bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical significance of drug–drug interactions in the era of direct‐acting anti‐viral agents against chronic hepatitis C
Authors: Maasoumy B. , Port K. , Calle Serrano B. , Markova A. A. , Sollik L. , Manns M. P. , Cornberg M. , Wedemeyer H. 
Published: October 2013

SummaryBackgroundDrug–drug interactions (DDIs) in the treatment of chronic hepatitis C infection became a potential challenge with the introduction of direct‐acting anti‐virals (DAAs). Both currently approved DAAs, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), are substrates and inhibitors of P‐glycoprotein and the cytochrome P450 3A4, which are regularly involved in DDIs.AimTo analyse the risk for DDIs in patients with chronic HCV genotype 1 infection considered for PI treatment at a tertiary referral centre.MethodsThe first 115 consecutive patients selected for a PI therapy at Hannover Medical School were included. All changes to co‐medication before and during PI treatment were documented. Drugs were checked for DDIs with TVR and BOC using DDI websites and the respective prescribing information.ResultsOut‐patient medication contained 116 different drugs. Median number of drugs/patient was 2 (range 0–11). The risk for DDIs was substantial for 38% of the drugs affecting 49% of patients. Only 4% of the drugs were strictly contraindicated. DDIs between a PI and drugs newly prescribed during anti‐viral therapy were considerable in 42% of the patients. Suspected DDIs were managed by dose adjustments and discontinuation of co‐medication in 7% and 21% of the patients respectively.ConclusionsMany patients with chronic HCV genotype 1 infection are affected by potential DDIs if treated with a protease inhibitor, but only in a minority of cases co‐medication is strictly incompatible. Overall, the challenge of DDIs is time‐consuming, but well manageable by a careful review of the patient's drug chart and monitoring during treatment.
Rates and predictors of response to anti‐viral treatment for hepatitis C virus inHIV/HCVco‐infection in a nationwide study of 619 patients
Authors: Ioannou G. N. , Scott J. D. , Yang Y. , Green P. K. , Beste L. A. 
Published: October 2013

SummaryBackgroundThe effectiveness of anti‐viral treatment for hepatitis C virus (HCV) inHIV/HCVco‐infected patients in ‘real world’, clinical practice is unclear.AimsTo determine the rates and predictors of sustained virological response (SVR) to anti‐viral treatment forHCVwith pegylated interferon (PEG‐IFN) and ribavirin inHIV/HCVco‐infected patients.MethodsWe identified allHIV/HCVco‐infected patients who received anti‐viral treatment with PEG‐IFN and ribavirin in the Veterans Affairs healthcare system nationally between 2002 and 2009 (n = 665).ResultsSustained virological response was achieved in 21.6% overall, 16.7% among patients with genotype 1HCV(n = 491) and 44% among patients with genotype 2 or 3HCV(n = 116). Among genotype 1‐infected patients, characteristics that were negatively associated withSVRindependently included baselineHCVviral load >2 million IU/mL [adjusted odds ratio (AOR) 0.41, 95%CI0.2–0.7], Black race [AOR0.56 (0.3–0.96)], diabetes [AOR0.42 (0.2–0.9)], baseline anaemia [AOR0.42 (0.2–0.97)], serum aspartate aminotransferase/alanine aminotransferase ratio ≥1.2 [AOR0.48 (0.2–0.97)] and use of zidovudine [AOR0.41 (0.2–0.9)]; characteristics positively associated withSVRincluded a starting dose of ribavirin ≥1000–1200 mg/day [AOR2.0 (1.1–3.7)] and erythropoietin use during treatment [AOR2.9 (1.6–5.0)]. Among genotype 2 or 3 infected patients, only erythropoietin use was an independent predictor ofSVR[AOR3.1 (1.2–7.8)], while a starting dose of ribavirin >800 mg/day was not associated withSVR.ConclusionsSustained virological response rates achieved with PEG‐IFN and ribavirin inHIV/HCVco‐infected patients are low in clinical practice. The use of erythropoietin was the most important, modifiable factor associated withSVR.
Patients with prostate cancer continue to have excess mortality up to 15 years after diagnosis
Authors: Husson Olga , van Steenbergen Liza N. , Koldewijn Evert L. , Poortmans Philip M. , Coebergh Jan Willem W. , Janssen‐Heijnen Maryska L.G. 
Published: October 2013

