bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D, bones and muscle: myth versus reality
Authors: Duque Gustavo , Daly Robin M. , Sanders Kerrie , Kiel Douglas P. 
Published: March 2017

ObjectivesEvidence regarding the efficacy and dosing of vitamin D on fall and fracture prevention, with or without calcium, is characterised by uncertainty.MethodsA panel of experts was organised at the First Australasian Conference on Sarcopenia and Frailty in Melbourne, Australia, in November 2016 to provide an interpretation of the current evidence and to give their opinions regarding the supplementation of vitamin D in three hypothetical cases.Results and ConclusionThe authors conclude that (i) target serum 25(OH)D concentration should be 50 to 60 nmol/L year round, with a conservative upper limit <100 nmol/L; (ii) change in serum concentrations at any given dose is highly variable among individuals; (iii) dosing interval may need to be <2 months to have a continuous benefit; (iv) a loading dose can raise levels to target quickly, but there is no evidence yet that this has any positive effect on falls or fracture outcomes; and (v) a maintenance dose of 1000 IU/day, or given as an equivalent dose weekly or monthly, is sufficient for most individuals.
Successful use of Bruton's kinase inhibitor, ibrutinib, to control paraneoplastic pemphigus in a patient with paraneoplastic autoimmune multiorgan syndrome and chronic lymphocytic leukaemia
Authors: Lee Andrew , Sandhu Suneet , Imlay‐Gillespie Louise , Mulligan Stephen , Shumack Stephen 
Published: March 2017

AbstractWe present the case of a 51‐year‐old man who developed paraneoplastic pemphigus (PNP) in the context of chronic lymphocytic leukemia (CLL). His CLL was successfully controlled with ibrutinib. Concurrently, there was significant improvement of his PNP, suggesting that ibrutinib may be a very useful addition to the treatment options in this potentially life‐threatening autoimmune disorder.
Type I interferons modulate methotrexate resistance in gestational trophoblastic neoplasia
Authors: Elias Kevin M. , Harvey Richard A. , Hasselblatt Kathleen T. , Seckl Michael J. , Berkowitz Ross S. 
Published: March 2017

ProblemResistance to methotrexate is a leading clinical problem in gestational trophoblastic neoplasia (GTN), but there are limited laboratory models for this condition.Method of studyWe created isogenic trophoblastic cell lines resistant to methotrexate and compared these to the parent cell lines using gene expression microarrays and qRT‐PCR followed by mechanistic studies using recombinant cytokines, pathway inhibitors, and patient sera.ResultsGene expression microarrays and focused analysis by qRT‐PCR revealed methotrexate led to type I interferon upregulation, in particular interferon alpha 2 (IFNA2), and methotrexate resistance was associated with chronic low level increases in type I interferon expression. Recombinant IFNA2 imparted chemosensitive choriocarcinoma cells with partial resistance to methotrexate, while chemoresistant choriocarcinoma cells were uniquely sensitive to fludarabine, a STAT1 inhibitor. In pre‐treatment patient sera, IFNA2 levels correlated with subsequent resistance to methotrexate chemotherapy.ConclusionMethotrexate resistance is influenced by type I interferon signaling with prognostic and therapeutic implications for treating women with GTN.
Predictors of mode of birth and duration of labour following induction using prostaglandin vaginal gel
Authors: Beckmann Michael , Gibbons Kristen , Flenady Vicki , Kumar Sailesh 
Published: March 2017

