bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of an orally administered DGAT2 inhibitor alone or coadministered with a liver-targeted ACC inhibitor in adults with non-alcoholic steatohepatitis (NASH): rationale and design of the phase II, dose-ranging, dose-finding, randomised, placebo-controlled MIRNA (Metabolic Interventions to Resolve NASH with fibrosis) study
Authors: Amin Neeta B , Darekar Amanda , Anstee Quentin M , Wong Vincent Wai-Sun , Tacke Frank , Vourvahis Manoli , Lee Douglas S , Charlton Michael , Alkhouri Naim , Nakajima Atsushi , Yunis Carla 
Published: March 2022

IntroductionSmall molecule inhibitors of the terminal step in intrahepatic triglyceride synthesis (diacylglycerol acyltransferase 2 inhibitor (DGAT2i, PF-06865571, ervogastat)) and upstream blockade ofde novolipogenesis via acetyl-coenzyme A carboxylase inhibitor (ACCi, PF-05221304, clesacostat) showed promise in reducing hepatic steatosis in early clinical trials. This study assesses efficacy and safety of these metabolic interventions to resolve non-alcoholic steatohepatitis (NASH) with fibrosis.Methods and analysisThis phase II, randomised, dose-ranging, dose-finding study evaluates DGAT2i 25–300 mg two times per day (BID) or 150–300 mg once a day, DGAT2i 150–300 mg BID+ACCi 5–10 mg BID coadministration or matching placebo in a planned 450 adults with biopsy-confirmed NASH and liver fibrosis stages 2–3 from approximately 220 sites in 11 countries across North America, Europe and Asia. A triage approach including double-confirmation via non-invasive markers is included prior to screening/baseline liver biopsy. On confirmation of histological diagnosis, participants enter a ≥6-week run-in period, then a 48-week double-blind, double-dummy dosing period. The primary endpoint is the proportion of participants achieving histological NASH resolution without worsening fibrosis, ≥1 stage improvement in fibrosis without worsening NASH, or both, assessed by central pathologists. Other endpoints include assessment of hepatic steatosis (imaging substudy), overall safety and tolerability, and evaluation of blood-based biomarkers and quantitative ultrasound parameters over time.Ethics and disseminationMetabolic Interventions to Resolve NASH with fibrosis (MIRNA) is conducted in accordance with the Declaration of Helsinki and Council for International Organisations of Medical Sciences (CIOMS) International Ethical Guidelines, International Council on Harmonisation Good Clinical Practice guidelines, applicable laws and regulations, including privacy laws. Local independent review board/ethics committees (IRB/ECs) review/approve the protocol, any amendments, informed consent and other forms. Participants provide written informed consent. Details of all IRB/ECs, as well as results, will be published in a peer-reviewed journal and publicly disclosed through ClinicalTrials.gov, EudraCT, and/orwww.pfizer.comand other public registries as per applicable local laws/regulations.Trial registration numberNCT04321031.
Protocol for a randomised controlled trial investigating an intervention to boost decentering in response to distressing mental experiences during adolescence: the decentering in adolescence study (DECADES)
Authors: Bennett Marc P , Knight Rachel Clare , Dunning Darren , Archer-Boyd Alan , Blakemore Sarah-Jayne , Dalmaijer Edwin , Ford Tamsin , Williams J Mark G , Clegg Hannah , Kuyken Willem , So Tierney , Wright Gemma , Lenaert Bert , Vainre Maris , Watson Peter ,   MYRIAD Team, Dalgleish Tim 
Published: March 2022