Objective
To estimate the population‐based conditional 5‐year relative survival rates for patients with prostate cancer (PCa).
Patients and Methods
All 98 672 patients, aged 45–89 years, diagnosed in the Netherlands with PCa (clinical T stage 1–4) in the period 1989–2008 were selected from the Netherlands Cancer Registry and followed up until 2010.
The conditional 5‐year relative survival rate was estimated for every subsequent year of survival up to 15 years after diagnosis.
Results
The conditional 5‐year relative survival rate decreased with survival time from diagnosis. Excess mortality (conditional 5‐year relative survival rate <95%) for patients with clinical T1 stage only became manifest 5 years after diagnosis and increased to almost 10% after 10 years.
Patients with more advanced disease (cT2–cT4) were found to have an excess mortality rate of 6–12% at diagnosis, which increased to 15–22% after 10 years. Excess mortality occurred earlier for the older age groups.
The 5‐year relative survival rate at diagnosis was <90% for all age groups of patients with cT3/cT4 disease and excess mortality for this group increased to >20% for those who had already survived for 5 years since diagnosis.
Conclusions
Patients with PCa were found to have excess mortality within 10 years of diagnosis. Excess mortality was found at an earlier timepoint for patients with a more advanced stage and for older age groups.
Quantitative insight into conditional survival is useful for caregivers to help plan optimum cancer treatment and surveillance and to inform patients about their actual prognosis during follow‐up, taking the current condition of the patient into account.
Quality of life and associated factors in persons with chronic rhinosinusitis in the general population: A prospective questionnaire and clinical cross‐sectional study
Authors: Lange B. , Holst R. , Thilsing T. , Baelum J. , Kjeldsen A. 
Published: October 2013

ObjectivesThe European Position Paper on Rhinosinusitis and Nasal Polyps describes methods to perform population‐based and clinical studies on chronic rhinosinusitis in a standardised way, and it also describes how to clinical investigate CRS. The aim of this cross‐sectional study was to evaluate quality of life and objective findings in persons with chronic rhinosinusitis recruited from the general population.DesignAs part of a trans‐European study, selected respondents to a survey questionnaire were invited for a clinical visit. Subjective symptoms and rhinoscopy were used for the clinical diagnosis of chronic rhinosinusitis, and persons with and without chronic rhinosinusitis were compared.SettingThis research took place in the department of Otolaryngology, Odense University Hospital.ParticipantsA total of 366 persons participated at the clinical visit, and of these, 91 were diagnosed with chronic rhinosinusitis, 271 without chronic rhinosinusitis and four persons were excluded.Main outcome measuresSeverity of symptoms and disease‐specific quality of life were measured using the Sino‐Nasal Outcome Test 22, and generic quality of life was measured using European quality of life – 5 dimensions including an index score and a visual analogue scale.ResultsThe prevalence of chronic rhinosinusitis was 9%, and the prevalence of polyps was 4%. Persons with chronic rhinosinusitis had significantly reduced disease‐specific quality of life (P = 0.00) and generic quality of life (P = 0.04 and 0.01) compared with persons without chronic rhinosinusitis. Having chronic rhinosinusitis was correlated to age, allergic rhinitis and smell.ConclusionThis study gives insight into health‐related quality of life and objective findings in persons with chronic rhinosinusitis recruited from the general population.
Optimal plane for nerve sparing total mesorectal excision, immunohistological study and 3D reconstruction: an embryological study
Authors: Bertrand M. M. , Alsaid B. , Droupy S. , Benoit G. , Prudhomme M. 
Published: October 2013

AbstractAimGenito‐urinary complications are frequent after rectal surgery and are often due to nerve damage. The relationship between the pelvic nerves and surgical planes are unclear. The aim of the study was to determine the relationship between the inferior hypogastric plexus and the fascia of the lateral pelvic wall and between Denonvilliers’ fascia and the efferent branches of the inferior hypogastric plexus.MethodComputer‐assisted anatomical dissection was used. Serial histological sections were made from six human foetuses and a male adult. Sections were stained with haematoxylin and eosin, Masson's trichrome and immunostainings. The sections were then digitalized and reconstructed in three dimensions.ResultsThe inferior hypogastric plexus was situated in a virtual space between the fascia propria of the rectum and the fascia on the upper surface of the levator ani. During the lateral dissection, the optimal surgical plane is the plane of the fascia propria of the rectum. We located Denonvilliers’ fascia in three dimensions. It plays the role of a protective sheet for the neurovascular bundle. The optimal plane for nerve preservation is situated behind Denonvilliers’ fascia.ConclusionThis study has enabled a clear visualization of the optimal planes to perform total mesorectal excision while ensuring nerve preservation. Three‐dimensional visualization clearly helps to bridge the gap between histological examination and the findings of surgery.
Utility and pattern of positivity of p40 in the diagnosis of squamous cell carcinoma of the lung by cytology: the first study on fine needle aspiration smears
Authors: Jain D. , Mathur S. R. , Guleria R. , Iyer V. K. 
Published: October 2013

