bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Someone should oversee it’: patient perspectives on the ethical issues arising with the regulation of probiotics
Authors: Harrison Krista L. , Farrell Ruth M. , Brinich Margaret A. , Highland Janelle , Mercer MaryBeth , McCormick Jennifer B. , Tilburt Jon , Geller Gail , Marshall Patricia , Sharp Richard R. 
Published: December 2012

AbstractBackgroundAlthough many probiotic products are currently available in yogurt or pill form in the United States (US), there is uncertainty surrounding the structure of regulation of these products. As more therapeutic probiotics are developed, changes to existing regulatory process in the United States may be required to meet the needs of patients and users in the population.ObjectiveThis study examined how patients with chronic gastrointestinal (GI) diseases view the regulation of probiotics.DesignWe conducted a multi‐site qualitative study consisting of focus groups of patients with chronic gastrointestinal diseases at three tertiary hospitals: at [institutions removed for blinded review].ResultsWe conducted 22 focus groups with 136 patients with major gastrointestinal (GI) diseases between March and August 2009. Participants were not familiar with the existing regulation of probiotic products but wanted assurances of accurate labelling of strain as well as safety. Participants raised concerns that regulation of probiotics might be accompanied by greater costs, reduced access and increased involvement of pharmaceutical companies. Although participants voiced significant doubt of government regulators, they felt that products containing genetically modified probiotic strains should have oversight comparable to that of pharmaceutical drugs.Discussion and conclusionIf GI patient perspectives are indicative of public perceptions of therapeutic probiotics in the United States, consumers may expect more rigorous regulation in the future while simultaneously wanting low costs, easy access and low involvement of pharmaceutical companies. Manufacturers, translational scientists, clinicians and regulators should be sensitive to consumer attitudes when designing, testing and regulating new therapeutic probiotics.
Towards a stakeholders' consensus on patient payment policy: the views of health‐care consumers, providers, insurers and policy makers in six Central and Eastern European countries
Authors: Tambor Marzena , Pavlova Milena , Golinowska Stanisława , Sowada Christoph , Groot Wim 
Published: December 2012

AbstractBackgroundAlthough patient charges for health‐care services may contribute to a more sustainable health‐care financing, they often raise public opposition, which impedes their introduction. Thus, a consensus among the main stakeholders on the presence and role of patient charges should be worked out to assure their successful implementation.AimTo analyse the acceptability of formal patient charges for health‐care services in a basic package among different health‐care system stakeholders in six Central and Eastern European countries (Bulgaria, Hungary, Lithuania, Poland, Romania and Ukraine).MethodsQualitative data were collected in 2009 via focus group discussions and in‐depth interviews with health‐care consumers, providers, policy makers and insurers. The same participants were asked to fill in a self‐administrative questionnaire. Qualitative and quantitative data are analysed separately to outline similarities and differences in the opinions between the stakeholder groups and across countries.ResultsThere is a rather weak consensus on patient charges in the countries. Health policy makers and insurers strongly advocate patient charges. Health‐care providers overall support charges but their financial profits from the system strongly affects their approval. Consumers are against paying for services, mostly due to poor quality and access to health‐care services and inability to pay.ConclusionsTo build consensus on patient charges, the payment policy should be responsive to consumers' needs with regard to quality and equity. Transparency and accountability in the health‐care system should be improved to enhance public trust and acceptance of patient payments.
Merkel cell carcinoma with divergent differentiation: histopathological and immunohistochemical study of 15 cases with PCR analysis for Merkel cell polyomavirus
Authors: Martin Blanca , Poblet Enrique , Rios Juan Jose , Kazakov Dmitry , Kutzner Heinz , Brenn Thomas , Calonje Eduardo 
Published: December 2012