IntroductionDecentering describes the ability to voluntarily adopt an objective self-perspective from which to notice internal, typically distressing, stressors (eg, difficult thoughts, memories and feelings). The reinforcement of this skill may be an active ingredient through which different psychological interventions accrue reductions in anxiety and/or depression. However, it is unclear if decentering can be selectively trained at a young age and if this might reduce psychological distress. The aim of the current trial is to address this research gap.Methods and analysisAdolescents, recruited from schools in the UK and Ireland (n=57 per group, age range=16–19 years), will be randomised to complete 5 weeks of decentering training, or an active control group that will take part in a combination of light physical exercise and cognitive training. The coprimary training outcomes include a self-reported decentering inventory (ie, the Experiences Questionnaire) and the momentary use of decentering in response to psychological stressors, using experience sampling. The secondary mental health outcomes will include self-reported inventories of depression and anxiety symptoms, as well as psychological well-being. Initial statistical analysis will use between-group analysis of covariance to estimate the effect of training condition on self-rated inventories, adjusted for baseline scores. Additionally, experience sampling data will be examined using hierarchical linear models.Ethics and disseminationThis study was approved by the Cambridge Psychology Research Ethics Committee, University of Cambridge (PRE.2019.109). Findings will be disseminated through typical academic routes including poster/paper presentations at (inter)national conferences, academic institutes and through publication in peer-reviewed journals.Trial registration numberISRCTN14329613.
Worldwide prevalence, risk factors and psychological impact of infertility among women: a systematic review and meta-analysis
Authors: Nik Hazlina Nik Hussain , Norhayati Mohd Noor , Shaiful Bahari Ismail , Nik Muhammad Arif Nik Ahmad 
Published: March 2022

ObjectivesTo assess the prevalence, risk factors and psychological impact of infertility among females. This review summarises the available evidence, effect estimates and strength of statistical associations between infertility and its risk factors.Study designSystematic review and meta-analysis.Data sourcesMEDLINE, CINAHL and ScienceDirect were searched through 23 January 2022.Eligibility criteriaThe inclusion criteria involved studies that reported the psychological impact of infertility among women. We included cross-sectional, case–control and cohort designs, published in the English language, conducted in the community, and performed at health institution levels on prevalence, risk factors and psychological impact of infertility in women.Data extraction and synthesisTwo reviewers independently extracted and assess the quality of data using the Joanna Briggs Institute Meta-Analysis. The outcomes were assessed with random-effects model and reported as the OR with 95% CI using the Review Manager software.ResultsThirty-two studies with low risk of bias involving 124 556 women were included. The findings indicated the overall pooled prevalence to be 46.25% and 51.5% for infertility and primary infertility, respectively. Smoking was significantly related to infertility, with the OR of 1.85 (95% CI 1.08 to 3.14) times higher than females who do not smoke. There was a statistical significance between infertility and psychological distress among females, with the OR of 1.63 (95% CI 1.24 to 2.13). A statistical significance was noted between depression and infertility among females, with the OR of 1.40 (95% CI 1.11 to 1.75) compared with those fertile.ConclusionsThe study results highlight an essential and increasing mental disorder among females associated with infertility and may be overlooked. Acknowledging the problem and providing positive, supportive measures to females with infertility ensure more positive outcomes during the therapeutic process. This review is limited by the differences in definitions, diagnostic cut points, study designs and source populations.PROSPERO registration numberCRD42021226414.
Patients presenting to an acute general hospital with acute mental health needs: a retrospective observational cohort study
Authors: Cann Johnathon , Barter Reece , Battle Joseph , Schwenck Jonas , Anakwe Raymond 
Published: March 2022

