bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zinc acetate lozenges for the treatment of the common cold: a randomised controlled trial
Authors: Hemilä Harri , Haukka Jari , Alho Marianne , Vahtera Jussi , Kivimäki Mika 
Published: January 2020

ObjectiveTo examine a commercially available zinc acetate lozenge for treating the common cold.DesignRandomised, double-blinded, placebo-controlled trial.SettingWorking population in Finland.ParticipantsWe included men and women aged ≥18 years who usually had ≥1 cold per winter. Exclusions were pregnancy, lactation, chronic runny nose or chronic cough.InterventionWe randomised 253 participants to receive a package of lozenges to be taken if they caught the common cold. Of the 253 participants, 88 contracted the common cold and 87 were included in our primary analysis. Zinc acetate lozenges contained 13 mg elemental zinc and placebo lozenges contained sucrose octa-acetate to camouflage the taste of zinc. Instruction to use was six times per day for the maximum of 5 days.Primary outcomeRate of recovery from the common cold analysed by Cox regression.ResultsThere was no difference in the recovery rate between zinc and placebo participants during the 10-day follow-up (rate ratio for zinc vs placebo=0.68, 95% CI 0.42 to 1.08; p=0.10). The recovery rate for the two groups was similar during the 5-day intervention, but for 2 days after the end of zinc/placebo use, the zinc participants recovered significantly slower compared with the placebo participants (p=0.003). In the zinc group, 37% did not report adverse effects, the corresponding proportion being 69% in the placebo group.ConclusionsA commercially available zinc acetate lozenge was not effective in treating the common cold when instructed to be used for 5 days after the first symptoms. Taste has been a common problem in previous zinc lozenge trials, but a third of zinc participants did not complain of any adverse effects. More research is needed to evaluate the characteristics of zinc lozenges that may be clinically efficacious before zinc lozenges can be widely promoted for common cold treatment.Trial registration numberNCT03309995.
Guidelines about physical activity and exercise to reduce cardiometabolic risk factors: protocol for a systematic review and critical appraisal
Authors: Siedler Madelin , Murad M Hassan , Falck-Ytter Yngve , Dahm Philipp , Mustafa Reem A , Sultan Shahnaz , Morgan Rebecca L 
Published: January 2020

IntroductionPhysical activity can prevent a wide range of diseases, including highly prevalent conditions such as heart disease, diabetes and associated cardiometabolic disorders. Numerous guidelines for the prescription of physical activity and exercise to promote general health and prevent disease are released each year, but the quality of these guidelines is currently unknown. This systematic review and critical appraisal of physical activity and exercise guidelines aims to summarise the current status and quality of these guidelines to provide suggestions to improve the development of future guidelines in this area.Methods and analysisWe will conduct a systematic review of guidelines in Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews and Scopus databases published from database 2000 through 23 October 2019, written in English for the use of physical activity and exercise for the prevention of cardiometabolic disease and related risk factors in otherwise healthy individuals. We will also search the grey literature for additional eligible documents. We will use the Appraisal of Guidelines for Research and Evaluation II tool to assess the quality of eligible recommendations from all included guidelines, as well as perform exploratory analyses on guideline development variables.Ethics and disseminationAs a protocol for the review and critical appraisal of published documents, no potential ethical considerations are discussed. The protocol will guide the development of the review, which will be disseminated to relevant journals for publication.PROSPERO registration numberCRD42019126364
Exploring the lived experiences of pregnancy and early motherhood in Italian women with congenital heart disease: an interpretative phenomenological analysis
Authors: Flocco Serena Francesca , Caruso Rosario , Barello Serena , Nania Tiziana , Simeone Silvio , Dellafiore Federica 
Published: January 2020

