bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in colloid solution sales in Nordic countries
Authors: Kongsgaard U. E. , Holtan A. , Perner A.
Published: January 2018

Background

Administration of resuscitation fluid is a common intervention in the treatment of critically ill patients, but the right choice of fluid is still a matter of debate. Changes in medical practice are based on new evidence and guidelines as well as traditions and personal preferences. Official warnings against the use of hydroxyl‐ethyl‐starch (HES) solutions have been issued. Nordic guidelines have issued several strong recommendations favouring crystalloids over colloids in all patient groups. Our objective was to describe the patterns of colloid use in Nordic countries from 2012 to 2016.

Methods

The data were obtained from companies that provide pharmaceutical statistics in different countries. The data are sales figures from pharmaceutical companies to pharmacies and health institutions.

Results

We found a 56% reduction in the total sales of all colloids in Nordic countries over a 5‐year period. These findings were mainly related to a 92% reduction in the sales of HES solutions. A reduction in sales of other synthetic colloids has also occurred. During the same period, we found a 46% increase in albumin sales, but these numbers varied between Nordic countries.

Conclusion

The general reduction in colloid sales likely reflects the recommendation that colloids should be used only in special circumstances. The dramatic reduction in the sales of HES solutions was expected given evidence of harm and the official warnings. The steady increase in albumin sales and the notable differences between the five Nordic countries cannot be explained.
Pre‐hospital emergency anaesthesia in awake hypotensive trauma patients: beneficial or detrimental?
Authors: Crewdson K. , Rehn M. , Brohi K. , Lockey D. J.
Published: January 2018

Background

The benefits of pre‐hospital emergency anaesthesia (PHEA) are controversial. Patients who are hypovolaemic prior to induction of anaesthesia are at risk of severe cardiovascular instability post‐induction.

This study compared mortality for hypovolaemic trauma patients (without major neurological injury) undergoing PHEA with a patient cohort with similar physiology transported to hospital without PHEA.

Methods

A retrospective database review was performed to identify patients who were hypotensive on scene [systolic blood pressure (SBP) < 90 mmHg], and GCS 13–15. Patient records were reviewed independently by two pre‐hospital clinicians to identify the likelihood of hypovolaemia. Primary outcome measure was mortality defined as death before hospital discharge.

Results

Two hundred and thirty‐six patients were included; 101 patients underwent PHEA. Fifteen PHEA patients died (14.9%) compared with six non‐PHEA patients (4.4%), P = 0.01; unadjusted OR for death was 3.73 (1.30–12.21; P = 0.01). This association remained after adjustment for age, injury mechanism, heart rate and hypovolaemia (adjusted odds ratio 3.07 (1.03–9.14) P = 0.04).

Fifty‐eight PHEA patients (57.4%) were hypovolaemic prior to induction of anaesthesia, 14 died (24%). Of 43 PHEA patients (42.6%) not meeting hypovolaemia criteria, one died (2%); unadjusted OR for mortality was 13.12 (1.84–578.21). After adjustment for age, injury mechanism and initial heart rate, the odds ratio for mortality remained significant at 9.99 (1.69–58.98); P = 0.01.

Conclusion

Our results suggest an association between PHEA and in‐hospital mortality in awake hypotensive trauma patients, which is strengthened when hypotension is due to hypovolaemia. If patients are hypovolaemic and awake on scene it might, where possible, be appropriate to delay induction of anaesthesia until hospital arrival.
Good quality of life before cardiac arrest predicts good quality of life after resuscitation
Authors: Hellevuo H. , Sainio M. , Huhtala H. , Olkkola K. T. , Tenhunen J. , Hoppu S.
Published: January 2018

Background

The survival rate of cardiac arrest patients is increasing. Our aim was to compare the quality of life before and after cardiac arrest and analyse the factors associated with outcome.

Methods

All adult cardiac arrest patients admitted to the Tampere University Hospital intensive care unit between 2009 and 2011 were included in a retrospective follow‐up study if surviving to discharge and were asked to return a questionnaire after 6 months. Data on patient demographics and pre‐arrest quality of life were retrieved from medical records. Data are given as means (SD) or medians [Q1, Q3]. We used logistic regression to identify factors associated with better quality of life after cardiac arrest.

Results

Six months after cardiac arrest, 36% (79/222) were alive and 70% (55/79) of those patients completed the follow‐up EuroQoL (EQ‐5D) quality of life questionnaire. Median values for the EQ‐5D before and after cardiac arrest were 0.89 [0.63, 1] and 0.89 [0.62, 1], respectively (P = 0.75). Only the EQ‐5D prior to cardiac arrest was associated with better quality of life afterwards (OR 1.2; 95% CI 1.0–1.3; P = 0.02).

