bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, efficacy and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade cervical intraepithelial neoplasia associated with human papillomavirus: a systematic review protocol
Authors: Gonçalves Caroline Amélia , Lopes-Júnior Luís Carlos , Nampo Fernando Kenji , Zilly Adriana , Mayer Paulo César Morales , Pereira-da-Silva Gabriela 
Published: July 2019

IntroductionEighty per cent of the sexually active population will get human papillomavirus (HPV) infection, which is the most prevalent sexually transmitted disease worldwide. Persistence of high-grade HPV infection may evolve to a cervical intraepithelial neoplasia (CIN), and these lesions may be precursors of cervical cancer. However, this progression can be prevented by the administration of therapeutic vaccines which use the main oncoproteins responsible for cancer development in an attempt to trigger a more specific and effective immunological response against this disorder. We aim to evaluate the safety, efficacy and immunogenicity of therapeutic vaccines in the treatment of patients with high-grade CIN 2/3 associated with HPV.Methods and analysisA systematic review of clinical trials will be undertaken. Medline, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, Web of Science, Latin American and Caribbean Health Sciences Literature, Scientific Electronic Library Online and Scopus will be searched, with no restriction regarding publication date. Primary outcomes will include measures related to safety, efficacy and the immunogenicity of the therapeutic vaccines used in these patients. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methodological appraisal of the studies will be assessed by the Cochrane Risk-of-Bias Tool for randomised controlled trials, and the quality evidence of the risk of bias in single studies will be evaluated by Grading of Recommendations Assessment, Development and Evaluation. A narrative synthesis will be done for all included studies. Outcomes will be analysed according to the subgroups of HPV type, CIN grade, route of vaccine administration and vaccine type. Also, if sufficient data are available, a meta-analysis will be conducted. The effect sizes will be generated using Hedges’ g score for both fixed and random effect models. I2statistics will be used to assess heterogeneity and identify their potential sources.Ethics and disseminationEthical approval is not required as primary data will not be collected. Findings will be disseminated widely via peer-reviewed publication and in different media, for example, conferences, congresses or symposia.PROSPERO registration numberCRD42017077428.
The effect of smell and taste of milk during tube feeding of preterm infants (the Taste trial): a protocol for a randomised controlled trial
Authors: Beker Friederike , Macey Judith , Liley Helen , Hughes Ian , Davis Peter G , Twitchell Emily , Jacobs Susan 
Published: July 2019

IntroductionSmell and taste of milk are not generally considered when tube feeding preterm infants. Preterm infants have rapid growth, particularly of the brain, and high caloric needs. Enteral feeding is often poorly tolerated which may lead to growth failure and long-term neurodevelopmental impairment. Smell and taste are strong stimulators of digestion and metabolism. We hypothesise that regular smell and taste during tube feeding will improve weight z-scores of very preterm infants at discharge from hospital.Methods and analysisTaste is a randomised, unblinded two-centre trial. Infants born at <29 weeks’ gestation and/or <1250 g at birth and admitted to a participating neonatal intensive care unit are eligible. Randomisation occurs before infants receive two hourly feeds for 24 hours. Infants are randomised to either smell and taste of milk with each tube feed or tube feeding without the provision of smell and taste. The primary outcome is weight z-score at discharge. Secondary outcomes include: days to full enteral feeds, duration of parenteral nutrition, rate of late-onset sepsis, post menstrual age at removal of nasogastric tube and at discharge from hospital, anthropometric data and neurodevelopmental outcomes at 2 years of corrected age.Ethics and disseminationHuman Research Ethics Committees of Mater Misericordiae (trial reference number: HREC/16/MHS/112) and the Royal Women’s Hospital (trial reference number: 17/21) last approved the trial protocol (version 4.2; Date: 18 December 2018) and recruitment commenced in May 2017 and November 2017, respectively. The trial results will be published in a peer-reviewed journal and will be presented at national and international conferences.Trial registration numberACTRN12617000583347.
Development of a point of care system for automated coma prognosis: a prospective cohort study protocol
Authors: Connolly John F , Reilly James P , Fox-Robichaud Alison , Britz Patrick , Blain-Moraes Stefanie , Sonnadara Ranil , Hamielec Cindy , Herrera-Díaz Adianes , Boshra Rober 
Published: July 2019