ObjectiveThis study explored the lived experiences of women with congenital heart disease (CHD) during pregnancy and early motherhood.DesignQualitative study using semistructured interviews. Data were analysed according to interpretative phenomenological analysis.SettingSan Donato Milanese, Italy.Participants12 adult women during pregnancy or early motherhood.ResultsThree main themes emerged from the analysis that were labelled as follows: ‘Being a woman with CHD’; ‘Being a mother with CHD’; and ‘Don’t be alone’. Mothers described both positive and negative feelings about their pregnancies and transitions from childless women to mothers with CHD. They needed supportive care to improve the management of their health during pregnancy and early motherhood.ConclusionThis study explored the lived experiences of women with CHD during pregnancy and early motherhood. The emerged themes represent an initial framework for implementing theory-grounded educational and supportive strategies that improve self-care, engagement and quality of life for women with CHD. Furthermore, the study’s results provide guidance for operationalising the described experiences into items and domains for future cross-national surveys.
Blood pressure monitoring in high-risk pregnancy to improve the detection and monitoring of hypertension (the BUMP 1 and 2 trials): protocol for two linked randomised controlled trials
Authors: Dougall Greig , Franssen Marloes , Tucker Katherine Louise , Yu Ly-Mee , Hinton Lisa , Rivero-Arias Oliver , Abel Lucy , Allen Julie , Band Rebecca Jane , Chisholm Alison , Crawford Carole , Green Marcus , Greenfield Sheila , Hodgkinson James , Leeson Paul , McCourt Christine , MacKillop Lucy , Nickless Alecia , Sandall Jane , Santos Mauro , Tarassenko Lionel , Velardo Carmelo , Wilson Hannah , Yardley Lucy , Chappell Lucy , McManus Richard J 
Published: January 2020

IntroductionSelf-monitoring of blood pressure (BP) in pregnancy could improve the detection and management of pregnancy hypertension, while also empowering and engaging women in their own care. Two linked trials aim to evaluate whether BP self-monitoring in pregnancy improves the detection of raised BP during higher risk pregnancies (BUMP 1) and whether self-monitoring reduces systolic BP during hypertensive pregnancy (BUMP 2).Methods and analysesBoth are multicentre, non-masked, parallel group, randomised controlled trials. Participants will be randomised to self-monitoring with telemonitoring or usual care. BUMP 1 will recruit a minimum of 2262 pregnant women at higher risk of pregnancy hypertension and BUMP 2 will recruit a minimum of 512 pregnant women with either gestational or chronic hypertension. The BUMP 1 primary outcome is the time to the first recording of raised BP by a healthcare professional. The BUMP 2 primary outcome is mean systolic BP between baseline and delivery recorded by healthcare professionals. Other outcomes will include maternal and perinatal outcomes, quality of life and adverse events. An economic evaluation of BP self-monitoring in addition to usual care compared with usual care alone will be assessed across both study populations within trial and with modelling to estimate long-term cost-effectiveness. A linked process evaluation will combine quantitative and qualitative data to examine how BP self-monitoring in pregnancy is implemented and accepted in both daily life and routine clinical practice.Ethics and disseminationThe trials have been approved by a Research Ethics Committee (17/WM/0241) and relevant research authorities. They will be published in peer-reviewed journals and presented at national and international conferences. If shown to be effective, BP self-monitoring would be applicable to a large population of pregnant women.Trial registration numberNCT03334149
Is austerity responsible for the recent change in mortality trends across high-income nations? A protocol for an observational study
Authors: McCartney Gerry , Fenton Lynda , Minton Jon , Fischbacher Colin , Taulbut Martin , Little Kirsty , Humphreys Ciaran , Cumbers Andrew , Popham Frank , McMaster Robert 
Published: January 2020