Conclusions

Quality of life remained good after cardiac arrest especially in those patients who had good quality of life before cardiac arrest.
Validation of a behavioral economic purchase task for assessing drug abuse liability
Authors: MacKillop James , Goldenson Nicholas I. , Kirkpatrick Matthew G. , Leventhal Adam M.
Published: January 2018

Behavioral economic purchase tasks quantify drug demand (i.e. reinforcing value of a drug) and have been used extensively to assess the value of various drugs among current users. However, purchase tasks have been rarely used with unfamiliar drugs to address a compound's abuse liability, and the current study sought to validate the paradigm in this capacity. Using a double‐blind placebo‐controlled within‐subjects drug challenge design, the study evaluated differential drug demand on an experimental drug purchase task for a 20 mg dose of oral D‐amphetamine (versus placebo), a prototypic psychostimulant, in 98 stimulant‐naïve participants. Compared with placebo, amphetamine significantly increased intensity, breakpoint and Omax, and significantly decreased elasticity. Mechanistic analyses revealed that Omax and breakpoint mediated the relationship between subjective drug effects and ‘willingness to take again’, a putative indicator of liability via motivation for future drug‐seeking behavior. These findings validate the purchase task paradigm for quantifying the reinforcing value and, in turn, abuse liability of unfamiliar compounds, providing a foundation for a variety of future applications.
Cocaine conditioned place preference: unexpected suppression of preference due to testing combined with strong conditioning
Authors: Marion‐Poll Lucile , Besnard Antoine , Longueville Sophie , Valjent Emmanuel , Engmann Olivia , Caboche Jocelyne , Hervé Denis , Girault Jean‐Antoine
Published: January 2018

Conditioned place preference (CPP) is widely used for evaluating the rewarding effects of drugs. Like other memories, CPP is proposed to undergo reconsolidation during which it is unstable and sensitive to pharmacological inhibition. Previous studies have shown that cocaine CPP can be apparently erased by extracellular signal‐regulated kinase (ERK) pathway inhibition during cocaine reconditioning (re‐exposure to the drug‐paired environment in the presence of the drug). Here, we show that blockade of D1 receptors during reconditioning prevented ERK activation and induced a loss of CPP. However, we also unexpectedly observed a CPP disappearance in mice that underwent testing and reconditioning with cocaine alone, specifically in strong conditioning conditions. The loss was due to the intermediate test. CPP was not recovered with reconditioning or priming in the short term, but it spontaneously reappeared after a month. When we challenged the D1 antagonist‐mediated erasure, we observed that both a high dose of cocaine and a first CPP test were required for this effect. Our results also suggest a balance between D1‐dependent ERK pathway activation and an A2a‐dependent mechanism in D2 striatal neurons in controlling CPP expression. Our data reveal that, paradoxically, a simple CPP test can induce a complete (but transient) loss of place preference following strong but not weak cocaine conditioning. This study emphasizes the complex nature of CPP memory and the importance of multiple parameters that must be taken into consideration when investigating reconsolidation.
Trends in alcohol‐related mortality in East and West Germany, 1980–2014: age, period and cohort variations
Authors: Piontek Daniela , Kraus Ludwig
Published: January 2018

Background and aims

Several indicators suggest that the extent and trends of alcohol‐related mortality differ between East and West Germany. Regional drinking patterns and differences in health‐care systems are assumed to affect the risk of dying from an alcohol‐induced disease. The study addresses two questions: (1) what are the unbiased and independent age, period and cohort effects on alcohol‐related mortality trends in Germany; and (2) do these trends differ between East and West Germany?

Methods

Data on alcohol‐related mortality for East and West Germany came from the national causes of death register for the years 1980–2014. Analyses included all deaths fully attributable to alcohol based on the International Classification of Diseases (ICD‐9 and ICD‐10). Gender‐stratified age–period–cohort analyses were conducted using the intrinsic estimator model.

Results

Age effects showed a concave pattern with a peak at ages 55–64 years in both regions. Incidence rate ratios (IRR) in East Germany were highest in the years 1990–1994 (men and women: IRR = 1.52) and declined thereafter. In West Germany, IRR were lowest in 1980–1984 (men: IRR = 0.81, women: IRR = 0.75) and stabilized at approximately 1.10 since 1995–1999. Cohort effects showed continuously lower IRR for those born after 1955–1959 in the East and those born after 1945–1949 in the West. Patterns for males and females were comparable.

Conclusions

The results suggest that alcohol‐related mortality showed different trends in East and West Germany, which can be explained partly by different drinking patterns before and changes in the health‐care system after the reunification.
“A New Hope for Asia”? Australia, the United States and the Promotion of Economic Development in Southeast Asia
Authors: Ferns Nicholas
Published: January 2018

The Colombo Plan and Point Four program were programs that provided technical and economic assistance to the newly independent countries of Southeast Asia. They represented Commonwealth and American attempts to promote economic development in the region. This paper will investigate how these policies, which were framed by US policy‐makers and academics, were adopted in Australia. In so doing, it will demonstrate the ways that development was perceived as an important consideration in the foreign policies of both Australia and the United States. It will also examine the place of these programs in the Cold War and postcolonial world of the 1950s. As this paper will show, the interaction of these factors would affect Australian foreign policy for decades to come, revealing much about the complex nature of the Australian‐American relationship.
IL‐37 inhibits IL‐4/IL‐13‐induced CCL11 production and lung eosinophilia in murine allergic asthma
Authors: Lv J. , Xiong Y. , Li W. , Cui X. , Cheng X. , Leng Q. , He R.
Published: January 2018

Background

IL‐37 is emerging as an anti‐inflammatory cytokine, particularly in innate inflammation. However, the role of IL‐37 in Th2‐mediated allergic lung inflammation remains uncertain. We sought to determine the role and the underlying mechanisms of IL‐37 in the development of house dust mites (HDM)‐induced murine asthma model.

Methods

We examined the effect of IL‐37 administration during the sensitization or challenge phase on Th2‐mediated allergic asthma induced by inhaled HDM. Cellular source of CCL11 and distribution of IL‐37 receptors, IL‐18Rα and IL‐1R8, were determined in HDM‐exposed lungs. Finally, we examined the effect of IL‐37 on CCL11 production and STAT6 activation in different primary lung structural cell types upon IL‐4/IL‐13 stimulation.