Background and aimsUsing data from a randomised controlled trial (RCT) comparing two policies of prostaglandin (PGE2) vaginal gel induction of labour (IOL) at term, this study aimed to determine: (i) demographic/clinical factors that predict IOL outcomes; and (ii) clinical characteristic(s) of women who would benefit from a policy of amniotomy once technically possible as opposed to giving more PGE2.Material and methodsFollowing an initial PGE2 dose, women were randomised to amniotomy or repeat‐PGE2. Using RCT data, two multivariate models were developed, assessing the relationship between demographic/clinical characteristics and the outcomes of caesarean section (CS), and vaginal delivery within 24 h (VD < 24 h). Regression‐equations were used to predict the likelihood of CS and VD < 24 h, varying independent predictors from the multivariate analyses.ResultsOf 245 term women undergoing IOL, 90 had a CS, 155 delivered vaginally and 79 had a VD < 24 h. Controlling for confounders, nulliparity [adjusted odds ratio (aOR) = 3.71 (1.55, 8.88)] and modified Bishop's score (MBS) at first review [aOR = 0.78 (0.66, 0.92)] were independently associated with CS. Nulliparity [aOR = 0.06 (0.02, 0.15)], MBS at first review [aOR = 1.66 (1.35, 2.05)], and a policy of early amniotomy [aOR = 2.28 (1.04, 5.00)] were associated with VD < 24 h. Modelling using regression equations, and varying both MBS at first review and parity, there was no scenario where repeat PGE2 was predicted to be superior to an earlier amniotomy.ConclusionsFollowing IOL using PGE2 vaginal gel at term, both parity and cervical favourability at first review are associated with CS and VD < 24 h. All combinations of parity and MBS at first review predicted fewer CS and greater likelihood of VD < 24 h with a policy of amniotomy once technically possible.
Guidelines in lower‐middle income countries
Authors: Olayemi Edeghonghon , Asare Eugenia V. , Benneh‐Akwasi Kuma Amma A. 
Published: March 2017

SummaryGuidelines include recommendations intended to optimize patient care; used appropriately, they make healthcare consistent and efficient. In most lower‐middle income countries (LMICs), there is a paucity of well‐designed guidelines; as a result, healthcare workers depend on guidelines developed in Higher Income Countries (HICs). However, local guidelines are more likely to be implemented because they are applicable to the specific environment; and consider factors such as availability of resources, specialized skills and local culture. If guidelines developed in HICs are to be implemented in LMICs, developers need to incorporate local experts in their development. Involvement of local stakeholders may improve the rates of implementation by identifying and removing barriers to implementation in LMICs. Another option is to encourage local experts to adapt them for use in LMICs; these guidelines may recommend strategies different from those used in HICs, but will be aimed at achieving the best practicable standard of care. Infrastructural deficits in LMICs could be improved by learning from and building on the successful response to the human immunodeficiency virus/acquired immunodeficiency syndrome pandemic through interactions between HICs and LMICs. Similarly, collaborations between postgraduate medical colleges in both HICs and LMICs may help specialist doctors training in LMICs develop skills required for guideline development and implementation.
The practice and perception of precautionary allergen labelling by the Australasian food manufacturing industry
Authors: Zurzolo G. A. , Peters R. L. , Koplin J. J. , de Courten M. , Mathai M. L. , Tye‐Din J. A. , Tang M. L. K. , Campbell D. E. , Ponsonby A‐L. , Prescott S. L. , Gurrin L. , Dharmage S.C. , Allen K. J. 
Published: March 2017

SummaryBackgroundThe precautionary allergen labelling (PAL) and Voluntary Incidental Trace Allergen Labelling (VITAL®) tools were designed by industry to assist consumers with selecting safe foods for consumption. However, a sizeable proportion of food products bear no label, and it is unclear whether these products are free from allergens and therefore safe to consume or have simply not undergone a risk assessment and therefore remain unlabelled for that reason.ObjectiveTo assess the prevalence of unlabelled products that have undergone a risk assessment process and to examine the factors influencing industry's uptake of the VITAL® process.MethodsA web‐based questionnaire was distributed to Australasian food and grocery manufacturers.ResultsOne hundred and thirty‐seven Australasian manufacturers were contacted, and 59 questionnaires were returned (response rate: 43%). The respondents represented 454 different manufacturing sites. Manufacturers reported that 23% (95% CI 19‐28) of products (n=102/434) that had been through the VITAL® risk assessment process had no PAL statement on the label. 34% (95% CI 30‐38), (n=204/600) of products that had undergone another (non‐VITAL®) risk assessment process had no PAL statement. In examining the factors that influenced industry's uptake of the VITAL® process, 25 manufacturers reported on factors that influenced the uptake of the VITAL® process, 76% (CI 95% 55‐91) reported that VITAL® was an effective tool because it was based on science; 52% (CI 95% 31‐72) reported that it was too time‐consuming and 36% (CI 95% 18‐57) identified a concern with it not being endorsed by the government.Conclusion and Clinical RelevanceCurrently, we estimate that at least 30% of products may have been through a risk assessment process and yet bear no PAL statement on the label. Permissive labelling could be incorporated onto these products if they have been assessed to be safe for consumption.
Nadroparin carries a potentially high risk of inducing cutaneous delayed‐type hypersensitivity responses
Authors: Schindewolf Marc , Recke Andreas , Zillikens Detlef , Lindhoff‐Last Edelgard , Ludwig Ralf J. 
Published: March 2017