IntroductionComa is a deep state of unconsciousness that can be caused by a variety of clinical conditions. Traditional tests for coma outcome prediction are based mainly on a set of clinical observations. Recently, certain event-related potentials (ERPs), which are transient electroencephalogram (EEG) responses to auditory, visual or tactile stimuli, have been introduced as useful predictors of a positive coma outcome (ie, emergence). However, such tests require the skills of clinical neurophysiologists, who are not commonly available in many clinical settings. Additionally, none of the current standard clinical approaches have sufficient predictive accuracies to provide definitive prognoses.ObjectiveThe objective of this study is to develop improved machine learning procedures based on EEG/ERP for determining emergence from coma.Methods and analysisData will be collected from 50 participants in coma. EEG/ERP data will be recorded for 24 consecutive hours at a maximum of five time points spanning 30 days from the date of recruitment to track participants’ progression. The study employs paradigms designed to elicit brainstem potentials, middle-latency responses, N100, mismatch negativity, P300 and N400. In the case of patient emergence, data are recorded on that occasion to form an additional basis for comparison. A relevant data set will be developed from the testing of 20 healthy controls, each spanning a 15-hour recording period in order to formulate a baseline. Collected data will be used to develop an automated procedure for analysis and detection of various ERP components that are salient to prognosis. Salient features extracted from the ERP and resting-state EEG will be identified and combined to give an accurate indicator of prognosis.Ethics and disseminationThis study is approved by the Hamilton Integrated Research Ethics Board (project number 4840). Results will be disseminated through peer-reviewed journal articles and presentations at scientific conferences.Trial registration numberNCT03826407.
Longitudinal effect of nocturnal R-R intervals changes on cardiovascular outcome in a community-based cohort
Authors: Sankari Abdulghani , Ravelo Laurel Anne , Maresh Scott , Aljundi Nawar , Alsabri Bander , Fawaz Serene , Hamdon Mulham , Al-kubaisi Ghazwan , Hagen Erika , Badr M Safwan , Peppard Paul 
Published: July 2019

RationaleSleep-disordered breathing (SDB) is strongly linked to adverse cardiovascular outcomes (cardiovascular diseases (CVD)). Whether heart rate changes measured by nocturnal R-R interval (RRI) dips (RRI dip index (RRDI)) adversely affect the CVD outcomes is unknown.ObjectivesTo test whether nocturnal RRDI predicts CVD incidence and mortality in the Wisconsin Sleep Cohort study (WSCS), independent of the known effects of SDB on beat-to-beat variability.MethodsThe study analysed electrocardiograph obtained from polysomnography study to assess the nocturnal total RRDI (the number of RRI dips divided by the total recording time) and sleep RRDI (the number of RRI dips divided by total sleep time). A composite CVD risk as a function of total and sleep RRDI was estimated by Cox proportional hazards in the WSCS.ResultsThe study sample consisted of 569 participants from the WSCS with no prior CVD at baseline were followed up for up to 15 years. Nocturnal total RRDI (10-unit change) was associated with composite CVD event(s) (HR, 1.24 per 10-unit increment in RRDI (95% CI 1.10 to 1.39), p<0.001). After adjusting for demographic factors (age 58±8 years old; 53% male; and body mass index 31±7 kg/m2), and apnoea–hypopnoea index (AHI 4%), individuals with highest total nocturnal RRDI category (≥28 vs<15 dips/hour) had a significant HR for increased incidence of CVD and mortality of 7.4(95% CI 1.97 to 27.7), p=0.003). Sleep RRDI was significantly associated with new-onset CVD event(s) (HR, 1.21 per 10-unit increment in RRDI (95% CI 1.09 to 1.35), p<0.001) which remained significant after adjusting for demographic factors, AHI 4%, hypoxemia and other comorbidities.ConclusionIncreased nocturnal RRDI predicts cardiovascular mortality and morbidity, independent of the known effects of SDB on beat-to-beat variability. The frequency of RRDI is higher in men than in women, and is significantly associated with new-onset CVD event(s) in men but not in women.
Data quality audit of a clinical quality registry: a generic framework and case study of the Australian and New Zealand Hip Fracture Registry
Authors: Tan Aidan Christopher , Armstrong Elizabeth , Close Jacqueline , Harris Ian Andrew 
Published: July 2019