Results

IL‐37 had no effect on HDM sensitization, but when administrated during the challenge phase, significantly attenuated pulmonary eosinophilia, CCL11 production, and airway hyper‐reactivity (AHR). Interestingly, IL‐37 treatment had no significant effects on lung infiltrating T cells and Th2 cytokine production. Intranasal co‐administration of CCL11 reversed the inhibiting effect of IL‐37 on HDM‐induced pulmonary eosinophilia and AHR. Furthermore, we demonstrated that CCL11 was primarily expressed by fibroblasts and airway smooth muscle cells (AMSC), while IL‐37 receptors by tracheobronchial epithelial cells (TEC). In vitro study showed that IL‐37 inhibited IL‐4/IL‐13‐induced STAT6 activation and CCL11 production by fibroblasts and AMSC, which was dependent on its direct action on TEC. Moreover, cell contact was required for the inhibitory effect of IL‐37‐treated TEC.

Conclusions

IL‐37 attenuates HDM‐induced asthma, possibly by inhibiting IL‐4/IL‐13‐induced CCL11 production by fibroblasts and AMSC via its direct act on TEC.
Diagnostic accuracy, risk assessment, and cost‐effectiveness of component‐resolved diagnostics for food allergy: A systematic review
Authors: Flores Kim J. , McCleary N. , Nwaru B. I. , Stoddart A. , Sheikh A.
Published: January 2018

Background

Component‐resolved diagnostics (CRD) are promising tools for diagnosing food allergy, offering the potential to determine specific phenotypes and to develop patient‐tailored risk profiles. Nevertheless, the diagnostic accuracy of these tests varies across studies; thus, their clinical utility remains unclear. Therefore, we synthesized the evidence from studies investigating the diagnostic accuracy, risk assessment ability, and cost‐effectiveness of CRD for food allergy.

Methods

We systematically searched 10 electronic databases and four clinical trial registries for studies published from January 2000 to February 2017. The quality of included studies was assessed using QUADAS‐2. Due to heterogeneity, we narratively synthesized the evidence.

Results

Eleven studies met inclusion criteria, altogether recruiting 1098 participants. The food allergies investigated were cow's milk, hen's egg, peanut, hazelnut, and shrimp. The components with the highest diagnostic accuracy for each allergen, along with their sensitivity‐specificity pairs, were as follows: Bos d 4 for cow's milk (62.0% and 87.5%), Gal d 1 for hen's egg (84.2% and 89.8% for heated egg, and 60.6% and 97.1% for raw egg), Ara h 6 for peanut (94.9% and 95.1%), Cor a 14 for hazelnut (100% and 93.8%), and Lit v 1 for shrimp (82.8% and 56.3%) allergy.

Conclusion

Selected components of cow's milk, hen's egg, peanut, hazelnut, and shrimp allergen showed high specificity, but lower sensitivity. However, few studies exist for each component, and studies vary widely regarding the cutoff values used, making it challenging to synthesize findings across studies. Further research is needed to determine clinically appropriate cutoff values, risk assessment abilities, and cost‐effectiveness of CRD approaches.
Systemic IL‐2/anti‐IL‐2Ab complex combined with sublingual immunotherapy suppresses experimental food allergy in mice through induction of mucosal regulatory T cells
Authors: Smaldini P. L. , Trejo F. , Cohen J. L. , Piaggio E. , Docena G. H.
Published: January 2018

Background

Therapeutic tolerance restoration has been proven to modify food allergy in patients and animal models and although sublingual immunotherapy (SLIT) has showed promise, combined therapy may be necessary to achieve a strong and long‐term tolerance.

Aims

In this work, we combined SLIT with systemic administration of IL‐2 associated with an anti‐IL‐2 monoclonal antibody (IL‐2/anti‐IL‐2Ab complex or IL‐2C) to reverse the IgE‐mediated experimental allergy.

Materials and Methods

Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged with allergen to elicit hypersensitivity reactions. Then, allergic mice were treated with a sublingual administration of very low amounts of milk proteins combined with intraperitoneal injection of low doses of IL‐2C. The animals were next re‐exposed to allergens and mucosal as well as systemic immunological parameters were assessed in vivo and in vitro.

Results

The treatment reduced serum specific IgE, IL‐5 secretion by spleen cells and increased IL‐10 and TGF‐β in the lamina propria of buccal and duodenal mucosa. We found an augmented frequency of IL‐10‐secreting CD4+CD25+Foxp3+ regulatory T cells (Treg) in the submaxilar lymph nodes and buccal lamina propria. Tregs were sorted, characterized and adoptively transferred to naïve mice, which were subsequently sensitized. No allergy was experienced in these mice and we encouragingly discovered a faster and more efficient tolerance induction with the combined therapy compared with SLIT.

Conclusion

The combination of two therapeutic strategies rendered Treg‐mediated tolerance more efficient compared to individual treatments and reversed the established IgE‐mediated food allergy. This approach highlights the ability of IL‐2C to expand Tregs, and it may represent a promising disease‐modifying therapy for managing food allergy.
Usefulness of asthma predictive index in ascertaining asthma status of children using medical records: An explorative study
Authors: Wi C.‐I. , Krusemark E. A. , Voge G. , Sohn S. , Liu H. , Ryu E. , Park M. A. , Castro‐Rodriguez J. A. , Juhn Y. J.
Published: January 2018

Background

Frequent wheezing in original asthma predictive index (API) was defined by parental report of recurrent wheezing within 1 year during the first 3 years of life. The nature of frequent wheezing in children, particularly aged over 3 years, has not been studied. We aimed to assess the frequency and interval of wheezing to define frequent wheezing in ascertaining asthma for children using medical records.

