bluuebunny/crossref_metadata_2025_split huggingface dataset:
Micrographia and related deficits in Parkinson's disease: a cross-sectional study
Authors: Wagle Shukla Aparna , Ounpraseuth Songthip , Okun Michael S , Gray Vickie , Schwankhaus John , Metzer Walter Steven 
Published: June 2012

ObjectivesTo determine the prevalence and clinical features associated with micrographia in Parkinson's Disease (PD).SettingThis study was conducted at a Movement Disorders clinic located in a Veteran Administration Hospital.ParticipantsPD subjects were included only if they satisfied UK Parkinson's Disease Society criteria for diagnosis. Subjects with history of severe tremors, dystonia, dyskinesia, strokes, peripheral neuropathy and dementia were excluded.DesignThis was a case–control study where PD subjects were prospectively enrolled and their demographics, Hoehn & Yahr stage, Unified Parkinson's Disease Rating Scale and Mini Mental Status examination (MMSE) scores were recorded. All subjects were specifically asked for micrographia on history and the handwritings were quantitatively documented. Bradykinesia was determined by history and quantified by a finger tap, Purdue pegboard and a timed walk test. Similarly, hypophonia was determined by history and the volume of speech quantified using a decibel meter. Controls were enrolled for validation of handwriting test scores and decibel meter recordings.Primary outcome measuresPrevalence of micrographia in the PD cohort and the clinical factors that correlate with micrographia.Results68 subjects with PD were enrolled (68 men; mean age 72.3 years). Micrographia was identified in 63.2% of the cohort on verbal history and in 50% of the cohort when the handwriting test was used for ascertainment. Micrographia ascertained on history correlated significantly with disease severity (Hoehn & Yahr stage), motor impairment (Unified Parkinson's Disease Rating Scale), cognitive impairment (MMSE) and both bradykinesia and hypophonia determined by history and quantitative testing. Micrographia on handwriting test correlated with age (p=0.02), MMSE testing (p=0.04), hypophonia by history (p=0.01) and bradykinesia by quantitative testing (p=0.04).ConclusionMicrographia was found in nearly half of the PD cohort. Disease severity and impaired cognition were important clinical correlates. Micrographia had a significant relationship with bradykinesia and hypophonia, suggesting a possible overlap in their pathophysiology.
Adaptive capacity of the Adjusted Clinical Groups Case-Mix System to the cost of primary healthcare in Catalonia (Spain): a observational study
Authors: Sicras-Mainar Antoni , Velasco-Velasco Soledad , Navarro-Artieda Ruth , Prados-Torres Alexandra , Bolibar-Ribas Buenaventura , Violan-Fors Concepción ,   for the ACG Study Group
Published: June 2012

ObjectivesTo describe the adaptive capacity of the Adjusted Clinical Groups (ACG) system to the cost of care in primary healthcare centres in Catalonia (Spain).DesignRetrospective study (multicentres) conducted using computerised medical records.Setting13 primary care teams in 2008 were included.ParticipantsAll patients registered in the study centres who required care between 1 January and 31 December 2008 were finally studied. Patients not registered in the study centres during the study period were excluded.Outcome measuresDemographic (age and sex), dependent (cost of care) and case-mix variables were studied. The cost model for each patient was established by differentiating the fixed and variable costs. To evaluate the adaptive capacity of the ACG system, Pearson's coefficient of variation and the percentage of outliers were calculated. To evaluate the explanatory power of the ACG system, the authors used the coefficient of determination (R2).ResultsThe number of patients studied was 227 235 (frequency: 5.9 visits per person per year), with a mean of 4.5 (3.2) episodes and 8.1 (8.2) visits per patient per year. The mean total cost was €654.2. The explanatory power of the ACG system was 36.9% for costs (56.5% without outliers). 10 ACG categories accounted for 60.1% of all cases and 19 for 80.9%. 5 categories represented 71% of poor performance (N=78 887, 34.7%), particularly category 0300-Acute Minor, Age 6+ (N=26 909, 11.8%), which had a coefficient of variation =139% and 6.6% of outliers.ConclusionsThe ACG system is an appropriate manner of classifying patients in routine clinical practice in primary healthcare centres in Catalonia, although improvements to the adaptive capacity through disaggregation of some categories according to age groups and, especially, the number of acute episodes in paediatric patients would be necessary to reduce intra-group variation.
Barriers and facilitators to change in the organisation and delivery of endoscopy services in England and Wales: a focus group study
Authors: Rapport Frances , Seagrove Anne C , Hutchings Hayley A , Russell Ian T , Cheung Ivy , Williams John G , Cohen David 
Published: June 2012