AimsTo report on 15 cases of Merkel cell carcinoma (MCC) with divergent differentiation, to characterize its clinicopathological spectrum and its relationship with Merkel cell polyomavirus (MCV).Methods and resultsFifteen patients with a mean age of 81 years were included. Follow‐up was available for 13 cases (range 12 days to 6 years; median 6 months). Recurrence, metastasis and mortality rates were 15.4%, 53.8% and 61.5%, respectively. All tumours showed the typical histological and immunohistochemical features of MCC, with at least one additional divergent component. Eight cases had a single aberrant component (squamous in six cases, follicular in one case, and porocarcinoma in one case), six cases had two aberrant components (squamous and sarcomatous in three cases, glandular and squamous in two cases, and sarcomatous and neuroblastic in one case), and one case had three aberrant components (glandular, squamous, and sarcomatous). All cases had dysplastic changes in the overlying epithelium, and four of 15 showed epidermotropism. PCR analysis for Merkel cell polyomavirus (MCV) gave negative results in all 12 cases tested.ConclusionsMerkel cell carcinoma with divergent differentiation is a highly aggressive tumour that might be difficult to recognize, owing to its wide histological variability. Negativity for MCV suggests that the virus is not implicated in the development of this subtype of MCC.
The effects of natural compounds‐containing mouthrinses on patients with fixed orthodontic appliance treatment: clinical and microbiological outcomes
Authors: Chen Yong , Wong Ricky W. K. , Seneviratne Chaminda Jayampath , Hagg Urban , McGrath Colman , Samaranayake Lakshman P. 
Published: December 2012

AimTo investigate the effects of two natural compounds‐containing mouthrinses (NCCMs) (a fructus mume (FM) extract–containing mouthrinse and an essential oil (EO)‐containing mouthrinse) on gingival health and microbial profiles in young orthodontic patients.DesignThis 6‐month randomized, single‐blinded, parallel‐controlled clinical trial consists of 90 patients with fixed appliance treatment. The subjects were allocated to (1) negative control group: oral hygiene instruction (OHI) alone; (2) test group 1: OHI plus EO mouthrinse; and (3) test group 2: OHI plus FM mouthrinse. Clinical examinations included plaque index (PI), bleeding index (BI) and modified gingival index (MGI). Salivary microbial quantifications included total aerobic and anaerobic bacteria, Streptococci and Lactobacilli counts. Clinical and microbiological examinations were conducted at baseline, 3rd and 6th months (T1, T2, and T3).ResultsBI was significantly reduced in both the FM mouthrinse and EO mouthrinse groups compared with the negative control group at T3 (P < 0.05). There were no significant intergroup differences in salivary bacteria counts in all groups (P > 0.05).ConclusionBoth NCCMs effectively reduced gingival bleeding without causing significant alterations of microbial profile in young orthodontic patients.
Modeling the global transmission of antiviral‐resistant influenza viruses
Authors: Chao Dennis L. 
Published: December 2012

Please cite this paper as: Chao. (2012) Modelling the global transmission of antiviral‐resistant influenza viruses. Influenza and Other Respiratory Viruses 7(Suppl. 1), 58–62.Background The mutations that confer resistance to antiviral agents are thought to be detrimental, or at best neutral, to influenza virus fitness. The fact that resistant influenza strains can circulate and sometimes replace sensitive strains is of great public health concern.Objectives We used mathematical modeling to test various hypotheses about the transmission of antiviral‐resistant influenza viruses by comparing the model’s output with the observed rise in antiviral resistance of seasonal A(H1N1) influenza viruses between 2006 and 2009.Methods We developed a mathematical model of the transmission of influenza among 321 cities around the globe. In the model, influenza strains resistant to antiviral agents competed with sensitive strains.Results and Conclusions We found that a resistant strain of influenza could not displace the sensitive strain as rapidly as has been observed unless it was more transmissible than the sensitive strain in the general population. We believe that an antiviral‐resistant strain displaced the antiviral‐sensitive seasonal A(H1N1) virus by hitchhiking on an escape mutation. Because of the complex global patterns of influenza circulation, tracking the emergence and spread of antiviral resistance must be a coordinated global effort.
Consequences of resistance: in vitro fitness, in vivo infectivity, and transmissibility of oseltamivir‐resistant influenza A viruses
Authors: Govorkova Elena A. 
Published: December 2012