Methods

Among children who participated in a previous study (n = 427), all wheezing episodes documented in medical records were collected for children who had ≥2 wheezing episodes PLUS met one major criterion or two minor criteria of API. We compared the distribution of known risk factors for asthma between subjects having two consecutive wheezing episodes with shorter interval (≤1 year) compared to those with longer interval (1 to 3 years).

Results

A total of 62 children met API at median age of 2.3 years. During follow‐up period (median age: 11.3 years), a total of 198 wheezing episodes were observed. 81% of wheezing intervals were within 3 years from the earlier wheezing episode, including 60% within 1 year. Children who met API based on 1‐year interval (n = 40) vs 1‐ to 3‐year interval (n = 13) appeared to be similar in regard to the known risk factors for asthma.

Conclusions

Our exploratory study finding suggests that children who had frequent wheezing episodes with longer interval (<3 years) need to be considered to be determined as asthma cases when API is applied to retrospective medical records. Prospective studies with a larger sample size need to replicate this finding.
A before‐and‐after observational study of a protocol for use of the C‐MAC videolaryngoscope with a Frova introducer in pre‐hospital rapid sequence intubation
Authors: Ångerman S. , Kirves H. , Nurmi J.
Published: January 2018

Results using videolaryngoscopy in pre‐hospital rapid sequence intubation are mixed. A bougie is not commonly used with videolaryngoscopy. We hypothesised that using videolaryngoscopy and a bougie as core elements of a standardised protocol that includes a drugs and a laryngoscopy algorithm would result in a high first‐pass tracheal intubation success rate. We employed videolaryngoscopy (C‐MAC) combined with a bougie (Frova intubating introducer) in an anaesthetist‐staffed helicopter emergency medical service. Data for adult tracheal intubation were collected prospectively as part of the airway registry of our unit for 22 months after implementation of the protocol (n = 543) and compared with controls (n = 238) treated in the previous year before the implementation. The mean first‐pass success rate (95%CI) was 98.2% (96.6–99.0%) in the study group and 85.7% (80.7–89.6%) in the control group, p < 0.0001. Combining C‐MAC videolaryngoscopy and bougie with a standardised rapid sequence induction protocol leads to a high first attempt intubation success rate when performed by an anaesthetist‐led helicopter emergency medical service team.
Solid pseudopapillary tumour of the pancreas: clinicopathological analysis
Authors: McCluney Simon , Wijesuriya Nilukshi , Sheshappanavar Vinayata , Chin‐Aleong Joanne , Feakins Roger , Hutchins Robert , Abraham Ajit , Bhattacharya Satyajit , Valente Roberto , Kocher Hemant
Published: January 2018

Background

We report on our experience of the surgical management and outcomes of 11 patients with solid pseudopapillary tumour of the pancreas (SPT). We sought to correlate the immunohistochemical staining of these tumours with that previously reported in the literature.

Methods

A retrospective analysis of the clinical presentation, radiological findings, surgical treatment, histopathological characteristics and outcomes for patients surgically managed with SPT at The Royal London Hospital. A literature search was performed to analyse the immunohistochemical stains commonly used to diagnose SPT.

Results

Between August 2006 and April 2016, 10 females and one male patient underwent surgery for SPT. The localization of the tumour was in the pancreatic head in two patients, one in the neck, three in the body and five in the tail. All 11 patients had localised disease. Six patients suffered post‐surgical complications. Histopathology shows immunoreactivity for: β‐catenin, vimentin, CD‐10, CD‐56, α1‐antitrypsin and negative staining for synaptophysin and chromogranin. At a median of 24 months of follow‐up, the disease‐free survival rate was 100% and no recurrence was noted. A literature review generated 38 suitable articles with 116 individual cases of SPT, with high expression of vimentin and neuron specific enolase throughout, and low rates of chromogranin and synatophysin positivity.

Conclusion

SPT is rare and affects mostly young women. An accurate diagnosis is important as the relative indolent behaviour can be managed with surgical resection even when large in size, bringing excellent long‐term outcomes.
Which outcome measures should be used in stress urinary incontinence trials?
Authors: Lim Renly , Liong Men Long , Leong Wing Seng , Yuen Kah Hay
Published: January 2018

Objective

To review measures used in recent randomised controlled trials (RCTs) evaluating stress urinary incontinence (SUI) treatments and to propose the most relevant outcome measure that should be included in future trials.

Materials and methods

We identified RCTs for SUI interventions published between January 2015 and July 2017. We listed the objective and subjective outcome measures used in eligible trials in the literature search. Using data from our RCT conducted from 2013 to 2016 evaluating pulsed magnetic stimulation for SUI, we analysed the correlation between all measures.

Results

A total of 45 RCTs were included; 28 (62%) involved surgical interventions. The most frequently used objective and subjective measures were the cough stress test and International Consultation on Incontinence Questionnaire‐Urinary Incontinence Short Form (ICIQ‐UI SF), respectively. In all, 24 different validated questionnaires were administered in the 42 studies that used subjective outcome measure. Analyses of measures used in our trial showed that all measures were significantly correlated with each other except for pelvic floor muscle function. The ICIQ‐UI SF showed the highest correlation coefficients (0.587–0.733) with all outcome measures.