ObjectiveExplore professional views of changes to gastroenterology service organisation and delivery and barriers and facilitators impacting on change. The work was undertaken as part of an evaluation in endoscopy service provision catalysed by the Modernising Endoscopy Services Programme of the Modernisation Agency.DesignFocus groups followed by analysis and group-working activities identifying key themes.SettingEnglish and Welshsecondary care gastroenterology units.Participants20 professionals working in gastroenterology in England and Wales. Medical, surgical and nursing specialists including endoscopy nurses. Opportunistic sampling to include senior people in leadership and management roles who were directly involved in service modernisation, excluding those involved in the Modernisation Endoscopy Services Programme.ResultsFour 1.5 h focus groups took place in 2007. Summative and thematic analyses captured essential aspects of text and achieved consensus on key themes. 4 themes were revealed: ‘loss of personal autonomy and erosion of professionalism’, ‘lack of senior management understanding’, ‘barriers and facilitators to change’ and ‘differences between English and Welsh units’. Themes indicated that low staff morale, lack of funding and senior management support were barriers to effective change. Limitations to the study include the disproportionately low number of focus group attendees from English units and the time delay in reporting these findings.ConclusionsDespite ambitions to implement change, ineffective management support continued to hamper modernisation of service organisation and delivery. While the National Health Service Modernisation Agency Modernising Endoscopy Services Programme acted as a catalyst for change, affecting the way staff work, communicate and think, it was not effective in heralding change itself. However, gastroenterologists were keen to consider the potential for change and future service modernisation. The methodological framework of innovative qualitative enquiry offers comprehensive and rigorous enhancement of quantitative studies, including randomised trials, when a mixed methods approach is needed.
Comparing the effectiveness of using generic and specific search terms in electronic databases to identify health outcomes for a systematic review: a prospective comparative study of literature search methods
Authors: Egan Matt , MacLean Alice , Sweeting Helen , Hunt Kate 
Published: June 2012

ObjectiveTo compare the effectiveness of systematic review literature searches that use either generic or specific terms for health outcomes.DesignProspective comparative study of two electronic literature search strategies. The ‘generic’ search included general terms for health such as ‘adolescent health’, ‘health status’, ‘morbidity’, etc. The ‘specific’ search focused on terms for a range of specific illnesses, such as ‘headache’, ‘epilepsy’, ‘diabetes mellitus’, etc.Data sourcesThe authors searched Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Education Resources Information Center for studies published in English between 1992 and April 2010.Main outcome measuresNumber and proportion of studies included in the systematic review that were identified from each search.ResultsThe two searches tended to identify different studies. Of 41 studies included in the final review, only three (7%) were identified by both search strategies, 21 (51%) were identified by the generic search only and 17 (41%) were identified by the specific search only. 5 of the 41 studies were also identified through manual searching methods. Studies identified by the two ELS differed in terms of reported health outcomes, while each ELS uniquely identified some of the review's higher quality studies.ConclusionsElectronic literature searches (ELS) are a vital stage in conducting systematic reviews and therefore have an important role in attempts to inform and improve policy and practice with the best available evidence. While the use of both generic and specific health terms is conventional for many reviewers and information scientists, there are also reviews that rely solely on either generic or specific terms. Based on the findings, reliance on only the generic or specific approach could increase the risk of systematic reviews missing important evidence and, consequently, misinforming decision makers. However, future research should test the generalisability of these findings.
Socioeconomic position and the risk of spontaneous abortion: a study within the Danish National Birth Cohort
Authors: Norsker Filippa Nyboe , Espenhain Laura , á Rogvi Sofie , Morgen Camilla Schmidt , Andersen Per Kragh , Nybo Andersen Anne-Marie 
Published: June 2012

