bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1, randomized, placebo‐controlled, dose‐escalation study of an anti‐IL‐13 monoclonal antibody in healthy subjects and mild asthmatics
Authors: Hodsman Peter , Ashman Claire , Cahn Anthony , De Boever Erika , Locantore Nicholas , Serone Adrian , Pouliquen Isabelle 
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• IL‐13 can recapitulate the key pathological and clinical features of asthma.• Exhaled NO (FeNO) concentrations are elevated under conditions of pulmonary inflammation, including asthma.• Therapies that inhibit signalling by both IL‐13 and the functionally redundant cytokine IL‐4 have demonstrated reductions in FeNO, although relationship to dose was not reported.WHAT THIS STUDY ADDS• This study provides the first report of the safety and pharmacokinetics of GSK679586, a novel humanized monoclonal antibody that prevents IL‐13 from binding its two known receptors.• This is the first report of the effects on FeNO of a therapy targeting IL‐13 alone. Inhibition of IL‐13 signalling by GSK679586 produces dose‐ and time‐dependent reductions in FeNO in mild intermittent asthmatics. Thus, FeNO appears to be a dose‐ and time‐responsive clinical biomarker of IL‐13 inhibition in mild asthma.AIMS IL‐13 is implicated as an important mediator of the pathology of asthma. This first clinical study with GSK679586, a novel humanized anti‐IL‐13 IgG1 monoclonal antibody, evaluated the safety, pharmacokinetics and pharmacodynamics of escalating single and repeat doses of GSK679586.METHODS In this randomized, double‐blind study, healthy subjects received single intravenous infusions of GSK679586 (0.005, 0.05, 0.5, 2.5, 10 mg kg−1) or placebo and mild intermittent asthmatics received two once monthly intravenous infusions of GSK679586 (2.5, 10, 20 mg kg−1) or placebo.RESULTS GSK679586 displayed approximately linear pharmacokinetics (based on AUC and Cmax) with limited accumulation upon repeat administration. In mild intermittent asthmatics, treatment with GSK679586 produced an increase in serum total IL‐13 concentrations, indicative of GSK679586–IL‐13 complex formation. Additionally, mean levels of exhaled nitric oxide (FeNO), a marker of pulmonary inflammation, were reduced relative to baseline at 2.5, 10 and 20 mg kg−1 doses of GSK679586 at both 2 weeks (19%, 44% and 52% decreases) and 8 weeks (29%, 55% and 42% decreases) after the second infusion. GSK679586 was well tolerated; the incidence of AEs was comparable across all presumed biologically active doses and there were no treatment‐related SAEs.CONCLUSIONS GSK679586 demonstrated dose‐dependent pharmacological activity in the lungs of mild intermittent asthmatics. These findings, together with the favourable safety profile and advantageous PK characteristics of a monoclonal antibody (e.g. a long half‐life supporting less frequent dosing), warrant further investigation of GSK679586 in a broader asthma patient population.
The pharmacokinetics and pharmacodynamics of single dose (R)‐ and (S)‐warfarin administered separately and together: relationship to VKORC1 genotype
Authors: Maddison John , Somogyi Andrew A. , Jensen Berit P. , James Heather M. , Gentgall Melanie , Rolan Paul E. 
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The contribution of (S)‐warfarin to the clinical effect of rac‐warfarin is well understood. The extent to which (R)‐warfarin contributes to the clinical effect of rac‐warfarin is unclear.WHAT THIS STUDY ADDS• Using unequivocally pure (R)‐ and (S)‐warfarin we have demonstrated that (R)‐warfarin contributes to the hypoprothrombinaemic effect of single large doses of warfarin.• The extent of the interaction is dependent on VKORC1 genotype.AIMS 1) To determine the pharmacokinetics and pharmacodynamics of (R)‐ and (S)‐warfarin given alone and in combination and 2) to determine whether the relative potency of (R)‐ and (S)‐warfarin is dependent on VKORC1 genotype.METHODS A three way crossover study was conducted in which 17 healthy male subjects stratified by VKORC1 1173 C>T genotype and all CYP2C9 1*/1* received (R)‐warfarin 80 mg, (S)‐warfarin 12.5 mg and rac‐warfarin sodium 25 mg. Plasma (R)‐ and (S)‐warfarin unbound and total concentrations and prothrombin time were determined at multiple time points to 168 h.RESULTS Pharmacokinetic parameters for (R)‐ and (S)‐warfarin were similar to the literature. (R)‐warfarin 80 mg alone resulted in a mean AUCPT (0,168 h) of 3550 s h (95% CI 3220, 3880). Rac‐warfarin sodium 25 mg containing (S)‐warfarin 11.7 mg produced a greater effect on AUCPT (0,168 h) than (S)‐warfarin 12.5 mg (mean difference 250 s.h, 95% CI 110, 380, P < 0.002) given alone. In a mixed effects model the ratio of response between (R)‐ and (S)‐warfarin (AUCPT((R)‐warfarin) : AUCPT((S)‐warfarin)) was 1.21 fold higher (95% CI 1.05, 1.41, P < 0.02) in subjects of VKORC1 TT genotype compared with the CC genotype.CONCLUSIONS (R)‐warfarin has a clear PD effect and contributes to the hypoprothrombinaemic effect of rac‐warfarin. VKORC1 genotype is a covariate of the relative R/S potency relationship. Prediction of drug interactions with warfarin needs to consider effects on (R)‐warfarin PK and VKORC1 genotype.
Prospective parallel randomized trial of the MultiCyte™ ThinPrep® imaging system: the Scottish experience
Authors: Palmer T. J. , Nicoll S. M. , McKean M. E. , Park A. J. , Bishop D. , Baker L. , Imrie J. E. A. 
Published: May 2012