Conclusion

The outcome measures used in recent trials were inconsistent. The ICIQ‐UI SF had the highest correlation with all measures in our trial; however, further studies evaluating correlation of measures in other patient cohorts are needed to corroborate our present results. We propose the use of ICIQ‐UI SF, as the most relevant outcome measure, in future trials evaluating efficacy of SUI interventions.
Low‐dose‐rate brachytherapy for prostate cancer: outcomes at >10 years of follow‐up
Authors: Lazarev Stanislav , Thompson Marcher R. , Stone Nelson N. , Stock Richard G.
Published: January 2018

Objective

To examine biochemical control, survival, and late morbidity with definitive low‐dose‐rate brachytherapy (LDR‐BT) for patients with prostate cancer surviving for >10 years after treatment.

Patients and Methods

We identified 757 men with localised prostate cancer who underwent definitive LDR‐BT in the period 1990–2006 and were followed for >10 years at our institution. Biochemical failure‐free survival (BFFS), distant metastases‐free survival (DMFS), prostate cancer‐specific survival (PCSS), and overall survival (OS) were selected as study endpoints. Survival was examined using the log‐rank test, Kaplan–Meier method, and Cox regression modelling. Urinary, quality of life (QoL), and potency scores at baseline and last follow‐up were recorded.

Results

The median follow‐up was 12.5 years (range, 10.1–21.8 years). At the time of analysis, 88.6% of patients were alive, 1.5% died from prostate cancer and 13.9% developed biochemical failure, with 82% of failures occurring in the first decade of follow‐up. Overall, 2.3% developed distant metastases. On multivariate analyses, stage T3a–T3b, prostate‐specific antigen level of >20 ng/mL, intermediate‐ and high‐risk disease predicted worse BFFS; whereas age >70 years at diagnosis and stage T3a–T3b predicted worse OS. A total biologically effective dose of ≥150 Gy and androgen‐deprivation therapy were associated with improved BFFS, but not OS. The overall 17‐year rates for BFFS, DMFS, PCSS, and OS were 79, 97, 97, and 72%, respectively. Respective 17‐year BFFS rates for low‐, intermediate‐ and high‐risk patients were 86, 80, and 65% (P < 0.001), whereas OS rates for the same groups were 82, 73, and 60%, respectively (P = 0.09). Amongst those patients who were potent at baseline, 25% remained potent at the last follow‐up. Urinary function and QoL were mainly unaffected.

Conclusions

LDR‐BT yields excellent survival rates, with a 17‐year PCSS rate of 97%. In all, 18% of patients with biochemical relapse failed at >10 years after implantation, which justifies their continued follow‐up.
The effect of timing of an immediate instillation of mitomycin C after transurethral resection in 941 patients with non‐muscle‐invasive bladder cancer
Authors: Bosschieter Judith , van Moorselaar R. Jeroen A. , Vis André N. , van Ginkel Tessa , Lissenberg‐Witte Birgit I. , Beckers Goedele M.A. , Nieuwenhuijzen Jakko A.
Published: January 2018

Objective

To investigate whether the timing of an immediate instillation of mitomycin C (on the day of transurethral resection of bladder tumour [TURBT] or 1 day later) has an impact on time to recurrence of non‐muscle‐invasive bladder cancer (NMIBC).

Patients and Methods

All patients with NMIBC who were enrolled in a prospective trial between 1998 and 2003, and treated with an early mitomycin C instillation (on the day of TURBT or 1 day later), were selected. Statistical analysis was performed with Kaplan–Meier curves and multivariable Cox regression.

Results

Administering an instillation of mitomycin C on the day of TURBT or 1 day later did not show a statistically significant difference in time to recurrence in a univariable model (log‐rank P = 0.99). After correcting for the number of scheduled adjuvant instillations, no statistically significant difference could be detected either: hazard ratio 1.05 (95% confidence interval 0.81–1.35, P = 0.74).

Conclusion

These data do not support the hypothesis that a very early instillation (on the day of TURBT) of mitomycin C decreases the risk of recurrence as compared with an early instillation (1 day after TURBT).
Extension of caution indices to mixed‐format tests
Authors: Sinharay Sandip
Published: January 2018

Tatsuoka suggested several extended caution indices and their standardized versions, and these have been used as person‐fit statistics by various researchers. However, these indices are only defined for tests with dichotomous items. This paper extends two of the popular standardized extended caution indices for use with polytomous items and mixed‐format tests. Two additional new person‐fit statistics are obtained by applying the asymptotic standardization of person‐fit statistics for mixed‐format tests. Detailed simulations are then performed to compute the Type I error rate and power of the four new person‐fit statistics. Two real data illustrations follow. The new person‐fit statistics appear to be satisfactory tools for assessing person fit for polytomous items and mixed‐format tests.
Oral diseases associated with condition‐specific oral health‐related quality of life and school performance of Thai primary school children: A hierarchical approach
Authors: Kaewkamnerdpong Issarapong , Krisdapong Sudaduang
Published: January 2018

Objectives

To assess the hierarchical associations between children's school performance and condition‐specific (CS) oral health‐related quality of life (OHRQoL), school absence, oral status, sociodemographic and economic status (SDES) and social capital; and to investigate the associations between CS OHRQoL and related oral status, adjusting for SDES and social capital.

