bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Simple High-Performance Liquid Chromatography Method for Simultaneous Determination of Three Triazole Antifungals in Human Plasma
Authors: Zhang Mei , Moore Grant A. , Barclay Murray L. , Begg Evan J. 
Published: November 2012

ABSTRACT

A rapid and simple high-performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of three triazole antifungals (voriconazole, posaconazole, and itraconazole and the metabolite of itraconazole, hydroxyitraconazole) in human plasma. Sample preparation involved a simple one-step protein precipitation with 1.0 M perchloric acid and methanol. After centrifugation, the supernatant was injected directly into the HPLC system. Voriconazole, posaconazole, itraconazole, its metabolite hydroxyitraconazole, and the internal standard naproxen were resolved on a C
6
-phenyl column using gradient elution of 0.01 M phosphate buffer, pH 3.5, and acetonitrile and detected with UV detection at 262 nm. Standard curves were linear over the concentration range of 0.05 to 10 mg/liter (
r
2
> 0.99). Bias was <8.0% from 0.05 to 10 mg/liter, intra- and interday coefficients of variation (imprecision) were <10%, and the limit of quantification was 0.05 mg/liter.
Colistin Methanesulfonate and Colistin Pharmacokinetics in Critically Ill Patients Receiving Continuous Venovenous Hemodiafiltration
Authors: Karvanen Matti , Plachouras Diamantis , Friberg Lena E. , Paramythiotou Elisabeth , Papadomichelakis Evangelos , Karaiskos Ilias , Tsangaris Iraklis , Armaganidis Apostolos , Cars Otto , Giamarellou Helen 
Published: November 2012

ABSTRACT

This report describes the pharmacokinetics of colistin methanesulfonate (CMS) and colistin in five intensive care unit patients receiving continuous venovenous hemodiafiltration. For CMS, the mean maximum concentration of drug in plasma (
C
max
) after the fourth dose was 6.92 mg/liter and total clearance (CL) 8.23 liters/h. For colistin, the mean concentration was 0.92 mg/liter and CL/metabolized fraction (f
m
) 18.91 liters/h. Colistin concentrations were below the current MIC breakpoints, and the area under the concentration-time curve for the free, unbound fraction of the drug over 24 h in the steady state divided by the MIC (
f
AUC/MIC) was lower than recommended, suggesting that a dosage regimen of 160 mg CMS every 8 h (q8h) is inadequate.
Mechanism-Based Model of Parasite Growth and Dihydroartemisinin Pharmacodynamics in Murine Malaria
Authors: Patel Kashyap , Batty Kevin T. , Moore Brioni R. , Gibbons Peter L. , Bulitta Jürgen B. , Kirkpatrick Carl M. 
Published: November 2012

ABSTRACT

Murine models are used to study erythrocytic stages of malaria infection, because parasite morphology and development are comparable to those in human malaria infections. Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) models for antimalarials are scarce, despite their potential to optimize antimalarial combination therapy. The aim of this study was to develop a mechanism-based growth model (MBGM) for
Plasmodium berghei
and then characterize the parasiticidal effect of dihydroartemisinin (DHA) in murine malaria (MBGM-PK-PD). Stage-specific (ring, early trophozoite, late trophozoite, and schizont) parasite density data from Swiss mice inoculated with
Plasmodium berghei
were used for model development in S-ADAPT. A single dose of intraperitoneal DHA (10 to 100 mg/kg) or vehicle was administered 56 h postinoculation. The MBGM explicitly reflected all four erythrocytic stages of the 24-hour
P. berghei
life cycle. Merozoite invasion of erythrocytes was described by a first-order process that declined with increasing parasitemia. An efflux pathway with subsequent return was additionally required to describe the schizont data, thus representing parasite sequestration or trapping in the microvasculature, with a return to circulation. A 1-compartment model with zero-order absorption described the PK of DHA, with an estimated clearance and distribution volume of 1.95 liters h
−1
and 0.851 liter, respectively. Parasite killing was described by a turnover model, with DHA inhibiting the production of physiological intermediates (IC
50
, 1.46 ng/ml). Overall, the MBGM-PK-PD described the rise in parasitemia, the nadir following DHA dosing, and subsequent parasite resurgence. This novel model is a promising tool for studying malaria infections, identifying the stage specificity of antimalarials, and providing insight into antimalarial treatment strategies.
Emergence of Sequence Type 779 Methicillin-Resistant Staphylococcus aureus Harboring a Novel Pseudo Staphylococcal Cassette Chromosome
mec
(SCC
mec
)-SCC-SCC