SummaryBackgroundHeparins are widely used for the prophylaxis/treatment of thromboembolic events. As adverse effects, heparin‐induced skin lesions occur frequently (in 7.5–39% of patients). Skin lesions may be the only clinical manifestation of life‐threatening immune‐mediated heparin‐induced thrombocytopenia, but are commonly caused by a delayed‐type hypersensitivity response [heparin‐induced delayed‐type hypersensitivity (HIHS)]. Risk factors have not been prospectively identified.ObjectivesTo identify possible risk factors for heparin‐induced skin lesions from three independent clinical trials in a combined analysis.MethodsA pooled analysis from prospective studies was performed, and possible risk factors were included in a multiple logistic regression analysis.ResultsObesity (body mass index of > 25), prolonged anticoagulant therapy, prior heparin exposure and younger age (< 55 years) were confirmed as independent risk factors for HIHS. The choice of anticoagulant preparation had the greatest influence. On comparison of dalteparin, enoxaparin, fondaparinux, unfractionated heparin, and nadroparin, the latter was associated with the highest risk of eliciting HIHS (odds ratio of 30.2, 95%CI: 11.7–77.9).ConclusionsThe high risk associated with nadroparin has been validated in controlled trials, and this emphasizes the singularity of each heparin preparation in terms of allergenicity and that individualized anticoagulation is required.
Further Tests of a Dynamic‐Adjustment Account of Saccade Targeting During the Reading of Chinese
Authors: Liu Yanping , Huang Ren , Gao Dingguo , Reichle Erik D. 
Published: March 2017

AbstractThere are two accounts of how readers of unspaced writing systems (e.g., Chinese) know where to move their eyes: (a) saccades are directed toward default targets (e.g., centers of words that have been segmented in the parafovea); or (b) saccade lengths are adjusted dynamically, as a function of ongoing parafoveal processing. This article reports an eye‐movement experiment supporting the latter hypothesis by demonstrating that the slope of the relationship between the saccade launch site on word N and the subsequent fixation landing site on word N + 1 is > 1, suggesting that saccades are lengthened from launch sites that afford more parafoveal processing. This conclusion is then evaluated and confirmed via simulations using implementations of both hypotheses (Liu, Reichle, & Li, 2016), with a discussion of these results for our understanding of saccadic targeting during reading and existing models of eye‐movement control.
Alcohol consumption by breastfeeding mothers: Frequency, correlates and infant outcomes
Authors: Wilson Judy , Tay Rui Yang , McCormack Clare , Allsop Steve , Najman Jake , Burns Lucy , Olsson Craig A. , Elliott Elizabeth , Jacobs Sue , Mattick Richard P. , Hutchinson Delyse 
Published: March 2017

AbstractIntroduction and AimsThere is limited research regarding the effects of alcohol consumption by breastfeeding mothers on infant development. This study examined the frequency, correlates and outcomes of alcohol use during lactation.Design and MethodsData were from an Australian cohort study. Maternal demographics and substance use were assessed during pregnancy and at 8 weeks and 12 months postpartum. Breastfeeding duration, infant feeding, sleeping and development (Ages and Stages Questionnaire) were also assessed postpartum. Logistic regression and general linear model analyses examined characteristics of women who drank during breastfeeding, and the association between alcohol use during breastfeeding and infant outcomes.ResultsAlcohol use was reported by 60.7% and 69.6% of breastfeeding women at 8 weeks and 12 months postpartum, respectively. Breastfeeding women who consumed alcohol were more likely to be born in Australia or another English‐speaking country, be tertiary educated and have higher household incomes. Most drank at low levels (≤14 standard drinks per week, <3 per occasion) and employed strategies (e.g. timing of alcohol use) to minimise alcohol passed onto infants via breastmilk. Alcohol consumption was unrelated to breastfeeding duration, infant feeding and sleeping behaviour at 8 weeks, and most infant developmental outcomes at 8 weeks or 12 months, after adjusting for confounders. The only significant association showed that infants whose mothers drank at 8 weeks postpartum had more favourable results for personal‐social development at 12 months compared with those whose mothers abstained.Discussion and ConclusionsLow level drinking during breastfeeding is not linked with shorter breastfeeding duration or adverse outcomes in infants up to 12 months of age. [Wilson J, Tay RY, McCormack C, Allsop S, Najman J, Burns L, Olsson CA, Elliott E, Jacobs S, Mattick RP, Hutchinson D. Alcohol consumption by breastfeeding mothers: Frequency, correlates and infant outcomes. Drug Alcohol Rev 2017;00:000‐000]
Health service utilisation attributable to methamphetamine use in Australia: Patterns, predictors and national impact
Authors: McKetin Rebecca , Degenhardt Louisa , Shanahan Marian , Baker Amanda L. , Lee Nicole K. , Lubman Dan I. 
Published: March 2017