Methods

Data on 925 sixth grade children in Sakaeo province, Thailand, were collected through oral examinations for dental caries and oral hygiene, social capital questionnaires, OHRQoL interviews using the Child‐Oral Impacts on Daily Performances index, parental self‐administered questionnaires and school documents. A hierarchical conceptual framework was developed, and independent variables were hierarchically entered into multiple logistic models for CS OHRQoL and linear regression models for school performance.

Results

After adjusting for SDES and social capital, children with high DMFT or DT scores were significantly threefold more likely to have CS impacts attributed to dental caries. However, poor oral hygiene was not significantly associated with CS impacts attributed to gingival disease. High DMFT scores were significantly associated with lower school performance, whereas high Simplified Oral Hygiene Index scores were not. The final model showed that CS impacts attributed to dental caries and school absence accounted for the association between DMFT score and school performance.

Conclusions

Dental caries was associated with CS impacts on OHRQoL, and exerted its effect on school performance through the CS impacts and school absence. There was no association between oral hygiene and CS impacts on OHRQoL or school performance.
New and emerging drug treatments for severe asthma
Authors: Diver S. , Russell R. J. , Brightling C. E.
Published: January 2018

Asthma is a common chronic inflammatory condition of the airways affecting over 300 million people world‐wide. In 5%‐10% of cases, it is severe, with disproportionate healthcare resource utilization including costs associated with frequent exacerbations and the long‐term health effects of systemic steroids. Characterization of inflammatory pathways in severe asthma has led to the development of targeted biological and small molecule therapies which aim to achieve disease control while minimizing corticosteroid‐associated morbidity. Herein, we review currently licensed agents and those in development, and speculate how drug therapy for severe asthma might evolve and impact on clinical outcomes in the near future.
Quantitative and Qualitative Analysis of the Perception of Semi‐Transparent Structures in Direct Volume Rendering
Authors: Englund R. , Ropinski T.
Published: January 2018

Direct Volume Rendering (DVR) provides the possibility to visualize volumetric data sets as they occur in many scientific disciplines. With DVR semi‐transparency is facilitated to convey the complexity of the data. Unfortunately, semi‐transparency introduces challenges in spatial comprehension of the data, as the ambiguities inherent to semi‐transparent representations affect spatial comprehension. Accordingly, many techniques have been introduced to enhance the spatial comprehension of DVR images. In this paper, we present our findings obtained from two evaluations investigating the perception of semi‐transparent structures from volume rendered images. We have conducted a user evaluation in which we have compared standard DVR with five techniques previously proposed to enhance the spatial comprehension of DVR images. In this study, we investigated the perceptual performance of these techniques and have compared them against each other in a large‐scale quantitative user study with 300 participants. Each participant completed micro‐tasks designed such that the aggregated feedback gives insight on how well these techniques aid the user to perceive depth and shape of objects. To further clarify the findings, we conducted a qualitative evaluation in which we interviewed three experienced visualization researchers, in order to find out if we can identify the benefits and shortcomings of the individual techniques.
Using the Theory of Planned Behaviour to Understand Motivation to Register Births in Lombok, Indonesia
Authors: Williams Anaise , Kusumaningrum Santi , Bennouna Cyril , Usman Rahmadi , Wandasari Wenny , Stark Lindsay
Published: January 2018

Despite government interest in promoting birth registration, more than a third of Indonesian children do not have a birth certificate, affecting the realisation of both their human and citizen rights. While barriers to registering children's births in Indonesia have been assessed, there is limited research on how communities perceive the importance of having a birth certificate. This study used focus group discussions to explore parental motivations around birth registration. The results of a thematic analysis found that perceived use of birth certificates, perceived control over the application process and social norms related to certificate ownership affect the intention to apply.
Anastomotic leakage after side‐to‐end anastomosis for rectal cancer: does leakage location matter?
Authors: Hain E. , Maggiori L. , Zappa M. , Prost à la Denise J. , Panis Y.
Published: January 2018

Aim

The aim was to assess outcome according to the location of anastomotic leakage (AL) after side‐to‐end stapler or manual low colorectal or coloanal anastomosis following laparoscopic total mesorectal excision (TME) for rectal cancer.

Methods

All patients presenting with symptomatic or asymptomatic AL after TME and side‐to‐end low anastomosis for rectal cancer performed from 2005 to 2014 were identified from our prospective database. CT scans with contrast enema were reviewed to assess the location of AL origin.

Results

Among 279 patients who underwent TME with side‐to‐end anastomosis from 2005 to 2014, 70 patients presented with AL and were included: 43 (61%) patients with AL on the circular anastomosis (CAL) were compared to 27 (39%) with AL on the transverse stapling line of the colonic stump (TAL). CAL and TAL were associated with similar rates of symptomatic AL (63% vs 48%, respectively; P = 0.339), severe postoperative morbidity rates (33% vs 18%; P = 0.313) and long‐term outcomes, including definitive stoma rate (10% vs 11%; P = 0.622) and major low anterior resection syndrome rate (56% vs 57%; P = 0.961).