ObjectivesTo investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion.DesignCohort study.Setting1996–2002, Denmark.ParticipantsAll first time participants, a total of 89 829 pregnant women, enrolled in the Danish National Birth Cohort were included in the present study. Overall, 4062 pregnancies ended in spontaneous abortion. Information on education, income and labour market attachment in the year before pregnancy was drawn from national registers.Main outcome measureSpontaneous abortion, that is, fetal death within the first 22 weeks of pregnancy, was the outcome of interest. The authors estimated HRs of spontaneous abortion using Cox regression analysis with gestational age as the underlying time scale.ResultsWomen with <10 years of education had an elevated risk of spontaneous abortion when compared with women with >12 years of education (HR 1.19 (95% CI 1.05 to 1.34)). The HR estimates for the four lowest income quintiles were all increased (HRs between 1.09 and 1.15) as compared with the upper quintile but did not differ considerably from each other. In general, no statistically significant association was found between labour market attachment and the risk of spontaneous abortion; however, the group of women on disability pension had an increased HR of spontaneous abortion when compared with women who were employed (HR 1.32 (95% CI 0.82 to 2.13)).ConclusionsEducational level and income were inversely associated with the risk of spontaneous abortion. As these factors most likely are non-causally related to spontaneous abortion, the findings indicate that factors related to social position, probably of the environmental and behavioural type, may affect spontaneous abortion risk. The study highlights the need for studies addressing such exposures in order to prevent spontaneous abortions.
Acupuncture for acute non-specific low back pain: a protocol for a randomised, controlled multicentre intervention study in general practice—the Acuback Study: Figure 1
Authors: Skonnord Trygve , Skjeie Holgeir , Brekke Mette , Grotle Margreth , Lund Iréne , Fetveit Arne 
Published: June 2012

IntroductionSome general practitioners (GPs) treat acute low back pain (LBP) with acupuncture, despite lacking evidence of its effectiveness for this condition. The aim of this study was to evaluate whether a single treatment session with acupuncture can reduce time to recovery when applied in addition to standard LBP treatment according to the Norwegian national guidelines. Analyses of prognostic factors for recovery and cost-effectiveness will also be carried out.Methods and analysisIn this randomised, controlled multicentre study in general practice in Southern Norway, 270 patients will be allocated into one of two treatment groups, using a web-based application based on block randomisation. Outcome assessor will be blinded for group allocation of the patients. The control group will receive standard treatment, while the intervention group will receive standard treatment plus acupuncture treatment. There will be different GPs treating the two groups, and both groups will just have one consultation. Adults who consult their GP because of acute LBP will be included. Patients with nerve root affection, ‘red flags’, pregnancy, previous sick leave more than 14 days and disability pension will be excluded. The primary outcome of the study is the median time to recovery (in days). The secondary outcomes are rated global improvement, back-specific functional status, sick leave, medication, GP visits and side effects. A pilot study will be conducted.Ethics and disseminationParticipation is based on informed written consent. The authors will apply for an ethical approval from the Regional Committee for Medical and Health Research Ethics when the study protocol is published. Results from this study, positive or negative, will be disseminated in scientific medical journals.Trial Registration NumberClinicalTrials.gov Identifier:NCT01439412.
Protocol for an observation and implementation study investigating optimisation of the management of stroke and transient ischaemic attack (TIA)
Authors: Sheppard James Peter , Mellor Ruth Mary , Bailey Sheila Marie , Barton Pelham , Boyal Amunpreet , Greenfield Sheila , Jowett Sue , Mant Jonathan , Quinn Tom , Singh Satinder , McManus Richard J ,   on behalf of the BBC CLAHRC Investigators
Published: June 2012

