials. Furthermore, CDK4/6 inhibition has been shown to augment T-cell activation and antitumor immunity in preclinical settings. Therefore, addition of trilaciclib has the potential to further enhance the efficacy of chemotherapy and ICI combinations.

Methods

In murine syngeneic tumor models, a schedule of 3 weekly doses of trilaciclib was combined with chemotherapy/ICI regimens to assess the effect of transient CDK4/6 inhibition on antitumor response and intratumor T-cell proliferation and function. Peripheral T-cell status was also analyzed in patients with small cell lung cancer (SCLC) treated with chemotherapy with or without trilaciclib to gain insights into the effect of transient exposure of trilaciclib on T-cell activation.

Results

Preclinically, the addition of trilaciclib to chemotherapy/ICI regimens enhanced antitumor response and overall survival compared with chemotherapy and ICI combinations alone. This effect is associated with the modulation of the proliferation and composition of T-cell subsets in the tumor microenvironment and increased effector function. Transient exposure of trilaciclib in patients with SCLC during chemotherapy treatment both preserved and increased peripheral lymphocyte counts and enhanced T-cell activation, suggesting that trilaciclib not only preserved but also enhanced immune system function.

Conclusions

Transient CDK4/6 inhibition by trilaciclib was sufficient to enhance and prolong the duration of the antitumor response by chemotherapy/ICI combinations, suggesting a role for the transient cell cycle arrest of tumor immune infiltrates in remodeling the tumor microenvironment. These results provide a rationale for combining trilaciclib with chemotherapy/ICI regimens to improve antitumor efficacy in patients with cancer.