Conclusion

Our study showed that whatever the location of AL on a side‐to‐end low colorectal or coloanal anastomosis after TME for cancer, both short‐ and long‐term outcomes are similar.
Reduced stroke distance of the left ventricular outflow tract is independently associated with long‐term mortality, in patients hospitalized due to heart failure
Authors: Zhong You , Almodares Qays , Yang JieFu , Wang Fang , Fu Michael , Johansson Magnus C.
Published: January 2018

Purpose

Reduced blood circulation is an important feature of heart failure, and Doppler stroke distance of the left ventricular outflow tract is a measure of forward stroke volume. Several echocardiographic parameters have known prognostic implications in heart failure, but the prognostic implications of stroke distance in relation to other parameters are insufficiently known. The aim was therefore to test the hypothesis that stroke distance is associated with five‐year all‐cause mortality, independently of other echocardiography variables, and that stroke distance has added long‐term prognostic value.

Methods

A cohort of 350 consecutive elderly patients, over 65 years of age and mean 79·9 ± 7·1 years, hospitalized due to heart failure was studied. Patients with available echocardiography were included and images evaluated. Stroke distance was measured by tracing the systolic velocity time integral (VTI) of the pulsed wave Doppler in the left ventricular outflow tract. Other parameters were also estimated, such as left ventricular ejection fraction (LVEF), left ventricular mass, left atrial volume, early diastolic mitral velocity (E), deceleration time and mitral annulus tissue Doppler diastolic velocity (e′) and pulmonary artery systolic pressure (PASP).

Results

Five‐year all‐cause mortality, assessed without missing data, was 67·7%. Multivariate analysis showed that stroke distance, E/e′ and PASP were independently associated with mortality, but LVEF was not.

Conclusions

Stroke distance was associated with long‐term mortality, independently of other known echocardiographic prognostic factors in elderly patients hospitalized with heart failure. Only when stroke distance was excluded from analysis, LVEF became associated with mortality. Stroke distance had additive prognostic value.
Oroxylin A inhibits ethanol‐induced hepatocyte senescence via YAP pathway
Authors: Jin Huanhuan , Lian Naqi , Bian Mianli , Zhang Chenxi , Chen Xingran , Shao Jiangjuan , Wu Li , Chen Anping , Guo Qinglong , Zhang Feng , Zheng Shizhong
Published: January 2018

Objectives

Oroxylin A, a natural flavonoid isolated from Scutellaria baicalensis, has been reported to have anti‐hepatic injury effects. However, the effects of oroxylin A on alcoholic liver disease (ALD) remains unclear. The aim of this study was to elucidate the effects of oroxylin A on ALD and the potential mechanisms.

Materials and methods

Male ICR mice and human hepatocyte cell line LO2 were used. Yes‐associated protein (YAP) overexpression and knockdown were achieved using plasmid and siRNA technique. Cellular senescence was assessed by analyses of the senescence‐associated β‐galactosidase (SA‐β‐gal), senescence marker p16, p21, Hmga1, cell cycle and telomerase activity.

Results

Oroxylin A alleviated ethanol‐induced hepatocyte damage by suppressing activities of supernatant marker enzymes. We found that oroxylin A inhibited ethanol‐induced hepatocyte senescence by decreasing the number of SA‐β‐gal‐positive LO2 cells and reducing the expression of senescence markers p16, p21 and Hmga1 in vitro. Moreover, oroxylin A affected the cell cycle and telomerase activity. Of importance, we revealed that YAP pharmacological inhibitor verteporfin or YAP siRNA eliminated the effect of oroxylin A on ethanol‐induced hepatocyte senescence in vitro, and this was further supported by the evidence in vivo experiments.

Conclusion

Therefore, these aggregated data suggested that oroxylin A relieved alcoholic liver injury possibly by inhibiting the senescence of hepatocyte, which was dependent on its activation of YAP in hepatocytes.
Liver transplantation vs liver resection in patients with HBV‐related hepatocellular carcinoma beyond Milan criterion: A meta‐analysis
Authors: Li Wei , Li Long , Han Jun , Wu Hong
Published: January 2018

Objective

The aim of this study was to conduct a meta‐analysis of published reports to compare long‐term outcomes after liver transplantation (LT) and liver resection (LR), respectively, in patients with HBV‐related hepatocellular carcinoma (HCC) beyond the Milan criterion.

Methods

A systematic search of the Embase, Medline, PubMed databases, and the Cochrane Library was performed using both medical subject headings (MeSH) and truncated word searches to identify all comparative studies published on this topic. The primary outcomes were postoperative overall survival (OS) and disease‐free survival (DFS). We calculated the pooled hazard ratios (HR) with 95% confidence intervals (95% CI) of OS and DFS.

Results

Pooled analysis of six studies, with a total of 1697 patients with HCC beyond Milan criteria, did not reveal a statistically significant improvement in OS in patients undergoing LT vs LR (LT vs LR, HR: 0.83, 95% CI: 0.68‐1.01, P = .06), without significant heterogeneity (χ2 = 8.38, I2 = 40.3%, P = .137). Five studies with a total of 1511 patients were included in pooled analysis of DFS between LT and LR group. In the fixed‐effects model, patients in the LT group gained significantly better DFS (LT vs LR, HR: 0.45, 95% CI: 0.37‐0.56, P < .001) than patients in the LR group, with no significant heterogeneity (χ2 = 6.80, I2 = 41.6%, P = .144). Four studies provided the data of adjusted HRs (LT vs LR). In the fixed‐effects model, patients in the LT group had significantly better OS (HR: 0.58, 95% CI: 0.44‐0.77, P < .001, I2 = 0%) and DFS (HR: 0.14, 95% CI: 0.08‐0.23, P < .001, I2 = 0%) than those of patients in the LR group. The sensitivity analyses revealed that the results were robust.