IntroductionMortality rates in many high-income countries have changed from their long-term trends since around 2011. This paper sets out a protocol for testing the extent to which economic austerity can explain the variance in recent mortality trends across high-income countries.Methods and analysisThis is an ecological natural experiment study, which will use regression adjustment to account for differences in exposure, outcomes and confounding. All high-income countries with available data will be included in the sample. The timing of any changes in the trends for four measures of austerity (the Alesina-Ardagna Fiscal Index, real per capita government expenditure, public social spending and the cyclically adjusted primary balance) will be identified and the cumulative difference in exposure to these measures thereafter will be calculated. These will be regressed against the difference in the mean annual change in life expectancy, mortality rates and lifespan variation compared with the previous trends, with an initial lag of 2 years after the identified change point in the exposure measure. The role of underemployment and individual incomes as outcomes in their own right and as mediating any relationship between austerity and mortality will also be considered. Sensitivity analyses varying the lag period to 0 and 5 years, and adjusting for recession, will be undertaken.Ethics and disseminationAll of the data used for this study are publicly available, aggregated datasets with no individuals identifiable. There is, therefore, no requirement for ethical committee approval for the study. The study will be lodged within the National Health Service research governance system. All results of the study will be published following sharing with partner agencies. No new datasets will be created as part of this work for deposition or curation.
Atorvastatin for prevention of disease progression and hospitalisation in liver cirrhosis: protocol for a randomised, double-blind, placebo-controlled trial
Authors: Kimer Nina , Grønbæk Henning , Fred Rikard Gøran , Hansen Torben , Deshmukh Atul Shahaji , Mann Mathias , Bendtsen Flemming 
Published: January 2020

IntroductionPatients with liver cirrhosis are often diagnosed late and once complications are present, the 2-year survival is 50%. Increasing evidence supports systemic inflammation and metabolic dysfunction in the hepatic stellate cell as key drivers of progression of cirrhosis. However, there is no registered medication, that targets inflammation and cellular dysfunction in the liver.Methods and analysisIn a randomised double-blind and placebo-controlled trial with atorvastatin for liver cirrhosis, we aim to investigate clinical endpoints of survival, hospitalisations and safety, but also exploratory endpoints of genomics and protein functions in the liver.Ethics and disseminationThere is no registered medication that actively prevents development of complications or systemic inflammation in liver cirrhosis. All patients continue regular clinical management during the trial period. Atorvastatin has been on the market for several years with a safety profile that is acceptable even in patients with liver disease. A beneficial effect of atorvastatin on clinical outcomes in cirrhosis will provide cheap and effective causal treatment for chronic liver disease. The trial is registered by the Danish Data Protection Agency (P-2019–635) and approved by the Danish Medicines Agency (EudraCT 2019-001806-40) and the Scientific Ethics Committee of the Capital Region of Denmark (H-19030643) before initiation. Reporting of the trial will follow the Consolidated Standards of Reporting Trials guidelines for reporting of randomised clinical trials.Trial registration numberThe trial is registered in clinicaltrials.gov (NCT04072601) and in clinicaltrialsregister.eu (EudraCT 2019-001806-40) (Pre-results).
Systematic review: the impact of inflammatory bowel disease-related fatigue on health-related quality of life
Authors: Radford Shellie Jean , McGing Jordan , Czuber-Dochan Wladyslawa , Moran Gordon 
Published: January 2020

BackgroundFatigue is frequently reported in inflammatory bowel disease (IBD) and impacts on health-related quality of life (HRQoL). HRQoL has not been systematically reviewed in IBD fatigue.AimTo investigate what impact IBD fatigue has on HRQoL in adults with IBD.MethodsSystematic searches (CINAHL, EMBASE, PsychINFO, Medline) were conducted on 25 September 2018, restricted to ‘human’, ‘adult’, ‘primary research’ and ‘English language’. Search terms encompassed concepts of ‘fatigue’, ‘IBD’ and ‘HRQoL’. A 5-year time limit (2013–2018) was set to include the most relevant publications. Publications were screened, data extracted and quality appraised by two authors. A narrative synthesis was conducted.ResultsEleven studies were included, presenting data from 2823 participants. Fatigue experiences were significantly related to three HRQoL areas: symptom acceptance, psychosocial well-being and physical activity. Patients reporting high fatigue levels had low symptom acceptance. Psychosocial factors were strongly associated with both fatigue and HRQoL. Higher social support levels were associated with higher HRQoL. Physical activity was impaired by higher fatigue levels, lowering HRQoL, but it was also used as a means of reducing fatigue and improving HRQoL. Quality appraisal revealed methodological shortcomings in a number of studies. Notably, use of multiple measures, comparison without statistical adjustment and fatigue and HRQoL assessment using the same tool were some of the methodological shortcomings.ConclusionPsychosocial factors, symptom management and acceptance and physical activity levels have significant impact on HRQoL. Results support application of psychosocial or exercise interventions for fatigue management. Further exploration of HRQoL factors in IBD fatigue is required, using validated fatigue and HRQoL measures.PROSPERO registration numberCRD42018110005.
UK National Survey of Gastroenterologists’ attitudes and barriers toward therapeutic drug monitoring of anti-TNF therapy in inflammatory bowel disease
Authors: Nigam Gaurav B , Nayeemuddin Shadab , Kontopantelis Evangelos , Hayee Bu'Hussain , Limdi Jimmy K 
Published: January 2020