ObjectivesThe value of a clinical quality registry is contingent on the quality of its data. This study aims to pilot methodology for data quality audits of the Australian and New Zealand Hip Fracture Registry, a clinical quality registry of hip fracture clinical care and secondary fracture prevention.MethodsA data quality audit was performed by independently replicating the data collection and entry process for 163 randomly selected patient records from three contributing hospitals, and then comparing the replicated data set to the registry data set. Data agreement, as a proxy indicator of data accuracy, and data completeness were assessed.ResultsAn overall data agreement of 82.3% and overall data completeness of 95.6% were found, reflecting a moderate level of data accuracy and a very high level of data completeness. Half of all data disagreements were caused by information discrepancies, a quarter by missing discrepancies and a quarter by time, date and number discrepancies. Transcription discrepancies only accounted for 1 in every 50 data disagreements. The sources of inaccurate and incomplete data have been identified with the intention of implementing data quality improvement.ConclusionsRegular audits of data abstraction are necessary to improve data quality, assure data validity and reliability and guarantee the integrity and credibility of registry outputs. A generic framework and model for data quality audits of clinical quality registries is proposed, consisting of a three-step data abstraction audit, registry coverage audit and four-step data quality improvement process. Factors to consider for data abstraction audits include: central, remote or local implementation; single-stage or multistage random sampling; absolute, proportional, combination or alternative sample size calculation; data quality indicators; regular or ad hoc frequency; and qualitative assessment.
Assessing the safety of electronic health records: a national longitudinal study of medication-related decision support
Authors: Holmgren A Jay , Co Zoe , Newmark Lisa , Danforth Melissa , Classen David , Bates David 
Published: July 2019

BackgroundElectronic health records (EHR) can improve safety via computerised physician order entry with clinical decision support, designed in part to alert providers and prevent potential adverse drug events at entry and before they reach the patient. However, early evidence suggested performance at preventing adverse drug events was mixed.MethodsWe used data from a national, longitudinal sample of 1527 hospitals in the USA from 2009 to 2016 who took a safety performance assessment test using simulated medication orders to test how well their EHR prevented medication errors with potential for patient harm. We calculated the descriptive statistics on performance on the assessment over time, by years of hospital experience with the test and across hospital characteristics. Finally, we used ordinary least squares regression to identify hospital characteristics associated with higher test performance.ResultsThe average hospital EHR system correctly prevented only 54.0% of potential adverse drug events tested on the 44-order safety performance assessment in 2009; this rose to 61.6% in 2016. Hospitals that took the assessment multiple times performed better in subsequent years than those taking the test the first time, from 55.2% in the first year of test experience to 70.3% in the eighth, suggesting efforts to participate in voluntary self-assessment and improvement may be helpful in improving medication safety performance.ConclusionHospital medication order safety performance has improved over time but is far from perfect. The specifics of EHR medication safety implementation and improvement play a key role in realising the benefits of computerising prescribing, as organisations have substantial latitude in terms of what they implement. Intentional quality improvement efforts appear to be a critical part of high safety performance and may indicate the importance of a culture of safety.
Important outcomes of moral case deliberation: a Euro-MCD field survey of healthcare professionals’ priorities
Authors: Svantesson Mia , de Snoo-Trimp Janine C , Ursin Göril , de Vet Henrica CW , Brinchmann Berit S , Molewijk Bert 
Published: July 2019