AbstractAim and background. We estimated health service utilisation attributable to methamphetamine use, its national impact and examined other predictors of health service utilisation among dependent methamphetamine users. Method. Past year rates of health service utilisation (number of attendances for general hospitals, psychiatric hospitals, emergency departments, general practitioners, psychiatrists, counsellors or psychologists, and dentists) were estimated for three levels of methamphetamine use (no use, < weekly, ≥ weekly) using panel data from a longitudinal cohort of 484 dependent methamphetamine users from Sydney and Brisbane, Australia. Marginal rates for methamphetamine use were multiplied by 2013 prevalence estimates from the National Drug Strategy Household Survey. Covariates included other substance use, demographics, mental disorders and drug treatment. Findings. Health service use was high. More frequent methamphetamine use was associated with more frequent presentations to emergency departments (incidence rate ratios 1.3–2.1) and psychiatric hospitals (incidence rate ratios 5.3–8.3) and fewer presentations to general practitioners, dentists and counsellors. We estimate methamphetamine use accounted for between 28 400 and 80 900 additional psychiatric hospital admissions and 29 700 and 151 800 additional emergency department presentations in 2013. More frequent presentations to these services were also associated with alcohol and opioid use, comorbid mental health disorders, unemployment, unstable housing, attending drug treatment, low income and lower education. Conclusions. Frequent methamphetamine use has a significant impact on emergency medical and psychiatric services. Better provision of non‐acute health care services to address the multiple health and social needs of dependent methamphetamine users may reduce the burden on these acute care services. [McKetin R, Degenhardt L, Shanahan M, Baker AL, Lee NK, Lubman DI. Health service utilisation attributable to methamphetamine use in Australia: patterns, predictors and national impact. Drug Alcohol Rev 2017;00:000–000]
Mapping language to the world: the role of iconicity in the sign language input
Authors: Perniss Pamela , Lu Jenny C. , Morgan Gary , Vigliocco Gabriella 
Published: March 2017

AbstractMost research on the mechanisms underlying referential mapping has assumed that learning occurs in ostensive contexts, where label and referent co‐occur, and that form and meaning are linked by arbitrary convention alone. In the present study, we focus on iconicity in language, that is, resemblance relationships between form and meaning, and on non‐ostensive contexts, where label and referent do not co‐occur. We approach the question of language learning from the perspective of the language input. Specifically, we look at child‐directed language (CDL) in British Sign Language (BSL), a language rich in iconicity due to the affordances of the visual modality. We ask whether child‐directed signing exploits iconicity in the language by highlighting the similarity mapping between form and referent. We find that CDL modifications occur more often with iconic signs than with non‐iconic signs. Crucially, for iconic signs, modifications are more frequent in non‐ostensive contexts than in ostensive contexts. Furthermore, we find that pointing dominates in ostensive contexts, and suggest that caregivers adjust the semiotic resources recruited in CDL to context. These findings offer first evidence for a role of iconicity in the language input and suggest that iconicity may be involved in referential mapping and language learning, particularly in non‐ostensive contexts.
Placebo‐controlled, randomized trial of the addition of once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (AWARD‐9)
Authors: Pozzilli Paolo , Norwood Paul , Jódar Esteban , Davies Melanie J. , Ivanyi Tibor , Jiang Honghua , Woodward D. Bradley , Milicevic Zvonko 
Published: March 2017