T.J. Palmer, S.M. Nicoll, M.E. McKean, A.J. Park, D. Bishop, L. Baker and J.E.A. Imrie  Prospective parallel randomized trial of the MultiCyte™ ThinPrep® imaging system: the Scottish experienceBackground:  Computer‐assisted screening of cervical liquid‐based cytology (LBC) preparations using the ThinPrep® Imaging System (TIS) has shown improved qualitative and quantitative gains. The use of Multicyte™ has not been described in a well‐established national screening programme with a low incidence of high‐grade dyskaryosis.Objectives:  To assess the impact of computer‐assisted screening within the Scottish Cervical Screening Programme (SCSP).Methods:  Two groups of three laboratories, each sharing a ThinPrep® Imager, screened 79 366 slides randomized to test and 90 551 to control arms by laboratory accession. Screeners were not blinded. Standard laboratory reporting profiles of the SCSP, sensitivity, specificity and false‐negative rates of all grades of LBC abnormalities with respect to final cytology reports, predictive value for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on histology; and screening rates were compared for both arms.Results:  Inadequate and negative reporting rates were significantly lower and low‐grade reporting rates significantly higher in the imager arm. Imager‐assisted screening showed significantly better specificity than manual screening with respect to the final cytology result. There was no evidence of a significant difference in the detection of CIN2 +  or CIN3 + . Positive, abnormal and total predictive values (high‐grade, low‐grade and all abnormal cytology found to be CIN2 + , respectively) were similar in both arms. Productivity was significantly higher in the imager arm.Conclusion:  Computer‐assisted screening in a well established screening programme showed significantly improved productivity without loss of quality. These findings should inform future policy for cervical screening programmes.
Proton pump inhibitors prescribing following the introduction of generic drugs
Authors: Cammarota Simona , Bruzzese Dario , Sarnelli Giovanni , Citarella Anna , Menditto Enrica , Riegler Salvatore , Savino Ivana G. , Vozzella Letizia , Piccinocchi Gaetano , Napoli Luigi , Arpino Giovanni , Cuomo Rosario 
Published: May 2012