BackgroundThere is a lack of empirical research regarding the outcomes of such clinical ethics support methods as moral case deliberation (MCD). Empirical research in how healthcare professionals perceive potential outcomes is needed in order to evaluate the value and effectiveness of ethics support; and help to design future outcomes research. The aim was to use the European Moral Case Deliberation Outcome Instrument (Euro-MCD) instrument to examine the importance of various MCD outcomes, according to healthcare professionals, prior to participation.MethodsA North European field survey among healthcare professionals drawn from 73 workplaces in a variety of healthcare settings in the Netherlands, Norway and Sweden. The Euro-MCD instrument was used.ResultsAll outcomes regarding the domains of moral reflexivity, moral attitude, emotional support, collaboration, impact at organisational level and concrete results, were perceived as very or quite important by 76%–97% of the 703 respondents. Outcomes regarding collaboration and concrete results were perceived as most important. Outcomes assessed as least important were mostly about moral attitude. ‘Better interactions with patient/family’ emerged as a new domain from the qualitative analysis. Dutch respondents perceived most of the outcomes as significantly less important than the Scandinavians, especially regarding emotional support. Furthermore, men, those who were younger, and physician-respondents scored most of the outcomes as statistically significantly less important compared with the other respondents.ConclusionsThe findings indicate a need for a broad instrument such as the Euro-MCD. Outcomes related to better interactions between professionals and patients must also be included in the future. The empirical findings raise the normative question of whether outcomes that were perceived as less important, such asmoralreflexivity andmoralattitude outcomes, should still be included. In the future, a combination of empirical findings (practice) and normative reflection (theories) will contribute to the revision of the instrument.
Dermatitis among workers in Ontario: results from the Occupational Disease Surveillance System
Authors: Shakik Sharara , Arrandale Victoria , Holness Dorothy Linn , MacLeod Jill S , McLeod Christopher B , Peter Alice , Demers Paul A 
Published: July 2019

ObjectivesDermatitis is the most common occupational skin disease, and further evidence is needed regarding preventable risk factors. The Occupational Disease Surveillance System (ODSS) derived from administrative data was used to investigate dermatitis risk among industry and occupation groups in Ontario.MethodsODSS cohort members were identified from Workplace Safety and Insurance Board (WSIB) accepted lost time claims. A case was defined as having ≥2 dermatitis physician billing claims during a 12-month period within 3 years of cohort entry. A 3-year look-back period prior to cohort entry was used to exclude prevalent cases without a WSIB claim. Workers were followed for 3 years or until dermatitis diagnosis, age 65 years, emigration, death or end of follow-up (31 December 2016), whichever occurred first. Age-adjusted and sex-adjusted Cox proportional hazard models estimated HRs and 95% CIs. The risk of dermatitis was explored using a job exposure matrix that identifies exposure to asthmagens, many of which also cause contact dermatitis.ResultsAmong 597 401 workers, 23 843 cases of new-onset dermatitis were identified. Expected elevated risks were observed among several groups including furniture and fixture industries, food and beverage preparation and chemicals, petroleum, rubber, plastic and related materials processing occupations and workers exposed to metal working fluids and organic solvents. Decreased risk was observed among farmers, nurses and construction industries, and occupations exposed to latex and indoor cleaning products.ConclusionsODSS can contribute to occupational dermatitis surveillance in Ontario by identifying occupational groups at risk of dermatitis that can then be prioritised for prevention activities.
Initial management of immune thrombocytopaenia in adults based on risk stratification
Authors: Umakanthan Jaydev Manikkam , Dhakal Prajwal , Gundabolu Krishna , Kallam Avyakta , Almquist Daniel R , Bhatt Vijaya Raj 
Published: July 2019

AbstractPatients with immune thrombocytopaenia (ITP) have a wide spectrum of disease severity and bleeding risk even at similar platelet counts. Hence, additional clinical and laboratory factors may be considered in the evaluation of bleeding risk in ITP. Risk stratification based on predicted bleeding risk may help to identify high-risk patients and guide the initial management of ITP in adults requiring treatment. Recent evidence supports the use of high-dose dexamethasone therapy over prednisone in the initial management of ITP because of improved initial response rates, shorter median time to response and better safety profile. A risk-stratified approach to management of ITP is hoped to reduce bleeding complications in high-risk patients; however, the outcomes of such management approach need to be studied prospectively. Additionally, whether therapy intensification or combination of dual therapy such as intravenous immunoglobulin or rituximab in combination with dexamethasone can reduce bleeding complications in high-risk ITP should be studied in the future.
Prevalence and persistence ofChlamydia trachomatis-specific antibodies after occasional and recurrent infections
Authors: Öhman Hanna , Rantsi Tiina , Joki-Korpela Päivi , Tiitinen Aila , Surcel Heljä-Marja 
Published: July 2019