ObjectivesTo examine the numbers and patterns of patients presenting to an urban acute general hospital with acute mental health presentations and to further investigate any variation related to the COVID-19 pandemic.DesignRetrospective observational cohort study.SettingAn urban acute general hospital in London, UK, comprising of five sites and two emergency departments. The hospital provides tertiary level general acute care but is not an acute mental health services provider. There is an inpatient liaison psychiatry service.Participants358 131 patients attended the emergency departments of our acute general hospital during the study period. Of these, 14 871 patients attended with an acute mental health presentation. A further 14 947 patients attending with a physical illness were also noted to have a concurrent recorded mental health diagnosis.ResultsLarge numbers of patients present to our acute general hospital with mental health illness even though the organisation does not provide mental health services other than inpatient liaison psychiatry. There was some variation in the numbers and patterns of presentations related to the COVID-19 pandemic. Patient numbers reduced to a mean of 9.13 (SD 3.38) patients presenting per day during the first ‘lockdown’ compared with 10.75 (SD 1.96) patients per day in an earlier matched time period (t=3.80, p<0.01). Acute mental health presentations following the third lockdown increased to a mean of 13.84 a day.ConclusionsLarge numbers of patients present to our acute general hospital with mental health illness. This suggests a need for appropriate resource, staffing and training to address the needs of these patients in a non-mental health provider organisation and subsequent appropriate transfer for timely treatment. The COVID-19 pandemic and the resulting lockdowns have resulted in variation in the numbers and patterns of patients presenting with acute mental health illness but these presentations are not new. Considerable work is still needed to provide integrated care which addresses the physical and mental healthcare needs of patients presenting to acute and general hospitals.
Accuracy of telephone triage for predicting adverse outcomes in suspected COVID-19: an observational cohort study
Authors: Marincowitz Carl , Stone Tony , Bath Peter , Campbell Richard , Turner Janette Kay , Hasan Madina , Pilbery Richard , Thomas Benjamin David , Sutton Laura , Bell Fiona , Biggs Katie , Hopfgartner Frank , Mazumdar Suvodeep , Petrie Jennifer , Goodacre Steve 
Published: March 2022

ObjectiveTo assess accuracy of telephone triage in identifying need for emergency care among those with suspected COVID-19 infection and identify factors which affect triage accuracy.DesignObservational cohort study.SettingCommunity telephone triage provided in the UK by Yorkshire Ambulance Service NHS Trust (YAS).Participants40 261 adults who contacted National Health Service (NHS) 111 telephone triage services provided by YAS between 18 March 2020 and 29 June 2020 with symptoms indicating COVID-19 infection were linked to Office for National Statistics death registrations and healthcare data collected by NHS Digital.OutcomeAccuracy of triage disposition was assessed in terms of death or need for organ support up to 30 days from first contact.ResultsCallers had a 3% (1200/40 261) risk of serious adverse outcomes (death or organ support). Telephone triage recommended self-care or non-urgent assessment for 60% (24 335/40 261), with a 1.3% (310/24 335) risk of adverse outcomes. Telephone triage had 74.2% sensitivity (95% CI: 71.6 to 76.6%) and 61.5% specificity (95% CI: 61% to 62%) for the primary outcome. Multivariable analysis suggested respiratory comorbidities may be overappreciated, and diabetes underappreciated as predictors of deterioration. Repeat contact with triage service appears to be an important under-recognised predictor of deterioration with 2 contacts (OR 1.77, 95% CI: 1.14 to 2.75) and 3 or more contacts (OR 4.02, 95% CI: 1.68 to 9.65) associated with false negative triage.ConclusionPatients advised to self-care or receive non-urgent clinical assessment had a small but non-negligible risk of serious clinical deterioration. Repeat contact with telephone services needs recognition as an important predictor of subsequent adverse outcomes.
Optimising GPs’ communication of advice to facilitate patients’ self-care and prompt follow-up when the diagnosis is uncertain: a realist review of ‘safety-netting’ in primary care
Authors: Friedemann Smith Claire , Lunn Hannah , Wong Geoff , Nicholson Brian D 
Published: March 2022

BackgroundSafety-netting has become best practice when dealing with diagnostic uncertainty in primary care. Its use, however, is highly varied and a lack of evidence-based guidance on its communication could be harming its effectiveness and putting patient safety at risk.ObjectiveTo use a realist review method to produce a programme theory of safety-netting, that is, advice and support provided to patients when diagnosis or prognosis is uncertain, in primary care.MethodsFive electronic databases, web searches, and grey literature were searched for studies assessing outcomes related to understanding and communicating safety-netting advice or risk communication, or the ability of patients to self-care and re-consult when appropriate. Characteristics of included documents were extracted into an Excel spreadsheet, and full texts uploaded into NVivo and coded. A random 10% sample was independently double -extracted and coded. Coded data wasere synthesised and itstheir ability to contribute an explanation for the contexts, mechanisms, or outcomes of effective safety-netting communication considered. Draft context, mechanism and outcome configurations (CMOCs) were written by the authors and reviewed by an expert panel of primary care professionals and patient representatives.Results95 documents contributed to our CMOCs and programme theory. Effective safety-netting advice should be tailored to the patient and provide practical information for self-care and reconsultation. The importance of ensuring understanding and agreement with advice was highlighted, as was consideration of factors such as previous experiences with healthcare, the patient’s personal circumstances and the consultation setting. Safety-netting advice should be documented in sufficient detail to facilitate continuity of care.ConclusionsWe present 15 recommendations to enhance communication of safety-netting advice and map these onto established consultation models. Effective safety-netting communication relies on understanding the information needs of the patient, barriers to acceptance and explanation of the reasons why the advice is being given. Reduced continuity of care, increasing multimorbidity and remote consultations represent threats to safety-netting communication.
Changes in heart failure management and long-term mortality over 10 years: observational study
Authors: Bottle Alex , Newson Roger , Faitna Puji , Hayhoe Benedict , Cowie Martin R 
Published: March 2022