Please cite this paper as: Govorkova EA. (2012) Consequences of resistance: in vitro fitness, in vivo infectivity, and transmissibility of oseltamivir‐resistant influenza A viruses. Influenza and Other Respiratory Viruses 7(Suppl. 1), 50–57.The development of drug resistance is a major drawback to any antiviral therapy, and the specific anti‐influenza drugs, the neuraminidase (NA) inhibitors (NAIs), are not excluded from this rule. The impact of drug resistance depends on the degree of reduction in fitness of the particular drug‐resistant virus. If the resistance mutations lead to only a modest biological fitness cost and the virus remains highly transmissible, the effectiveness of antiviral use is likely to be reduced. This review focuses on the fitness of oseltamivir‐resistant seasonal H1N1 and H3N2, 2009 pandemic H1N1 (H1N1pdm09), and highly pathogenic H5N1 influenza A viruses carrying clinically derived NAI resistance‐associated NA mutations.
Newer influenza antivirals, biotherapeutics and combinations
Authors: Hayden Frederick G. 
Published: December 2012

Please cite this paper as: Hayden FG. (2012) Newer Influenza Antivirals, Biotherapeutics and Combinations. Influenza and Other Respiratory Viruses 7(Suppl. 1), 63–75.This summary provides an overview of investigational antiviral agents for influenza and of future directions for development of influenza therapeutics. While progress in developing clinically useful antiviral agents for influenza has been generally slow, especially with respect to seriously ill and high‐risk patients, important clinical studies of intravenous neuraminidase inhibitors, antibodies and drug combinations are currently in progress. The current decade offers the promise of developing small molecular weight inhibitors with novel mechanisms of action, including host‐directed therapies, new biotherapeutics and drug combinations, that should provide more effective antiviral therapies and help mitigate the problem of antiviral resistance. Immunomodulatory interventions also offer promise but need to be based on better understanding of influenza pathogenesis, particularly in seriously ill patients. The development of combination interventions, immunomodulators and host‐directed therapies presents unique clinical trial design and regulatory hurdles that remain to be addressed.
Clinical use of approved influenza antivirals: therapy and prophylaxis
Authors: Ison Michael G. 
Published: December 2012

Please cite this paper as: Ison. (2012) Clinical use of approved influenza antivirals: therapy and prophylaxis. Influenza and Other Respiratory Viruses 7(Suppl. 1), 7–13.Currently, there are two commonly used classes of antiviral agents approved for the prevention of and treatment for influenza: the M2 Inhibitors (amantadine and rimantadine) and the neuraminidase inhibitors (oseltamivir, laninamivir, peramivir and zanamivir). These agents have been proven to be safe and effective alone or in combination for the treatment of uncomplicated influenza in otherwise healthy individuals. Although there are few prospective, randomized studies of these antivirals for the treatment of pregnant women, hospitalized patients, and immunocompromised patients infected with seasonal, pandemic, or avian H5N1 influenza, these agents are widely used for these indications. This article reviews the pharmacokinetics and clinical data available relative to the use of commercially available antiviral agents for the prevention of and treatment for influenza.
Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance
Authors: McKimm‐Breschkin Jennifer L. 
Published: December 2012

Please cite this paper as: McKimm‐Breschkin (2012) Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance. Influenza and Other Respiratory Viruses 7(Suppl. 1), 25–36.There are two major classes of antivirals available for the treatment and prevention of influenza, the M2 inhibitors and the neuraminidase inhibitors (NAIs). The M2 inhibitors are cheap, but they are only effective against influenza A viruses, and resistance arises rapidly. The current influenza A H3N2 and pandemic A(H1N1)pdm09 viruses are already resistant to the M2 inhibitors as are many H5N1 viruses. There are four NAIs licensed in some parts of the world, zanamivir, oseltamivir, peramivir, and a long‐acting NAI, laninamivir. This review focuses on resistance to the NAIs. Because of differences in their chemistry and subtle differences in NA structures, resistance can be both NAI‐ and subtype specific. This results in different drug resistance profiles, for example, the H274Y mutation confers resistance to oseltamivir and peramivir, but not to zanamivir, and only in N1 NAs. Mutations at E119, D198, I222, R292, and N294 can also reduce NAI sensitivity. In the winter of 2007–2008, an oseltamivir‐resistant seasonal influenza A(H1N1) strain with an H274Y mutation emerged in the northern hemisphere and spread rapidly around the world. In contrast to earlier evidence of such resistant viruses being unfit, this mutant virus remained fully transmissible and pathogenic and became the major seasonal A(H1N1) virus globally within a year. This resistant A(H1N1) virus was displaced by the sensitive A(H1N1)pdm09 virus. Approximately 0·5–1·0% of community A(H1N1)pdm09 isolates are currently resistant to oseltamivir. It is now apparent that variation in non‐active site amino acids can affect the fitness of the enzyme and compensate for mutations that confer high‐level oseltamivir resistance resulting in minimal impact on enzyme function.
Assays for monitoring susceptibility of influenza viruses to neuraminidase inhibitors
Authors: Okomo‐Adhiambo Margaret , Sheu Tiffany G. , Gubareva Larisa V. 
Published: December 2012