Eur J Clin Invest 2012; 42 (10): 1068–1078AbstractBackground  In many countries, the introduction of generic proton pump inhibitors (PPIs) onto the pharmaceutical market increased the phenomenon of therapeutic substitution in acid‐related disorders (ARDs).Aim  To investigate the treatment of ARDs in an Italian primary care setting from 2005 to 2008 by verifying: (i) dynamics of PPI prescribing; (ii) predictors of PPI switching; and (iii) healthcare resource consumption costs.Methods  This was a retrospective cohort study of 102 general practitioners (GPs) who managed an average of 150 000 inhabitants in Naples. Multilevel logistic regression was used to assess the potential predictors of both PPI switching and termination. Primary care costs were expressed as the cost of ARD management per PPI user year.Results  The percentage of PPI users with ARD increased from 5·5% (2005) to 7·0% (2008) (P < 0·0001), especially for dyspepsia (from 9·5% to 13·7%; P < 0·0001) and chronic treatments (from 23·4% to 29·4%; P < 0·0001). PPI switching rose from 13·0% to 16·7% during the period observed (P < 0·0001). Calendar years, long‐term treatments and gastroesophageal reflux disease were positive predictors of PPI switching. Primary care costs relating to PPI switchers increased by 61·14€ compared with nonswitchers (P < 0·0001).Conclusions  The introduction of generic PPIs onto the Italian market was associated with an increasing amount of PPI prescribing related to chronic treatments, unlicensed indications (e.g. dyspespsia) and therapeutic substitutions. Growing overall costs linked to the phenomenon of PPI switching was also found. Our data support the need to assess the effects of the introduction of generic drugs on both clinical outcomes and the cost management of ARDs.
Living a demanding life – spouses’ experiences of living with a person suffering from intermittent claudication
Authors: Egberg Louise , Andreassen Sissel , Mattiasson Anne‐Cathrine 
Published: May 2012

egberg l., andreassen s. & mattiasson a‐c. (2013) Living a demanding life – spouses’ experiences of living with a person suffering from intermittent claudication. Journal of Advanced Nursing69(3), 610–618. doi: 10.1111/j.1365‐2648.2012.06043.xAbstractAim.  To report a study of family members’ experiences of living with a person suffering from intermittent claudication caused by peripheral arterial disease.Background.  Intermittent claudication is a symptom caused by peripheral arterial disease. Walking ability is reduced due to pain and this also affects the family members and leads to consequences such as isolation and a restricted life.Design.  This study has a qualitative descriptive design.Methods.  Ten spouses living with a person suffering from intermittent claudication were interviewed between December 2009–June 2010. The interviews were then analysed using qualitative thematic analysis.Findings.  Four themes were identified: ‘Frustrating to not meet intentions’, ‘Undergoing changes in social life’, ‘Being a person on the side of things’ and ‘Intertwining of circumstances’. The overall theme ‘Living a demanding life’ illustrates that intermittent claudication has great impact on daily life among spouses.Conclusion.  This study gives an insight into the complexities and the difficulties of living together with someone suffering from intermittent claudication, a symptom that has great impact on both the spouses’ and the ill persons’ lives. According to the findings in this study, it is important to gain knowledge about the spouses’ experiences because an holistic perspective is essential to treat and support the ill persons and their spouses.
Using biological traits to explain ladybird distribution patterns
Authors: Comont Richard F. , Roy Helen E. , Lewis Owen T. , Harrington Richard , Shortall Christopher R. , Purse Bethan V. 
Published: May 2012

AbstractAim Determining to what extent differing distribution patterns are governed by species’ life‐history and resource‐use traits may lead to an improved understanding of the impacts of environmental change on biodiversity. We investigated the extent to which traits can explain distribution patterns in the ladybird fauna (Coleoptera: Coccinellidae) of Great Britain.Location The British mainland and inshore islands (Anglesey, the Isle of Wight and the Inner Hebrides).Methods The distributions of 26 ladybird species resident in Britain were characterized in terms of their range size (from 2661 10‐km grid squares across Britain) and proportional range fill (at 10‐ and 50‐km scales). These were assessed relative to five traits (body length, elytral colour pattern polymorphism, voltinism, habitat specificity and diet breadth). The role of phylogenetic autocorrelation was examined by comparing the results of phylogenetic and generalized least‐squares regressions.Results Diet breadth was the only trait correlated with range size: species with broad diets had larger range sizes than dietary specialists. Range fill was sensitive to recording intensity (a per‐species measure of the mean number of records across occupied squares); models including both recording intensity and range size provided more explanatory power than models incorporating ecological traits alone.Main conclusions Habitat specificity is often invoked to explain the distribution patterns of species, but here we found diet breadth to be the only ecological correlate of both range fill and range size. This highlights the importance of understanding predator–prey interactions when attempting to explain the distribution patterns of predatory species. Our results suggest that the diet breadth of predatory species is a better correlate of range size and fill than other measures, such as habitat specificity.
Fragmented esophageal smooth muscle contraction segments on high resolution manometry: a marker of esophageal hypomotility
Authors: Porter R. F. , Kumar N. , Drapekin J. E. , Gyawali C. P. 
Published: May 2012