CRISPR

Composite Element in Irish Hospitals
Authors: Kinnevey Peter M. , Shore Anna C. , Brennan Grainne I. , Sullivan Derek J. , Ehricht Ralf , Monecke Stefan , Slickers Peter , Coleman David C. 
Published: November 2012

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) has been a major cause of nosocomial infection in Irish hospitals for 4 decades, and replacement of predominant MRSA clones has occurred several times. An MRSA isolate recovered in 2006 as part of a larger study of sporadic MRSA exhibited a rare
spa
(t878) and multilocus sequence (ST779) type and was nontypeable by PCR- and DNA microarray-based staphylococcal cassette chromosome
mec
(SCC
mec
) element typing. Whole-genome sequencing revealed the presence of a novel 51-kb composite island (CI) element with three distinct domains, each flanked by direct repeat and inverted repeat sequences, including (i) a pseudo SCC
mec
element (16.3 kb) carrying
mecA
with a novel
mec
class region, a fusidic acid resistance gene (
fusC
), and two copper resistance genes (
copB
and
copC
) but lacking
ccr
genes; (ii) an SCC element (17.5 kb) carrying a novel
ccrAB4
allele; and (iii) an SCC element (17.4 kb) carrying a novel
ccrC
allele and a clustered regularly interspaced short palindromic repeat (CRISPR) region. The novel CI was subsequently identified by PCR in an additional 13 t878/ST779 MRSA isolates, six from bloodstream infections, recovered between 2006 and 2011 in 11 hospitals. Analysis of open reading frames (ORFs) carried by the CI showed amino acid sequence similarity of 44 to 100% to ORFs from
S. aureus
and coagulase-negative staphylococci (CoNS). These findings provide further evidence of genetic transfer between
S. aureus
and CoNS and show how this contributes to the emergence of novel SCC
mec
elements and MRSA strains. Ongoing surveillance of this MRSA strain is warranted and will require updating of currently used SCC
mec
typing methods.
Cholera Toxin Induces a Shift from Inactive to Active Cyclooxygenase 2 in Alveolar Macrophages Activated by Mycobacterium bovis BCG
Authors: Kogiso Mari , Shinohara Tsutomu , Dorey C. Kathleen , Shibata Yoshimi 
Published: November 2012

ABSTRACTIntranasal vaccination stimulates formation of cyclooxygenases (COX) and release of prostaglandin E2(PGE2) by lung cells, including alveolar macrophages. PGE2plays complex pro- or anti-inflammatory roles in facilitating mucosal immune responses, but the relative contributions of COX-1 and COX-2 remain unclear. Previously, we found thatMycobacterium bovisBCG, a human tuberculosis vaccine, stimulated increased release of PGE2by macrophages activatedin vitro; in contrast, intranasal BCG activated no PGE2release in the lungs, because COX-1 and COX-2 in alveolar macrophages were subcellularly dissociated from the nuclear envelope (NE) and catalytically inactive. This study tested the hypothesis that intranasal administration of BCG with cholera toxin (CT), a mucosal vaccine component, would shift the inactive, NE-dissociated COX-1/COX-2 to active, NE-associated forms. The results showed increased PGE2release in the lungs and NE-associated COX-2 in the majority of COX-2+macrophages. These COX-2+macrophages were the primary source of PGE2release in the lungs, since there was only slight enhancement of NE-associated COX-1 and there was no change in COX-1/COX-2 levels in alveolar epithelial cells following treatment with CT and/or BCG. To further understand the effect of CT, we investigated the timing of BCG versus CT administration forin vivoandin vitromacrophage activations. When CT followed BCG treatment, macrophagesin vitrohad elevated COX-2-mediated PGE2release, but macrophagesin vivoexhibited less activation of NE-associated COX-2. Our results indicate that inclusion of CT in the intranasal BCG vaccination enhances COX-2-mediated PGE2release by alveolar macrophages and further suggest that the effect of CTin vivois mediated by other lung cells.
Health expectancy in the occupied Palestinian territory: estimates from the Gaza Strip and the West Bank: based on surveys from 2006 to 2010
Authors: Qlalweh Khaled , Duraidi Mohammed , Brønnum-Hansen Henrik 
Published: November 2012