ObjectiveImmunohistochemistry for p40 has emerged as a clinically applicable tool with high sensitivity and specificity to distinguish lung adenocarcinoma and squamous cell carcinoma (SCC). It appears to be an excellent marker for squamous differentiation. Although application of p40 in cell blocks has been reported, its expression has not been described in cytology smears. The aim was to study the expression of p40 in fine needle aspirates of SCC of the lung and to analyse differences in immunoreactivity in variably differentiated SCC.MethodsThe study used aspirates of lung masses diagnosed as SCC over a period of 2 years. p40 immunocytochemistry was performed on destained Papanicolaou smears. Nuclear staining was semi‐quantitatively evaluated as 0, 1 + , 2 + and 3 + based on the percentage positivity of tumour cells and was correlated with differentiation of the tumour. Adequate unmatched histology (50 biopsies) and cytology (25 smears) controls were taken for comparison.ResultsA total of 45 cases of primary and five cases of metastatic pulmonary SCC were identified. There were 17 well, 24 moderately and nine poorly differentiated SCC. p40 immunoreactivity was 2–3 + in all moderate and poorly differentiated tumours, however, negative to 1 + in all well‐differentiated carcinomas (P < 0.0001).Conclusionp40 immunostain is a valuable stain in identifying lung SCCs and works well in aspiration smears. The pattern of positivity varies with the differentiation of the tumour and is seen prominently in higher grade SCC where in practice the need arises for distinguishing them from either poorly differentiated adenocarcinomas or non‐small cell carcinoma, not otherwise specified.
Gender‐Related Changes of the Epicardial Fat Thickness and Leptin in Obstructive Sleep Apnea
Authors: Akilli Hakan , Kayrak Mehmet , Bekci Taha Tahir , Erdogan Halil İbrahim , Aribas Alpay , Yildirim Oguzhan , Taner Alpaslan , Erer Murat , Unlu Ali 
Published: October 2013

BackgroundEpicardial fat thickness (EFT), an indicator of visceral obesity, and leptin are 2 novel markers for studying the obstructive sleep apnea (OSA) population. This study aimed to investigate the effects of gender on leptin levels and EFT, and the relation with OSA severity.MethodsA total of 149 patients with OSA (female/male 55/94 and mean age 50.8 ± 9.2 years) and 50 control patients (female/male 24/26 and mean age 48.9 ± 8.8 years) were included in the study. The study population was divided into 4 groups according to apnea/hypopnea index (AHI) as control (AHI <5), the mild OSA (AHI 5–14), the moderate OSA (AHI 15–29), and the severe OSA (AHI ≥30). EFT was obtained from parasternal long‐axis and parasternal short‐axis echocardiographic images.ResultsLeptin levels among females were significantly higher than among males (10.5 [7.8] vs. 5.4 [4.5] ng/mL, P = 0.001, respectively). Among women, leptin levels were significantly higher in the severe OSA group compared to the control group (9.8 [9.0] vs. 15.5 [10.1] ng/mL, P = 0.05, respectively). Conversely, no relation was observed between OSA severity and the leptin levels among men. EFT was not significantly different between the 2 genders (P > 0.05). EFT was thicker in the severe OSA group than in the control and mild OSA groups among women, whereas EFT was not changed according to OSA severity among males (P > 0.05).ConclusionLeptin and EFT may be a valuable parameter in the evaluation of OSA severity in women than in men.
Is MC1 dispensable for regulation of cutaneous inflammatory and immune responses?
Authors: Böhm Markus , Luger Thomas A. , Steingräber Annika K. , Goerge Tobias 
Published: October 2013