IntroductionPatients benefit from early and intensive treatment in both acute ischaemic stroke and transient ischaemic attack. Recent audits of acute stroke/transient ischaemic attack care suggest that although standards have improved, current services still fall short of optimal care. The aim of this study is to establish a database of patients accessing stroke services. Data will be collected and analysed to provide individualised feedback to healthcare professionals who can then use these findings to develop strategies for service improvement.Methods and analysisThis longitudinal observational study will evolve with the ongoing findings from the research output. The project will consist of three phases: assessment of current practice, feedback of findings and evaluation of service change. Consecutive patients will be recruited from participating hospitals, and identifiable data will be collected to link records from the Primary Care, Secondary Care and Emergency Services. As this study focuses on observation of current practice, a sample size calculation is not deemed appropriate. Patients will be sent follow-up questionnaires examining quality of life at 3 and 12 months post-event. Qualitative interviews will examine the care pathway through the experiences of patients, their carers, healthcare personnel and commissioners. Collected data will be used in economic analyses, which will evaluate the impact of current care and service redesign on the NHS costs and patient outcomes (death and quality of life).Ethics and disseminationEthical approval for this study has been obtained from the National Research Ethics Committee (reference; 09/H0716/71), and site-specific R&D approval has been acquired from the relevant NHS trusts. All findings will be presented at relevant healthcare/academic conferences and written up for publication in peer-reviewed journals. Results will be fed back to patients and participating trusts through a series of reports and presentations. These will be used to facilitate discussions about service redesign and implementation.
Network structure and the role of key players in a translational cancer research network: a study protocol
Authors: Long Janet C , Cunningham Frances C , Braithwaite Jeffrey 
Published: June 2012

IntroductionTranslational research networks are a deliberate strategy to bridge the gulf between biomedical research and clinical practice through interdisciplinary collaboration, supportive funding and infrastructure. The social network approach examines how the structure of the network and players who hold important positions within it constrain or enable function. This information can be used to guide network management and optimise its operations. The aim of this study was to describe the structure of a translational cancer research network (TCRN) in Australia over its first year, identify the key players within the network and explore these players' opportunities and constraints in maximising important network collaborations.Methods and analysisThis study deploys a mixed-method longitudinal design using social network analysis augmented by interviews and review of TCRN documents. The study will use network documents and interviews with governing body members to explore the broader context into which the network is embedded as well as the perceptions and expectations of members. Of particular interest are the attitudes and perceptions of clinicians compared with those of researchers. A co-authorship network will be constructed of TCRN members using journal and citation databases to assess the success of past pre-network collaborations. Two whole network social network surveys will be administered 12 months apart and parameters such as density, clustering, centrality and betweenness centrality computed and compared using UCINET and Netdraw. Key players will be identified and interviewed to understand the specific activities, barriers and enablers they face in that role.Ethics and disseminationEthics approvals were obtained from the University of New South Wales, South Eastern Sydney Northern Sector Local Health Network and Calvary Health Care Sydney. Results will be discussed with members of the TCRN, submitted to relevant journals and presented as oral presentations to clinicians, researchers and policymakers.
Combination Small Molecule MEK and PI3K Inhibition Enhances Uveal Melanoma Cell Death in a Mutant GNAQ- and GNA11-Dependent Manner
Authors: Khalili Jahan S. , Yu Xiaoxing , Wang Ji , Hayes Brendan C. , Davies Michael A. , Lizee Gregory , Esmaeli Bita , Woodman Scott E. 
Published: June 2012