Please cite this paper as: Okomo‐Adhiambo et al. (2012) Assays for monitoring susceptibility of influenza viruses to neuraminidase inhibitors. Influenza and Other Respiratory Viruses 7(Suppl. 1), 44–49.Close monitoring of drug susceptibility among human influenza viruses was necessitated by widespread resistance to M2 inhibitors in influenza H1N1 (pre‐pandemic and 2009 pandemic) and H3N2 viruses, and of oseltamivir resistance in pre‐pandemic H1N1 viruses. The FDA‐approved neuraminidase (NA) inhibitors (NAIs), oseltamivir and zanamivir, as well as investigational NAIs, peramivir and laninamivir, are currently the principal treatment options for managing influenza infection. However, there are challenges associated with assessing virus susceptibility to this class of drugs. Traditional cell culture–based assays are not reliable for phenotypic testing of NAI susceptibility due to complexity in interpretation. Two types of laboratory assays are currently available for monitoring NAI susceptibility, phenotypic such as the neuraminidase inhibition (NI) assay and genotypic. The NI assay’s requirement for propagated virus lengthens testing turnaround; therefore, the need for timely detection of molecular markers associated with NAI resistance (e.g., H275Y in H1N1) has spurred the development of rapid, high‐throughput assays, such as real‐time RT‐PCR and pyrosequencing. The high sensitivity of genotypic assays allows testing of clinical specimens thus eliminating the need for virus propagation in cell culture. The NI assays are especially valuable when a novel virus emerges or a new NAI becomes available. Modifications continue to be introduced into NI assays, including optimization and data analysis criteria. The optimal assay of choice for monitoring influenza drug susceptibility varies widely depending on the needs of laboratories (e.g., surveillance purposes, clinical settings). Optimally, it is desirable to combine functional and genetic analyses of virus isolates and, when possible, the respective clinical specimens.
Genetic characterization of influenza virus circulating in Brazilian pigs during 2009 and 2010 reveals a high prevalence of the pandemic H1N1 subtype
Authors: Rajão Daniela S. , Costa Adrienny T. R. , Brasil Bruno S. A. F. , Del Puerto Helen L. , Oliveira Fernanda G. , Alves Fabiana , Braz Gissandra F. , Reis Jenner K. P. , Guedes Roberto M. C. , Lobato Zélia I. P. , Leite Rômulo C. 
Published: December 2012

BackgroundInfluenza A viruses circulating in pigs in Brazil are still not characterized, and only limited data are available about swine influenza epidemiology in the country. Therefore, we characterized the hemagglutinin (HA) and neuraminidase (NA) genes of influenza viruses isolated from Brazilian pigs. We also evaluated one case of probable swine‐to‐human transmission.MethodsTwenty influenza viruses isolated from pigs during 2009–2010 in five Brazilian states (Minas Gerais, Sao Paulo, Parana, Rio Grande do Sul, and Mato Grosso) were used. One human isolate, from a technician who became ill after visiting a swineherd going through a respiratory disease outbreak, was also used in the study. Phylogenetic analysis for the HA and NA genes and hemagglutinin amino acid sequence alignment were performed.ResultsAll isolates clustered with pandemic H1N1 2009 (pH1N1) viruses and appeared to have a common ancestor. Genetic diversity was higher in the HA than in the NA gene, and the amino acid substitution S203T in one of HA's antigenic sites was found in most of the samples. The human isolate was more related to swine isolates from the same herd visited by the technician than to other human isolates, suggesting swine‐to‐human transmission.ConclusionOur results show that pH1N1 was disseminated and the predominant subtype in Brazilian pigs in 2009–2010.
Perinatal brain injury, visual motor function and poor school outcome of regional low birth weight survivors at age nine
Authors: Zhang Jun , Mahoney Ashley Darcy , Pinto‐Martin Jennifer A 
Published: December 2012