AbstractThe melanocortin‐1 receptor (MC1) – being most abundantly expressed in the skin by melanocytes – has a physiological role for melanin pigmentation in many vertebrate species. MC1 has also been implicated in regulation of skin inflammation as this receptor is detectable in the majority of non‐melanocytic cell types and its ligand α‐melanocyte‐stimulating hormone (α‐MSH) exerts immunoregulatory and anti‐inflammatory effects. However, in vivo studies on mice with targeted disruption of MC1 have been missing in the context of skin inflammation until recently. Wolnicka‐Glubisz et al. now reported that the course of ultraviolet (UV)‐induced inflammation, contact hypersensitivity, neonatal immune tolerance and UV‐induced immunosuppression is similar in MC1 signal‐deficient (C57BL/6‐Mc1re/e) and wild‐type mice. These unexpected findings are supported by own observations in experimentally induced immune‐complex‐mediated vasculitis: Mc1re/e mice exhibited a similar extent of the reverse passive cutaneous Arthus reaction compared with wild‐type animals. Future studies are thus needed to clarify whether these findings are due to limitations in the chosen mouse model and/or point to additional MC subtypes that may regulate inflammatory and immune responses in the skin.
A non‐coding mutation in the 5′ untranslated region of patched homologue 1 predisposes to basal cell carcinoma
Authors: Tietze Julia K. , Pfob Martina , Eggert Marlene , von Preußen Anna , Mehraein Yasmin , Ruzicka Thomas , Herzinger Thomas 
Published: October 2013

AbstractMutations in the human homolog of the Drosophila patched gene, patched homologue 1 (PTCH‐1), are responsible for most hereditary and sporadic basal cell carcinomas. Here, we present a father and daughter with a high propensity for the development of basal cell carcinoma who were heterozygous for a non‐coding germline mutation in the 5′ untranslated region (UTR) of PTCH‐1 (insertion of a surplus CGG triplet at the site of a seven times CGG repeat). We analysed the impact of this mutation on PTCH translation using a luciferase‐based reporter vector. Insertion of an eighth CGG in the 5′ UTR repressed protein translation dramatically when compared to the wild‐type sequence. Our results suggest that this non‐coding variant in the 5′ UTR represents a mutation predisposing to basal cell carcinoma.
High‐frequency fire alters C : N : P stoichiometry in forest litter
Authors: Toberman Hannah , Chen Chengrong , Lewis Tom , Elser James J 
Published: October 2013

AbstractFire is a major driver of ecosystem change and can disproportionately affect the cycling of different nutrients. Thus, a stoichiometric approach to investigate the relationships between nutrient availability and microbial resource use during decomposition is likely to provide insight into the effects of fire on ecosystem functioning. We conducted a field litter bag experiment to investigate the long‐term impact of repeated fire on the stoichiometry of leaf litter C, N and P pools, and nutrient‐acquiring enzyme activities during decomposition in a wet sclerophyll eucalypt forest in Queensland, Australia. Fire frequency treatments have been maintained since 1972, including burning every 2 years (2yrB), burning every 4 years (4yrB) and no burning (NB). C : N ratios in freshly fallen litter were 29–42% higher and C : P ratios were 6–25% lower for 2yrB than NB during decomposition, with correspondingly lower 2yrB N : P ratios (27–32) than for NB (34–49). Trends in litter soluble and microbial N : P ratios were similar to the overall litter N : P ratios across fire treatments. Consistent with these, the ratio of activities for N‐acquiring to P‐acquiring enzymes in litter was higher for 2yrB than NB, whereas 4yrB was generally intermediate between 2yrB and NB. Decomposition rates of freshly fallen litter were significantly lower for 2yrB (72 ± 2% mass remaining at the end of experiment) than for 4yrB (59 ± 3%) and NB (62 ± 3%), a difference that may be related to effects of N limitation, lower moisture content, and/or litter C quality. Results for older mixed‐age litter were similar to those for freshly fallen litter although treatment differences were less pronounced. Overall, these findings show that frequent fire (2yrB) decoupled N and P cycling, as manifested in litter C : N : P stoichiometry and in microbial biomass N : P ratio and enzymatic activities. Furthermore, these data indicate that fire induced a transient shift to N‐limited ecosystem conditions during the postfire recovery phase.
Autumn warming reduces the CO2 sink of a black spruce forest in interior Alaska based on a nine‐year eddy covariance measurement
Authors: Ueyama Masahito , Iwata Hiroki , Harazono Yoshinobu 
Published: October 2013