ObjectivesTo estimate the long-term survival of two cohorts of people diagnosed with heart failure 10 years apart and to assess differences in patient characteristics, clinical guideline compliance and survival by diagnosis setting.MethodsData for patients aged 18 and over with a new diagnosis of heart failure in the Clinical Practice Research Datalink in 2001–2002 (5966 patients in 156 practices) and 2011–2012 (12 827 patients in 331 practices). Survival rates since diagnosis were described using Kaplan-Meier plots. Compliance with national guidelines was summarised.Results2011/2012 patients were older than those diagnosed a decade before, with lower blood pressure and cholesterol but more comorbidity and healthcare contacts. For those diagnosed in 2001/2002, the 5-year survival was 40.0% (40.2% in the 2011/2012 cohort), 10-year survival was 20.8%, and 15-year survival 11.1%. Improvement in survival between the two time periods was seen only in those diagnosed in primary care (5-year survival 46.0% vs 57.4%, compared with 33.9% and 32.6% for hospital-diagnosed patients).Beta-blocker use rose from 24.3% to 39.1%; renin–angiotensin system blockers rose from 31.8% to 54.3% (both p<0.001). There was little change for loop diuretics and none for thiazide diuretics. For the 9963 patients with symptoms recorded by their general practitioner before diagnosis, brain natriuretic peptide (BNP) testing was low, but echocardiogram use rose from 8.3% to 19.3%, and specialist referral rose from 7.2% to 24.6% (all p<0.001).ConclusionsThe 10 years saw some long-term survival gains but only modest improvement in national clinical guideline compliance, from a low baseline, despite the introduction of national initiatives.
Rationale and design of a stepped wedge cluster randomised trial to improve acute reperfusion treatment quality for stroke: IMPROVE stroke care in China
Authors: Li Zixiao , Wang Chunjuan , Zhang Xinmiao , Zong Lixia , Zhou Hongyu , Gu Hongqiu , Jiang Yong , Pan Yuesong , Meng Xia , Zhou Qi , Zhao Haifen , Yang Xin , Wang Meng , Xiong Yunyun , Zhao Xingquan , Wang Yilong , Liu Liping , Ma Xudong , Morgan Louise , Xian Ying , Schwamm Lee H , Wang Yongjun 
Published: March 2022