AbstractBackground  Esophageal peristalsis consists of a chain of contracting striated and smooth muscle segments on high resolution manometry (HRM). We compared smooth muscle contraction segments in symptomatic subjects with reflux disease to healthy controls.Methods  High resolution manometry Clouse plots were analyzed in 110 subjects with reflux disease (50 ± 1.4 years, 51.5% women) and 15 controls (27 ± 2.1 years, 60.0% women). Using the 30 mmHg isobaric contour tool, sequences were designated fragmented if either smooth muscle contraction segment was absent or if the two smooth muscle segments were separated by a pressure trough, and failed if both smooth muscle contraction segments were absent. The discriminative value of contraction segment analysis was assessed.Key Results  A total of 1115 swallows were analyzed (reflux group: 965, controls: 150). Reflux subjects had lower peak and averaged contraction amplitudes compared with controls (P < 0.0001 for all comparisons). Fragmented sequences followed 18.4% wet swallows in the reflux group, compared with 7.5% in controls (P < 0.0001), and were seen more frequently than failed sequences (7.9% and 2.5%, respectively). Using a threshold of 30% in individual subjects, a composite of failed and/or fragmented sequences was effective in segregating reflux subjects from control subjects (P = 0.04).Conclusions & Inferences  Evaluation of smooth muscle contraction segments adds value to HRM analysis. Specifically, fragmented smooth muscle contraction segments may be a marker of esophageal hypomotility.
High frequency of overlap between functional dyspepsia and overactive bladder
Authors: Matsuzaki J. , Suzuki H. , Fukushima Y. , Hirata K. , Fukuhara S. , Okada S. , Hibi T. 
Published: May 2012

AbstractBackground  Overactive bladder syndrome (OAB) is defined as a symptom complex comprising urgency, with or without urge incontinence, and usually frequency and nocturia. The association between irritable bowel syndrome (IBS) and bladder symptoms has been reported. This study is designed to investigate whether functional dyspepsia (FD), like IBS, is associated with OAB.Methods  A web surveys containing questions about OAB, FD, IBS, and demographics were completed by 5494 public individuals (2302 men and 3192 women) who have no history of severe illness. The prevalence and overlap of OAB, FD, and IBS were examined.Key Results  Among participants with FD, 20.5% could also be diagnosed with OAB (odds ratio [OR]: 2.85; 95% confidence interval [CI]: 2.21–3.67). Although concomitant FD and IBS were more strongly associated with OAB (OR: 4.34; 95% CI: 2.81–6.73), OAB was also highly prevalent among participants with FD but without IBS (OR: 3.09; 95% CI: 2.29–4.18). Among participants with FD, an overlapping OAB condition was more prevalent in those with both postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) (OR: 3.75; 95% CI: 2.48–5.67) than in those with PDS or EPS alone. Among participants with OAB, the severity of bladder symptoms was greater in participants with dyspeptic symptoms than without them.Conclusions & Inferences  Overactive bladder syndrome is common among FD patients, even if they do not have IBS. To improve FD patients’ quality of life, it will be important to provide management for OAB.
Bilateral lung transplant for hereditary hemorrhagic telangiectasia in a pediatric patient
Authors: Misra Meghna V. , Mullen Mary P. , Vargas Sara O. , Kim Heung Bae , Boyer Debra 
Published: May 2012

Misra MV, Mullen MP, Vargas SO, Kim HB, Boyer D. Bilateral lung transplant for hereditary hemorrhagic telangiectasia in a pediatric patient.Abstract:  HHT is an autosomal dominant vascular dysplasia, in which abnormalities of endothelial cells cause patients to develop mucocutaneous telangiectasias, and AVMs of the pulmonary, hepatic, and cerebral circulations. Pulmonary AVMs occur in more than 20% of patients with HHT, and presentation varies from simple diffuse telangiectasias to large complex structures. Surgical management is usually indicated for large pulmonary AVMs. Treatment options for pulmonary AVMs include therapeutic embolization, segmental or lobar resection of the affected lung, and less commonly lung transplantation. Here we report the first successful case of a bilateral lung transplant for a four‐yr‐old girl with HHT.
Late graft failure in FA – case report and review of the literature
Authors: Ehlert Karoline , Groll Andreas H. , Rossig Claudia , Fruehwald Michael C. , Juergens Heribert 
Published: May 2012