AbstractNine years (2003–2011) of carbon dioxide (CO2) flux were measured at a black spruce forest in interior Alaska using the eddy covariance method. Seasonal and interannual variations in the gross primary productivity (GPP) and ecosystem respiration (RE) were associated primarily with air temperature: warmer conditions enhanced GPP and RE. Meanwhile, interannual variation in annual CO2 balance was controlled predominantly by RE, and not GPP. During these 9 years of measurement, the annual CO2 balance shifted from a CO2 sink to a CO2 source, with a 9‐year average near zero. The increase in autumn RE was associated with autumn warming and was mostly attributed to a shift in the annual CO2 balance. The increase in autumn air temperature (0.22 °C yr−1) during the 9 years of study was 15 times greater than the long‐term warming trend between 1905 and 2011 (0.015 °C yr−1) due to decadal climate oscillation. This result indicates that most of the shifts in observed CO2 fluxes were associated with decadal climate variability. Because the natural climate varies in a cycle of 10–30 years, a long‐term study covering at least one full cycle of decadal climate oscillation is important to quantify the CO2 balance and its interaction with the climate.
Tooth loss, chewing efficiency and cognitive impairment in geriatric patients
Authors: Elsig Fanny , Schimmel Martin , Duvernay Elena , Giannelli Sandra V. , Graf Christoph E. , Carlier Sabrina , Herrmann François R. , Michel Jean‐Pierre , Gold Gabriel , Zekry Dina , Müller Frauke 
Published: October 2013

BackgroundPatients with dementia have poorer oral health and fewer teeth than their peers without cognitive impairment.ObjectiveThe hypothesis of this study is that the number of natural teeth and the chewing efficiency are associated with cognitive functioning.MethodsThis cross‐sectional study included 29 patients diagnosed with dementia aged 75 years or older and 22 controls who were either cognitively normal (n = 19) or with mild cognitive impairment (n = 3). Neuropsychological, nutritional and dental assessments were performed. The chewing efficiency was evaluated with a two‐colour mixing test.ResultsDemented patients and controls presented with a mean of 4.9 and 6.5 teeth, respectively (n.s.). The number of natural teeth was not associated with dementia (p = 0.553). Same results were found for age (p = 0.746) and sex (p = 0.901). The chewing efficiency by visual inspection proved worse in participants with dementia than in the controls (p < 0.011) and explained 9.3% of the variance in the diagnosis of dementia. Neither dental state nor chewing efficiency was related to the nutritional state.ConclusionChewing efficiency seems stronger associated with cognitive impairment than the number of teeth. Hence, in a more holistic approach for the geriatric assessment, the dental examination may be complemented by a chewing efficiency test.
The Social Protection Floors Recommendation, 2012 (No. 202): Can a six‐page document change the course of social history?
Authors: Cichon Michael 
Published: October 2013

AbstractIn June 2012, the global community made an important step to firmly establish social protection as part of national and global development strategies. The International Labour Conference unanimously adopted the Recommendation concerning national floors of social protection, 2012 (No. 202), providing concrete content to the human right to social security. This article puts the Recommendation into its historical standard setting and development policy context, reviews the emergence of the social protection floor concept, and analyses the contents of the new Recommendation and some of its political hotspots. It then explores whether the new instrument has the potential to change the social reality in the 185 ILO member States. It concludes that its adoption is an unprecedented demonstration of good will and far‐reaching global social policy consensus. However, in order to help create space for national policy change, the campaign to achieve at least a minimum of social security for all needs to continue and has to be kept on the international agenda. In closing, the article lists strategies that the global coalition behind this campaign needs to pursue for social security to remain or become an inalienable objective in national and international development strategies.
Financing social protection floors: Considerations of fiscal space
Authors: Harris Elliott 
Published: October 2013

AbstractThe effectiveness of social protection in combating poverty and vulnerability, cushioning shocks, attenuating inequality, and supporting long‐term growth is well‐established, but effective social protection systems have long been seen as an unaffordable luxury in many developing and low‐income countries. The social protection floor concept aims at providing a guaranteed minimum of social protection at a reasonable cost, even in resource‐constrained circumstances, serving as a platform for the gradual implementation of a full social protection system. Introducing and maintaining or extending the floor requires the mobilization of fiscal space, both immediately and in the future. The article argues that efforts to generate fiscal space must carefully consider issues of predictability, as well as the impact of present funding choices on fiscal and debt sustainability, macroeconomic stability, inequality, poverty reduction and growth, and hence on future fiscal space. It examines from this perspective some of the implications of generating fiscal space through additional domestic resource mobilization, expenditure reallocation or efficiency gains, reduction of debt service, or external funding. The article also presents some evidence of a wide range of recent interventions that have been financed at reasonable cost on a sustainable basis in countries at different levels of income and development, using both own resources and external funds.