AimTo compare the addition of weekly dulaglutide vs the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub‐optimum glycated haemoglobin (HbA1c) concentration.Materials and MethodsPatients (N = 300) from this phase III, double‐blind, parallel‐arm, placebo‐controlled study were randomized to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± standard deviation baseline dose: 39 ± 22 U), with or without metformin (≥1500 mg/d). The primary endpoint was superiority of dulaglutide/glargine to placebo/glargine with regard to change from baseline in HbA1c level at 28 weeks.ResultsLeast squares (LS) mean ± standard error (s.e.) HbA1c changes from baseline were −1.44 ± 0.09% (−15.74 ± 0.98 mmol/mol) with dulaglutide/glargine and −0.67 ± 0.09% (−7.32 ± 0.98 mmol/mol) with placebo/glargine at 28 weeks (LS mean difference [95% confidence interval] −0.77% [−0.97, −0.56]; P < .001). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: −2.41 ± 0.39 kg; P < .001). Increases from baseline in mean glargine dose were significantly smaller with dulaglutide/glargine vs placebo/glargine (13 ± 2 U [0.1 ± 0.02 U/kg] vs 26 ± 2 U [0.3 ± 0.02 U/kg], respectively; P < .001; LS mean ± s.e. final dose: dulaglutide/glargine, 51 ± 2 U; placebo/glargine, 65 ± 2 U). The hypoglycaemia rate (≤3.9 mmol/L threshold) was 7.69 ± 15.15 and 8.56 ± 16.13 events/patient/year, respectively (P = .488). One episode of severe hypoglycaemia occurred in the dulaglutide/glargine group. Common gastrointestinal adverse events with dulaglutide were nausea (12.0%), diarrhoea (11.3%) and vomiting (6.0%).ConclusionsWeekly dulaglutide 1.5 mg added to basal insulin is an efficacious and well tolerated treatment option for patients with T2D.
Insulin degludec: Lower day‐to‐day and within‐day variability in pharmacodynamic response compared with insulin glargine 300 U/mL in type 1 diabetes
Authors: Heise Tim , Nørskov Marianne , Nosek Leszek , Kaplan Kadriye , Famulla Susanne , Haahr Hanne L. 
Published: March 2017

AimTo compare day‐to‐day and within‐day variability in glucose‐lowering effect between insulin degludec (IDeg) and insulin glargine 300 U/mL (IGlar‐U300) in type 1 diabetes.Materials and methodsIn this double‐blind, crossover study, patients were randomly assigned to 0.4 U/kg of IDeg or IGlar‐U300 once daily for two treatment periods lasting 12 days each. Pharmacodynamic variables were assessed at steady‐state from the glucose infusion rate profiles of three 24‐hour euglycaemic glucose clamps (days 6, 9 and 12) during each treatment period.ResultsOverall, 57 patients completed both treatment periods (342 clamps). The potency of IGlar‐U300 was 30% lower than IDeg (estimated ratio 0.70, 95% confidence interval [CI] 0.61; 0.80;
P
< .0001). The distribution of glucose‐lowering effect was stable across 6‐hour intervals (24%‐26%) for IDeg, while IGlar‐U300 had greater effects in the first (35%) and last (28%) intervals compared with 6 to 12 hours (20%) and 12 to 18 hours (17%). Within‐day variability (relative fluctuation) was 37% lower with IDeg than with IGlar‐U300 (estimated ratio IDeg/IGlar‐U300: 0.63, 95% CI 0.54; 0.73;
P
< .0001). The day‐to‐day variability in glucose‐lowering effect with IDeg was approximately 4 times lower than IGlar‐U300 (variance ratio IGlar‐U300/IDeg: 3.70, 95% CI 2.42; 5.67;
P
< .0001). The day‐to‐day variability in glucose‐lowering effect assessed in 2‐hour intervals was consistently low with IDeg over 24 hours, but steadily increased with IGlar‐U300 to a maximum at 10 to 12 hours and 12 to 14 hours after dosing (variance ratios 12.4 and 11.4, respectively).Conclusion
IDeg has lower day‐to‐day and within‐day variability than IGlar‐U300 and a more stable glucose‐lowering effect, which might facilitate titration and enable tighter glycaemic control with a reduced risk of hypoglycaemia.