Abstract
Purpose: Activating Q209L/P mutations in GNAQ or GNA11 (GNAQ/11) are present in approximately 80% of uveal melanomas. Mutant GNAQ/11 are not currently therapeutically targetable. Inhibiting key down-stream effectors of GNAQ/11 represents a rational therapeutic approach for uveal melanomas that harbor these mutations. The mitogen-activated protein/extracellular signal–regulated kinase/mitogen-activated protein kinase (MEK/MAPK) and PI3K/AKT pathways are activated in uveal melanoma. In this study, we test the effect of the clinically relevant small molecule inhibitors GSK1120212 (MEK inhibitor) and GSK2126458 (pan class I PI3K inhibitor) on uveal melanoma cells with different GNAQ/11 mutation backgrounds.
Experimental Design: We use the largest set of genetically annotated uveal melanoma cell lines to date to carry out in vitro cellular signaling, cell-cycle regulation, growth, and apoptosis analyses. RNA interference and small molecule MEK and/or PI3K inhibitor treatment were used to determine the dependency of uveal melanoma cells with different GNAQ/11 mutation backgrounds on MEK/MAPK and/or PI3K/AKT signaling. Proteomic network analysis was done to unveil signaling alterations in response to MEK and/or PI3K small molecule inhibition.
Results: GNAQ/11 mutation status was not a determinant of whether cells would undergo cell-cycle arrest or growth inhibition to MEK and/or phosphoinositide 3-kinase (PI3K) inhibition. A reverse correlation was observed between MAPK and AKT phosphorylation after MEK or PI3K inhibition, respectively. Neither MEK nor PI3K inhibition alone was sufficient to induce apoptosis in the majority of cell lines; however, the combination of MEK + PI3K inhibitor treatment resulted in the marked induction of apoptosis in a GNAQ/11 mutant–dependent manner.
Conclusions: MEK + PI3K inhibition may be an effective combination therapy in uveal melanoma, given the inherent reciprocal activation of these pathways within these cells. Clin Cancer Res; 18(16); 4345–55. ©2012 AACR.
The Zinc Finger Gene ZIC2 Has Features of an Oncogene and Its Overexpression Correlates Strongly with the Clinical Course of Epithelial Ovarian Cancer
Authors: Marchini Sergio , Poynor Elizabeth , Barakat Richard R. , Clivio Luca , Cinquini Michela , Fruscio Robert , Porcu Luca , Bussani Cecilia , D’Incalci Maurizio , Erba Eugenio , Romano Michela , Cattoretti Giorgio , Katsaros Dionyssios , Koff Andrew , Luzzatto Lucio 
Published: June 2012

Abstract
Purpose: Epithelial ovarian tumors (EOT) are among the most lethal of malignancies in women. We have previously identified ZIC2 as expressed at a higher level in samples of a malignant form (MAL) of EOT than in samples of a form with low malignant potential (LMP). We have now investigated the role of ZIC2 in driving tumor growth and its association with clinical outcomes.
Experimental Design: ZIC2 expression levels were analyzed in two independent tumor tissue collections of LMP and MAL. In vitro experiments aimed to test the role of ZIC2 as a transforming gene. Cox models were used to correlate ZIC2 expression with clinical endpoints.
Results: ZIC2 expression was about 40-fold in terms of mRNA and about 17-fold in terms of protein in MAL (n = 193) versus LMP (n = 39) tumors. ZIC2 mRNA levels were high in MAL cell lines but undetectable in LMP cell lines. Overexpression of ZIC2 was localized to the nucleus. ZIC2 overexpression increases the growth rate and foci formation of NIH3T3 cells and stimulates anchorage-independent colony formation; downregulation of ZIC2 decreases the growth rate of MAL cell lines. Zinc finger domains 1 and 2 are required for transforming activity. In stage I MAL, ZIC2 expression was significantly associated with overall survival in both univariate (P = 0.046) and multivariate model (P = 0.049).
Conclusions: ZIC2, a transcription factor related to the sonic hedgehog pathway, is a strong discriminant between MAL and LMP tumors: it may be a major determinant of outcome of EOTs. Clin Cancer Res; 18(16); 4313–24. ©2012 AACR.