BackgroundEvidence supports use of therapeutic drug monitoring (TDM) in improving efficacy and cost-effectiveness of anti-tumour necrosis factor (TNF) therapy in inflammatory bowel disease (IBD). Our objective was to assess attitudes and barriers towards TDM use with anti-TNF’s in the UK.MethodsA 17-question survey was distributed to members of the British Society of Gastroenterology by email.ResultsOf 243 respondents (51.6% male), 237 respondents met inclusion criteria. Of these, 46% were consultants (gastroenterologist, GI), 39.2% IBD nurse specialists (clinical nurse specialists, CNS), 14.8% registrars. TDM is used by 96.9% for secondary loss of response; 72.5% for primary non-response and 54.1% used TDM proactively. Barriers were time lag in receiving results (49.8%), lack of awareness of guidelines (46.4%) and cost (29.9%). Clinicians working at a teaching hospital (OR 2.6, 95% CI 0.71 to 9.8), IBD CNS and GI registrars (OR 2.6, 95% CI 0.7 to 10 and OR 1.5, 95% CI 0.3 to 7.2, respectively) were more likely to use TDM. Clinicians practising for >20 years (OR 4.1, 95% CI 0.4 to 41.8) and a large volume IBD practice (>50% IBD patients per month) were more likely to use TDM (OR 45.7, 95% CI 7.5 to 275). Proactive TDM, was more likely to be used in tertiary care (OR 2.25, 95% CI 0.84 to 6.1), IBD CNS (OR 1.2, 95% CI 0.7 to 2.1) and clinicians managing >50% IBD patients per month (OR 10.8, 95% CI 1.3 to 90.3). Clinicians with 5–9 years of experience in practice were more likely to use proactive TDM (OR 2.6 and CI 1.04 to 6.4).ConclusionValidation of point of care and lower cost assays, reduced time lag from test to result, lower cost of testing and dissemination of current recommendations may further optimise treatment strategies.
MiR130b from Schlafen4+MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer
Authors: Ding Lin , Li Qian , Chakrabarti Jayati , Munoz Andres , Faure-Kumar Emmanuelle , Ocadiz-Ruiz Ramon , Razumilava Nataliya , Zhang Guiying , Hayes Michael H , Sontz Ricky A , Mendoza Zoe Elena , Mahurkar Swapna , Greenson Joel K , Perez-Perez Guillermo , Hanh Nguyen Thi Hong , Zavros Yana , Samuelson Linda C , Iliopoulos Dimitrios , Merchant Juanita L 
Published: January 2020

The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach duringHelicobacter-induced spasmolytic polypeptide-expressing metaplasia (SPEM).ObjectiveTo identify the gene products expressed by Slfn4+-MDSCs and to determine how they promote SPEM.DesignWe performed transcriptome analyses for both coding genes (mRNA by RNA-Seq) and non-coding genes (microRNAs using NanoString nCounter) using flow-sorted SLFN4+and SLFN4–cells fromHelicobacter-infected mice exhibiting metaplasia at 6 months postinfection. Thioglycollate-elicited myeloid cells from the peritoneum were cultured and treated with IFNα to induce the T cell suppressor phenotype, expression of MIR130b and SLFN4. MIR130b expression in human gastric tissue including gastric cancer and patient sera was determined by qPCR and in situ hybridisation. Knockdown of MiR130b in vivo inHelicobacter-infected mice was performed using Invivofectamine. Organoids from primary gastric cancers were used to generate xenografts. ChIP assay and Western blots were performed to demonstrate NFκb p65 activation by MIR130b.ResultsMicroRNA analysis identified an increase in MiR130b in gastric SLFN4+cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4+cells and promotedHelicobacter-induced metaplasia. Treating gastric organoids with the MIR130b mimic induced epithelial cell proliferation and promoted xenograft tumour growth.ConclusionTaken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.
Left atrial cross-sectional area is a novel measure of atrial shape associated with cardioembolic strokes
Authors: Tan Timothy C , Nunes Maria Carmo Pereira , Handschumacher Mark , Pontes-Neto Octavio , Park Yong-Hyun , O’Brien Cashel , Piro Victoria , Kim Gyeong-Moon , Helenius Johanna , Zeng Xin , Padilha da Silva Jose Luiz , Furie Karen , Ay Hakan , Hung Judy 
Published: January 2020