Aims and objectivesTo explore the relationship between perinatal brain injury, visual motor function (VMF) and poor school outcome.BackgroundLittle is known about the status and underlying mechanism of poor school outcome as experienced by low birth weight survivors.DesignThis is a secondary data analysis.MethodsThe parental study recruited 1104 low birth weight (LBW) infants weighing ≤ 2000 g from three medical centres of Central New Jersey between 1984 and 1987. Seven hundred and seventy‐seven infants survived the neonatal period, and their developmental outcomes had been following up regularly until now. The development data of the survivors were used to achieve the research aims. Initial school outcome assessment was carried out in 9‐year‐old, using the Woodcock‐Johnson Academic Achievement Scale. The severity and range of perinatal brain injury was determined by repeated neonatal cranial ultrasound results obtained at 4 hours, 24 hours and 7 days of life.ResultsSeventeen and a half per cent of the sample experienced poor school performance at age 9 as defined by lower than one standard deviation (SD) of average performance score. Children with the most severe injury, PL/VE, had the lowest mathematics (F = 14·54, p = 0·000) and reading (anova results: F = 11·56, p = 0·000) performances. Visual motor function had a significant effect on children's overall school performance (Hotelling's trace value was 0·028, F = 3·414, p = 0·018), as well as subtest scores for reading (p = 0·006) and mathematics (p = 0·036). However, visual motor function was not a mediator in the association of perinatal brain injury and school outcome.ConclusionsPerinatal brain injury had a significant long‐term effect on school outcome.Relevance to clinical practiceLow birth weight infants with history of perinatal brain injury need be closely monitored to substantially reduce the rates of poor school outcome and other neurodevelopmental disabilities.
The Heterogeneous Thresholds Ordered Response Model: Identification and Inference
Authors: Peracchi Franco , Rossetti Claudio 
Published: December 2012

SummaryAlthough surveys routinely ask respondents to evaluate various aspects of their life on an ordered scale, there is concern about interpersonal comparability of these self- assessments. Statistically, the problem is one of identification in ordered response models with heterogeneous thresholds. As a solution to the identification problem, King and his colleagues proposed the use of anchoring vignettes, namely brief descriptions of hypothetical people or situations that survey respondents are asked to evaluate on the same scale as they use to rate their own situation. Although vignettes have been introduced in several social surveys and are increasingly employed in a variety of fields, the reliability of this approach hinges crucially on the validity of the assumptions of response consistency and vignette equivalence. The paper proposes a joint test of these key assumptions based on the fact that the underlying statistical model is overidentified if the two assumptions hold. Monte Carlo results show that the test proposed has good size and power properties in finite samples. We apply our test to self- assessment of pain by using data from the first wave of the Survey of Health, Ageing and Retirement in Europe. We find that, when using only one of the three available vignettes, or when the test is carried out separately by subgroups of respondents, the overidentifying restrictions are less likely to be rejected.
From Frontier to Bridgehead: Cross‐border Regions and the Experience ofYunnan,China
Authors: Su Xiaobo 
Published: December 2012

AbstractDrawing on recent theoretical tenets regarding cross‐border regions, this article analyzesChina's state spatial policies that aim to transformYunnan from a peripheral frontier into an economic bridgehead. The purposes of the present study are threefold: to contextualize the formation of Yunnan asChina's frontier; to examine why Yunnan has been strategically selected as a bridgehead to promoteChina's transnational economies; and to explore the central–provincial alliance as an innovative institutional arrangement and look at how this alliance can convertYunnan into a space of exception or new state space of development. This study finds that in order to convert regional assets into real competitiveness, theChinese state (national, provincial and local) emphasizes transnational cooperation, endeavors to maximize Yunnan's place‐specific locational advantages and promotes the differentiation of regional developmental trajectories acrossChina's national territory. The article contributes to studies of institutional arrangements for cross‐border cooperation in a non‐Western context and sheds light onChina's regional development policies in its hinterland.