ObjectivesPopulation-basedChlamydia trachomatisseroepidemiological studies help to identify trends in chlamydia infection. However, an improved understanding of the antibody response to infection is required when using serology to estimate cumulative incidence. Thus, the objectives of this longitudinal, retrospective, biobank-based study were to assess the appearance and persistence ofC. trachomatismajor outer membrane protein (MOMP)-specific serum IgG antibodies after infection and to evaluate the role of antibodies in providing protective immunity against recurrent infection.MethodsData of notifiedC. trachomatisinfections in Finland were obtained from the National Infectious Diseases Register. Serum samples were acquired from the Finnish Maternity Cohort. 411 women with single chlamydia infection and 62 women with recurrent infections, and for whom suitable paired serum samples were available, were included in the study. Antibody appearance, persistence after infection and the impact of recurrent infections were evaluated. IgG antibodies specific for MOMP were measured from serum using an ELISA method.ResultsAnti-C. trachomatisMOMP-specific IgG antibodies were detected in 65.5% (269/411) of women within 3 months of notification of infection. In the absence of recurrent infection, seroprevalence declined to 34.5% (142/411) 3–10 years after the initial infection. The serum antibody levels at baseline correlated positively with seroprevalence at follow-up. Reinfection boosted the humoral immune response by increasing seroprevalence and the serum antibody levels. Seroprevalence within 3 months after first notification of infection was 65.5% (19/29) in women who were later diagnosed with recurrent infection, comparable with women with single notification of infection (65.5%, 269/411).ConclusionsApproximately one-third of women with single notification of chlamydia infection remain seropositive 3–10 years after the initial infection. The concentration of antibodies remained stable during the follow-up. Recurrent infection boosted the humoral immune response, but reinfection occurred despite the presence of pre-existing antibodies.
Chronic cannabis use and circulating biomarkers of neural health, stress, and inflammation in physically active individuals
Authors: Lisano Jonathon K. , Kisiolek Jacob N. , Smoak Peter , Phillips Kristina T. , Stewart Laura K. 
Published: July 2019

Previous research has associated cannabis use with altered circulating neurotrophins and biomarkers of immune health, but these relationships have yet to be fully explored in physically active individuals. The specific aim of this study was to explore the relationships between biomarkers of neural health: nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), immune health: interleukin 6 (IL-6), C-reactive protein (CRP), and cortisol, as well as the presence of depression, in physically active cannabis users (CU) and nonusers (NU). Male and female participants (N = 30; CU, n = 15, NU, n = 15) provided intravenous blood samples and underwent assessment of body composition, maximal oxygen consumption, and depression (Beck Depression Inventory-II (BDI-II)). Samples were analyzed for concentrations of NGF, BDNF, IL-6, CRP, and cortisol using ELISAs. CU and NU were compared using an unpaired t test. Pearson’s correlation and multiple linear regression were used to evaluate relationships among variables. There were no significant differences in body size or composition, maximal oxygen consumption, total BDI-II Score, concentrations of NGF, IL-6, CRP, or cortisol between groups. BDNF was significantly lower in CU compared with NU (p = 0.02), with a significant negative relationship between BDNF and CRP (p = 0.02). Mean concentrations of CRP placed CU at higher risk for cardiovascular disease compared with NU. Total BDI-II score negatively correlated with BDNF (p = 0.02) and positively correlated with CRP (p = 0.02).Novelty Plasma BDNF was significantly lower in physically active cannabis users compared with NU. CU were classified at moderate risk for cardiovascular disease based on average circulating CRP compared with low risk for NU.