ObjectiveCardioembolic (CE) stroke carries significant morbidity and mortality. Left atrial (LA) size has been associated with CE risk. We hypothesised that differential LA remodelling impacts on pathophysiological mechanism of major CE strokes.MethodsA cohort of consecutive patients hospitalised with ischaemic stroke, classified into CE versus non-CE strokes using the Causative Classification System for Ischaemic Stroke were enrolled. LA shape and remodelling was characterised by assessing differences in maximal LA cross-sectional area (LA-CSA) in a cohort of 40 prospectively recruited patients with ischaemic stroke using three-dimensional (3D) echocardiography. Flow velocity profiles were measured in spherical versus ellipsoidal in vitro models to determine if LA shape influences flow dynamics. Two-dimensional (2D) LA-CSA was subsequently derived from standard echocardiographic views and compared with 3D LA-CSA.ResultsA total of 1023 patients with ischaemic stroke were included, 230 (22.5%) of them were classified as major CE. The mean age was 68±16 years, and 464 (45%) were women. The 2D calculated LA-CSA correlated strongly with the LA-CSA measured by 3D in both end-systole and end-diastole. In vitro flow models showed shape-related differences in mid-level flow velocity profiles. Increased LA-CSA was associated with major CE stroke (adjusted relative risk 1.10, 95% CI 1.04 to 1.16; p<0.001), independent of age, gender, atrial fibrillation, left ventricular ejection fraction and CHA2DS2-VASc score. Specifically, the inclusion of LA-CSA in a model with traditional risk factors for CE stroke resulted in signiﬁcant improvement in model performance with the net reclassification improvement of 0.346 (95% CI 0.189 to 0.501; p=0.00001) and the integrated discrimination improvement of 0.013 (95% CI 0.003 to 0.024; p=0.0119).ConclusionsLA-CSA is a marker of adverse LA shape associated with CE stroke, reflecting importance of differential LA remodelling, not simply LA size, in the mechanism of CE risk.
Factors related to adverse events during endovascular coil embolization for ruptured cerebral aneurysms
Authors: Imamura Hirotoshi , Sakai Nobuyuki , Satow Tetsu , Iihara Koji 
Published: January 2020

Background and purposeThe risk factors for adverse events for example, intraprocedural rupture (IPR), ischemic complication within 24 hours, and rebleeding after endovascular coil embolization for a ruptured cerebral aneurysm remain unclear. The aim of this study was to identify significant associated risk factors.MethodsWe retrospectively evaluated data from 5358 patients listed on the Japanese Registry of Neuroendovascular Therapy 3 during 2010–2014.ResultsIPR, ischemic complications, and rebleeding occurred during or after 221 (4.1%), 226 (4.2%), and 63 (1.2%) treatments, respectively. All of the adverse events were significantly associated with the patients’ poor outcomes at 30 days. Multivariate analysis revealed the factors independently related to these adverse events as follows: (1) for IPR: female sex, bifurcation type, <5 mm aneurysm, emergent surgery, local anesthesia, a balloon-assisted technique; (2) for an ischemic complication: poor World Federation World Federation of Neurological Societies (WFNS) grade, wide neck, and stent-assisted technique; (3) for rebleeding: poor WFNS grade, bifurcation type, wide neck, and body filling as the initial result.ConclusionsKnowledge of the risk factors of endovascular coil embolization and paying attention to them are essential for patients’ safe treatment and good outcomes.