ObjectivesThe purpose of the study was to estimate health expectancy for the Palestinian population and to evaluate changes that have taken place over the past 5 years.DesignMortality data and population-based health surveys.SettingThe Israeli-occupied Palestinian territory of the Gaza Strip and the West Bank.Participants17 034 and 38 071 adults aged 20 or over participating the Palestinian Family Health Surveys of 2006 and 2010. Death rates for 2007 and 2010 covered the entire population.Outcome measuresLife expectancy and expected lifetime with and without chronic disease were estimated using the Sullivan method on the basis of mortality data and data on the prevalence of chronic disease.ResultsLife expectancy at the age of 20 increased from 52.8 years in 2006 to 53.3 years in 2010 for men and from 55.1 years to 55.7 years for women. In 2006, expected lifetime without a chronic disease was 37.7 (95% CI 37.0 to 38.3) years and 32.5 (95% CI 31.9 to 33.2) years for 20-year-old men and women, respectively. By 2010, this had decreased by 1.6 years for men and increased by 1.3 years for women. The health status of men has worsened. In particular, lifetime with hypertension and diabetes has increased. For women, the gain in life expectancy consisted partly of years with and partly of years without the most prevalent diseases.ConclusionsHealth expectancy for men and women diverged, which could to some extent be due to gender-specific exposures related to lifestyle factors and the impact of military occupation.
Partial sick leave associated with disability pension: propensity score approach in a register-based cohort study
Authors: Kausto Johanna , Solovieva Svetlana , Virta Lauri J , Viikari-Juntura Eira 
Published: November 2012

ObjectivesTo support sustainability of the welfare society enhanced work retention is needed among those with impaired work ability. Partial health-related benefits have been introduced for this target. The aim was to estimate the effects of partial sick leave on transition to disability pension applying propensity score methods.DesignRegister-based cohort study.SettingSample from the national sickness insurance registers representative of the Finnish working population (full-time workers) with long-term sickness absence due to musculoskeletal disorders, mental disorders, traumas or tumours.ParticipantsAll recipients of partial or full sickness benefit whose sick leave period had ended between 1 May and 31 December 2007 were included. The sample was limited to four most prevalent diagnostic groups—mental and musculoskeletal disorders, traumas and tumours. The total sample consisted of 1047 subjects on partial sick leave (treatment group) and 28 380 subjects on full sick leave (control group). A subsample (1017 and 25 249 subjects, respectively) was formed to improve the comparability of the two groups.Outcome measuresA three-category measure and a binary measure for the occurrence of disability pension on the last day of 2008 were computed.ResultsPartial sickness benefit reduced the risk (change in absolute risk) of full disability pension by 6% and increased the risk of partial disability pension by 8% compared with full sick leave. The effects did not differ markedly for the two main diagnostic groups of musculoskeletal and mental disorders. In men, the use of full disability pension was reduced by 10% with a 5% increase in the use of partial disability pension, while in women the effects were close to those of the total sample.ConclusionsOur findings suggest that combining work with partial sick leave may provide one means to increase work retention at population level. The use of partial sick leave could be encouraged among men.
Health effects following the Eyjafjallajökull volcanic eruption: a cohort study
Authors: Carlsen Hanne Krage , Hauksdottir Arna , Valdimarsdottir Unnur Anna , Gíslason Thorarinn , Einarsdottir Gunnlaug , Runolfsson Halldor , Briem Haraldur , Finnbjornsdottir Ragnhildur Gudrun , Gudmundsson Sigurdur , Kolbeinsson Thorir Björn , Thorsteinsson Throstur , Pétursdóttir Gudrun 
Published: November 2012