BackgroundReperfusion therapy is the most effective treatment for acute ischaemic stroke (AIS) but remains underutilised in China. There is an urgent need to develop tailored strategies to increase adherence to intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) within the guideline-recommended time window for eligible patients.AimsThis study aims to investigate the efficacy of a comprehensive quality improvement intervention on adherence to guideline-recommended reperfusion therapy for patients with AIS in China.DesignThe Improve Acute Reperfusion Treatment Quality for Stroke in China (IMPROVE Stroke Care in China) trial is designed as a stepped wedge cluster randomised trial within 51 hospitals. We developed the comprehensive intervention ‘STEP’ (Strategies, Toolkit, Exploration, Paradigm) to promote the reconstruction of workflow in stroke centres and shorten in-hospital delay of reperfusion treatment for patients with AIS. The participating hospitals (clusters) were randomised to three groups (cohorts) for different predefined steps to intervention implementation. The primary outcome was the adherent rate of IVT or EVT for eligible patients within the time window. The sample size was estimated to be 7644, and was determined by the number of cases to be enrolled in five study periods to detect a relative increase of 30% (from 19% to 25%) with 90% power and intraclass correlation coefficient of 0.03. All efficacy analyses will be conducted based on the intention-to-treat principle. The primary outcome will be analysed using a mixed-effects logistic regression with a random effect for the cluster (hospital), and a fixed effect for the strategy and period.ConclusionsIf the efficacy is well established, this targeted comprehensive intervention STEP will inform national strategies to increase adherence to guideline-recommended performance on reperfusion therapy.Trial registration numberclinicaltrials.gov Identifier:NCT003578107
Can dark matter–dark energy interaction alleviate the cosmic coincidence problem?
Authors: Jesus J. F. , Escobal A. A. , Benndorf D. , Pereira S. H. 
Published: March 2022

AbstractIn this paper we study a model of interacting dark energy–dark matter where the ratio between these components is not constant, changing from early to late times in such a way that the model can solve or alleviate the cosmic coincidence problem (CP). The interaction arises from an assumed relation of the form $$\rho _x\propto \rho _d^\alpha $$

ρ
x

∝

ρ
d
α

, where $$\rho _x$$

ρ
x

and $$\rho _d$$

ρ
d

are the energy densities of dark energy and dark matter components, respectively, and $$\alpha $$
α
is a free parameter. For a dark energy equation of state parameter $$w=-1$$

w
=
-
1

we found that, if $$\alpha =0$$

α
=
0

, the standard $$\Lambda $$
Λ
CDM model is recovered, where the coincidence problem is unsolved. For $$0<\alpha <1$$

0
<
α
<
1

, the CP would be alleviated and for $$\alpha \sim 1$$

α
∼
1

, the CP would be solved. The dark energy component is analyzed with both $$w=-1$$

w
=
-
1

and $$w\ne -1$$

w
≠
-
1

. Using Supernovae type Ia and Hubble parameter data constraints, in the case $$w=-1$$

w
=
-
1

we find $$\alpha =0.109^{+0.062}_{-0.072}$$

α
=
0
.

109

-
0.072

+
0.062

at 68% C.L., and the CP is alleviated. For $$w\ne -1$$

w
≠
-
1

, a degeneracy arises on the w–$$\alpha $$
α
plane. In order to break such degeneracy we add cosmic microwave background distance priors and baryonic acoustic oscillations data to the constraints, yielding $$\alpha =-0.075\pm 0.046$$

α
=
-
0.075
±
0.046

at 68% C.L.. In this case we find that the CP is not alleviated even for 2$$\sigma $$
σ
interval for $$\alpha $$
α
. Furthermore, this last model is discarded against flat $$\Lambda $$
Λ
CDM according to BIC analysis.
Multiple Vulvar Giant Fibroepithelial Polyps: A Rare Case Occurrence
Authors: Kurniadi Andi , Rinaldi Andi , Yulianti Herry , Bazar Abi Ryamafi , Prasetyawati Rose Dita , Tjandraprawira Kevin Dominique 
Published: March 2022

Fibroepithelial polyps or acrochordons are benign skin tumors of mesenchymal and ectodermal origin. They are seen in 25% of the population, and their frequency increases with age. They are often found in areas with skin folds, such as the neck, axilla, submandibular, or inguinal region. However, they can also be located in the genital tract. Hormone imbalances may facilitate the development of fibroepithelial polyp s (e.g., high levels of estrogen and progesterone during pregnancy). Larger lesions are likely to arise from the proliferation of mesenchymal cells within the hormonally sensitive subepithelial stromal layer of the lower. Generally, their size does not exceed 5 millimeters. We present a 28-year-old patient with multiple giant fibroepithelial polyps with size of

20
×
12
×
8

cm

and

9
×
4
×
2

cm

, located on both sides of her vulva. Herein, we presented our patient along with the review of current literature pertaining to the diagnosis and the treatment of fibroepithelial polyps (FEPs) and the factors leading to excessive growth.