Ehlert K, Groll AH, Rossig C, Fruehwald MC, Juergens H. Late graft failure in FA – case report and review of the literature.Abstract:  Hematological disorders in patients with FA can only be cured by allogeneic HSCT. Severe infections in primary and early secondary graft failures pose a particular risk. Whereas most graft failures occur within 100 days, those observed after day +100 are infrequent. Here, we present our analysis of a secondary graft failure more than five yr after a first allogeneic HSCT. In this patient, isolated thrombocytopenia over a period of 12 months resulted in a chimerism subset analysis revealing a considerable decrease in the CD34‐positive donor cell fraction. After a second fludarabine‐based preparative regimen, the patient received PBSC from the same donor. Chimerism returned to full donor in all subsets. This clinical course demonstrates that isolated thrombocytopenia can precede complete graft failure for several months. Our review of the literature on late graft failures in patients with FA after day +100 reveals the absence of fludarabine in the preparative regimen as a potential risk factor. Further clinical research is necessary to identify more suitable approaches for ensuring safe and stable engraftment.
Effect of current breastfeeding on sleep patterns in infants from Asia‐Pacific region
Authors: Ramamurthy Mahesh Babu , Sekartini Rini , Ruangdaraganon Nichara , Huynh Duy Houng T , Sadeh Avi , Mindell Jodi A 
Published: May 2012

Aim:  The aim of this study was to assess the relationship between breastfeeding and sleep patterns in infants from Asia‐Pacific region.Methods:  Parents of 10 321 infants (0–11 months) from Australia, China, Hong Kong, India, Indonesia, Korea, Japan, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand and Vietnam completed an expanded version of the Brief Infant Sleep Questionnaire.Results:  Overall, 4714 (45.72%) were currently being breastfed; 61.3% of those between 0 and 5 months and 36.6% of those between 6 and 11 months. Currently breastfed infants, when compared with not currently breastfed infants, had a significant increase in the number and duration of night‐time wakings and less consolidated sleep. Interestingly, currently breastfed infants less than 6 months also showed longer duration of daytime sleep and obtained more sleep overall. Of note, of those who were currently breastfed, those infants who were nursed back to sleep during night, woke up more often at night (2.41 vs. 1.67 times) and had shorter continuous night‐time sleep period (5.58 vs. 6.88 h; P < 0.001). There was no significant difference between breastfeeding and non‐breastfeeding infants in the number of night wakings, when the nursing to sleep variable was controlled for in the analysis of variance.Conclusion:  Breastfeeding is associated with reduced sleep consolidation in infants. This relationship, however, may be moderated by parenting practices of nursing to sleep and back to sleep during the night. Thus, parents of infants with night waking problems should be encouraged to limit the association between nursing and falling to sleep, to improve sleep while maintaining breastfeeding.
Sleep problems and mental health in primary school new entrants: Cross‐sectional community‐based study
Authors: Quach Jon , Hiscock Harriet , Wake Melissa 
Published: May 2012

Aims:  To determine at school entry (i) the prevalence and types of child sleep problems; (ii) sleep difficulties and hygiene practices associated with sleep problems; and (iii) their associations with child health‐related quality of life, mental health and parent mental health.Methods:  We conducted a cross‐sectional community‐based study at 22 primary schools in Melbourne, Australia. One thousand five hundred and twelve (70%) parents of children in the first 6 months of the child's first year of primary school took part. Parent report of child sleep problems (none, mild, and moderate/severe); sleep difficulties; pre‐bedtime activities (television in bedroom, television or electronic games before bedtime, television or electronic games >2 h/day) and caffeine intake; child mental health (Strengths and Difficulties Questionnaire), health‐related quality of life (Pediatric Quality of Life Inventory); and parent mental health (Depression Anxiety Stress Scale‐21).Results:  38.6% of children had a parent‐reported sleep problem (27.9% mild, 10.8% moderate/severe). Sleep problems were characterised by problematic sleep difficulties but not poor sleep hygiene practices. Moderate/severe sleep problems were associated with poorer child mental health (mean difference −0.8; 95% confidence interval (CI) −1.1 to −0.5, P < 0.001), health‐related quality of life (mean difference −9.9; 95% CI −11.9 to −7.9, P < 0.001) and parent mental health (mean difference 9.8; 95% CI 7.7–11.9, P < 0.001).Conclusions:  In new school entrants, sleep problems are common and associated with poorer child mental health, health‐related quality of life and parent mental health. Future research needs to determine if systematically addressing sleep problems improves these outcomes.