ObjectivesThe study aimed to determine whether exposure to a volcanic eruption was associated with increased prevalence of physical and/or mental symptoms.DesignCohort, with non-exposed control group.SettingNatural disasters like volcanic eruptions constitute a major public-health threat. The Icelandic volcano Eyjafjallajökull exposed residents in southern Iceland to continuous ash fall for more than 5 weeks in spring 2010. This study was conducted during November 2010–March 2011, 6–9 months after the Eyjafjallajökull eruption.ParticipantsAdult (18–80 years of age) eruption-exposed South Icelanders (N=1148) and a control population of residents of Skagafjörður, North Iceland (N=510). The participation rate was 72%.Main outcome measuresPhysical symptoms in the previous year (chronic), in the previous month (recent), General Health Questionnaire (GHQ-12) measured psychological morbidity.ResultsThe likelihood of having symptoms during the last month was higher in the exposed population, such as; tightness in the chest (OR 2.5; 95% CI 1.1 to 5.8), cough (OR 2.6; 95% CI 1.7 to 3.9), phlegm (OR 2.1; 95% CI 1.3 to 3.2), eye irritation (OR 2.9; 95% CI 2.0 to 4.1) and psychological morbidity symptoms (OR 1.3; 95% CI 1.0 to 1.7). Respiratory symptoms during the last 12 months were also more common in the exposed population; cough (OR 2.2; 95% CI 1.6 to 2.9), dyspnoea (OR 1.6; 95% CI 1.1 to 2.3), although the prevalence of underlying asthma and heart disease was similar. Twice as many in the exposed population had two or more symptoms from nose, eyes or upper-respiratory tract (24% vs 13%, p<0.001); these individuals were also more likely to experience psychological morbidity (OR 4.7; 95% CI 3.4 to 6.5) compared with individuals with no symptoms. Most symptoms exhibited a dose–response pattern within the exposed population, corresponding to low, medium and high exposure to the eruption.Conclusions6–9 months after the Eyjafjallajökull eruption, residents living in the exposed area, particularly those closest to the volcano, had markedly increased prevalence of various physical symptoms. A portion of the exposed population reported multiple symptoms and may be at risk for long-term physical and psychological morbidity. Studies of long-term consequences are therefore warranted.
Is thiazolidinediones use a factor in delaying the need for insulin therapy in type 2 patients with diabetes? A population-based cohort study
Authors: Carney Greg A , Bassett Ken , Wright James M , Dormuth Colin R 
Published: November 2012

ObjectiveTo understand the independent role of thiazolidinediones (TZDs) in delaying progression to parenteral insulin therapy.DesignPopulation-based retrospective cohort study.SettingBritish Columbia, Canada.ParticipantsA total of 18 867 type 2 diabetes patients (mean age 58.9) treated with metformin as first-line therapy who then switched or added a TZD or sulphonylurea as a second-line treatment between 1 January 1998 and 31 March 2008.Outcome measuresMultivariable Poisson regression models were used to estimate the effect of using TZD compared to sulphonylureas on time to the initiation of insulin treatment (third-line).ResultsThe adjusted rate difference in women aged <60 showed 2.22 fewer insulin initiation events per 100 person-years (PYs) in the TZD group versus the sulphonylurea group (95% CI −3.46 to −0.99). Men in the same age group had 1.50 fewer insulin initiation events per 100 PYs in the TZD group versus the sulphonylurea group (95% CI −2.44 to −0.56). The average time in days to initiation on insulin in the sulphonylurea, rosiglitazone and pioglitazone group was 343, 252 and 339, respectively. The cumulative hazard for starting insulin for sulphonylurea patients at 12, 24, 36 and 48 months was approximately three times higher compared to TZD patients.ConclusionsSecond-line TZD therapy compared to second-line sulphonylurea therapy was associated with a lower incidence of insulin initiation as third-line treatment in patients with type 2 diabetes, with a mean delay of 90 days. This duration of delay must be weighed against the absence of a proven reduction in morbidity or mortality with TZDs and their known serious cardiovascular harm.
Long-term impact of pregnancy-related venous thrombosis on quality-of-life, general health and functioning: results of a cross-sectional, case–control study
Authors: Wik Hilde Skuterud , Jacobsen Anne Flem , Sandvik L , Sandset P M 
Published: November 2012

ObjectivesTo evaluate the long-term consequences of pregnancy-related venous thrombosis (VT) by the assessment of generic quality-of-life (QOL), well-being, general health and daily-life functioning. We also wanted to evaluate the impact of the frequently occurring complication post-thrombotic syndrome (PTS) after that of deep vein thrombosis (DVT).DesignPopulation-based cross-sectional, case–control study.Setting18 Norwegian hospitals during 1990–2003.ParticipantsThe study population comprised 559 cases with a validated first-ever, pregnancy-related VT and 1229 controls naïve for VT at the time of index pregnancy. Cases were identified using the Norwegian Patient Register and the Medical Birth Registry of Norway and the latter was used to select as controls women who gave birth at the same time as a case. After exclusion of two cases with missing location of VT, the final study population comprised 311 cases and 353 controls.MethodsSelf-completion of a comprehensive questionnaire in 2006.Main outcome measuresGeneric QOL and well-being assessed by the Ferrans and Powers QOL Index (QLI) and the General Health Questionnaire (GHQ-20).ResultsQOL assessed by QLI did not differ between cases and controls; mean score 23.1 (95% CI 22.7 to 23.5) vs 23.7 (23.3 to 24.0), neither did well being assessed by GHQ-20; 18.7 (18.0 to 19.4) vs 17.9 (17.3 to 18.4). However, cases reported pain other than in the lower limbs and muscle–skeletal problems more often and were more often physically worn out after work compared with controls. Cases which developed PTS reported poorer health, had pain more often, developed skin and psychiatric problems, used analgesic drugs more frequently and were more often on sick leave as compared to those without PTS.ConclusionsLong-term generic QOL and subjective well-being 3–16 years after a pregnancy-related VT were not different from a reference population, but women with PTS after DVT seemed to have poorer QOL and an impaired general health.
Psychosocial care for persons affected by emergencies and major incidents: a Delphi study to determine the needs of professional first responders for education, training and support
Authors: Drury John , Kemp Verity , Newman Jonathan , Novelli David , Doyle Christopher , Walter Darren , Williams Richard 
Published: November 2012