Conclusion

Our meta‐analysis demonstrated that HBV‐related patients with HCC beyond Milan criterion who underwent LT gained better OS and DFS compared with patients who underwent LR after adjusting confounding factors.
Habitat modelling of tracking data from multiple marine predators identifies important areas in the Southern Indian Ocean
Authors: Reisinger Ryan R. , Raymond Ben , Hindell Mark A. , Bester Marthán N. , Crawford Robert J. M. , Davies Delia , de Bruyn P. J. Nico , Dilley Ben J. , Kirkman Stephen P. , Makhado Azwianewi B. , Ryan Peter G. , Schoombie Stefan , Stevens Kim , Sumner Michael D. , Tosh Cheryl A. , Wege Mia , Whitehead Thomas Otto , Wotherspoon Simon , Pistorius Pierre A.
Published: January 2018

Aim

The distribution of marine predators is driven by the distribution and abundance of their prey; areas preferred by multiple marine predator species should therefore indicate areas of ecological significance. The Southern Ocean supports large populations of seabirds and marine mammals and is undergoing rapid environmental change. The management and conservation of these predators and their environment relies on understanding their distribution and its link with the biophysical environment, as the latter determines the distribution and abundance of prey. We addressed this issue using tracking data from 14 species of marine predators to identify important habitat.

Location

Indian Ocean sector of the Southern Ocean.

Methods

We used tracking data from 538 tag deployments made over a decade at the Subantarctic Prince Edward Islands. For each real track, we simulated a set of pseudo‐tracks that allowed a presence‐availability habitat modelling approach that estimates an animal's habitat preference. Using model ensembles of boosted regression trees and random forests, we modelled these tracks as a response to a set of 17 environmental variables. We combined the resulting species‐specific models to evaluate areas of mean importance.

Results

Real tracking locations covered 39.75 million km2, up to 7,813 km from the Prince Edward Islands. Areas of high mean importance were located broadly from the Subtropical Zone to the Polar Frontal Zone in summer and from the Subantarctic to Antarctic Zones in winter. Areas of high mean importance were best predicted by factors including wind speed, sea surface temperature, depth and current speed.

Main conclusions

The models and predictions developed here identify important habitat of marine predators around the Prince Edward Islands and can support the large‐scale conservation and management of Subantarctic ecosystems and the marine predators they sustain. The results also form the basis of future efforts to predict the consequences of environmental change.
A cross‐sectional study of confidence in minor surgical skills amongst junior dentists
Authors: Keat R. M. , Sheik S. A. , Thomas M. , Albuquerque R. , Hill K.
Published: January 2018

Introduction

To work in the National Health Service (NHS) as a dentist, the practitioner needs to be on the UK dental “performer's list”. To apply for access to this list and work as a General Dental Practitioner (GDP), dentists must be qualified from the European Economic Area (EEA) or, those trained in the UK, must undertake Dental Foundation Training (DFT). Dentists interested in further taught learning or pursuing specialist training must continue working as “Dental Core Trainees” (DCTs). Most of these jobs are available in Oral and Maxillofacial Surgery (OMFS) Units and require dentists to undertake unsupervised surgical procedures.

It is currently estimated that over 400 “junior dentists” undertake DCT a year. It is the aim of this study to ascertain whether confidence in simple surgical procedures improves when compared to GDPs of similar experience.

Methods

One hundred and two junior dentists, 34 DFTs, 20 DCT1s, 21 DCT2s and 27 second and third year post‐DFT GDPs all working across the Midlands, UK, had Likert scale responses about confidence in 14 minor surgical skills assessed. Results were analysed to ascertain whether gender, year group and number of extractions had any effect on confidence.

Conclusions

We conclude that confidence in minor surgical procedures improves significantly when undertaking DCT OMFS posts, with the most significant improvement in confidence occurring within the first 6 months. Dental Core Trainees become significantly more confident in their surgical ability within the first 6 months when compared to GDPs with longer postgraduate experience.
Chimerism and gene therapy — Lessons learned from non‐conditioned murine bone marrow transplantation models
Authors: Jazbec Katerina , Jež Mojca , Smrekar Boštjan , Miceska Simona , Rožman Jasmina‐Živa , Švajger Urban , Završnik Janja , Malovrh Tadej , Rožman Primož
Published: January 2018

Objective

Hematopoietic stem and progenitor cells (HSPCs) can be used as a vector for gene therapies. In order to predict the number of HSPCs cells necessary to achieve the target level of chimerism in an autologous setting, syngeneic male bone marrow (BM) cells were transplanted into 35 non‐conditioned female BALB/c mice.

Method

The resulting chimerism was determined at 6‐53 weeks using qPCR, cell subpopulation sorting, and colony‐forming units (CFU) analysis.

Results

After the transplantation of 125.8 ± 2.5 million nucleated BM cells, the BM of recipients contained 20.0 ± 2.8% donor cells, representing a chimerism of 0.16 ± 0.02% per one million transplanted nucleated BM cells. Chimerism levels in the BM, neutrophils, and B cells were comparable, whereas in T cells it was lower, and in CFU was approximately twice greater than in BM.

Conclusion

By extrapolating our murine data, and data from some previous studies to a human non‐conditioned autologous CD34+ HSPC transplantation setting, we conclude that approximately 44 million CD34+ HSPCs would be needed to achieve 20% donor chimerism in a 70‐kg human, which could serve as a starting point for the future use of HSCPs in gene and cell therapy.