BackgroundThe role of ambulance clinicians in providing psychosocial care in major incidents and emergencies is recognised in recent Department of Health guidance. The study described in this paper identified NHS professional first responders’ needs for education about survivors’ psychosocial responses, training in psychosocial skills, and continuing support.MethodAmbulance staff participated in an online Delphi questionnaire, comprising 74 items (Round 1) on 7-point Likert scales. Second-round and third-round participants each received feedback based on the previous round, and responded to modified versions of the original items and to new items for clarification.ResultsOne hundred and two participants took part in Round 1; 47 statements (64%) achieved consensus. In Round 2, 72 people from Round 1 participated; 15 out of 39 statements (38%) achieved consensus. In Round 3, 49 people from Round 2 participated; 15 out of 27 statements (59%) achieved consensus. Overall, there was consensus in the following areas: ‘psychosocial needs of patients’ (consensus in 34/37 items); ‘possible sources of stress in your work’ (8/9); ‘impacts of distress in your work’ (7/10); ‘meeting your own emotional needs’ (4/5); ‘support within your organisation’ (2/5); ‘needs for training in psychosocial skills for patients’ (15/15); ‘my needs for psychosocial training and support’ (5/6).ConclusionsAmbulance clinicians recognise their own education needs and the importance of their being offered psychosocial training and support. The authors recommend that, in order to meet patients’ psychosocial needs effectively, ambulance clinicians are provided with education and training in a number of skills and their own psychosocial support should be enhanced.
The use of non-standard motorcycle helmets in low- and middle-income countries: a multicentre study
Authors:   Road Traffic Injuries Research Network Multicenter Study Collaborators, Ackaah Williams , Afukaar Francis , Agyemang Williams , Thuy Anh Trinh , Hejar A R , Abdul Ghaffar , Gururaj Gopalkrishna , Elisa Hidalgo-Solórzano , Martha Híjar , Hyder Adnan A , Inclán-Valadez Cristina , Kulanthayan Subramaniam , Norton Robyn , Odero Wilson , Owoaje Eme T , Peden Margie , Rajam Krishnan , Abdul Razzak Junaid , Oluwafunmilola Sangowawa Adesola , Shah Jawaid , Le Tuan Pham , Umar RS Radin , Thi Van Anh Nguyen , Van der Putten Marc , Vajanapoom Nitaya , Vichit-Vadakan Nuntavarn , Yellappan Kaviyarasu , Yu James 
Published: November 2012

BackgroundThe use of non-standard motorcycle helmets has the potential to undermine multinational efforts aimed at reducing the burden of road traffic injuries associated with motorcycle crashes. However, little is known about the prevalence or factors associated with their use.MethodsCollaborating institutions in nine low- and middle-income countries undertook cross-sectional surveys, markets surveys, and reviewed legislation and enforcement practices around non-standard helmets.Findings5563 helmet-wearing motorcyclists were observed; 54% of the helmets did not appear to have a marker/sticker indicating that the helmet met required standards and interviewers judged that 49% of the helmets were likely to be non-standard helmets. 5088 (91%) of the motorcyclists agreed to be interviewed; those who had spent less than US$10 on their helmet were found to be at the greatest risk of wearing a non-standard helmet. Data were collected across 126 different retail outlets; across all countries, regardless of outlet type, standard helmets were generally 2–3 times more expensive than non-standard helmets. While seven of the nine countries had legislation prohibiting the use of non-standard helmets, only four had legislation prohibiting their manufacture or sale and only three had legislation prohibiting their import. Enforcement of any legislation appeared to be minimal.InterpretationOur findings suggest that the widespread use of non-standard helmets in low- and middle-income countries may limit the potential gains of helmet use programmes. Strategies aimed at reducing the costs of standard helmets, combined with both legislation and enforcement, will be required to maximise the effects of existing campaigns.