cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5127106
title: Supplementary Material for: Temporal Trends in Polypharmacy and Hyperpolypharmacy in Older New Zealanders over a 9-Year Period: 2005-2013

description: <b><i>Background:</i></b> Polypharmacy and hyperpolypharmacy are proxy indicators for inappropriate medicine use. Inappropriate medicine use in older people leads to adverse clinical outcomes. <b><i>Objective:</i></b> The objectives of this study were to investigate the prevalence and trends of polypharmacy and hyperpolypharmacy in older people in New Zealand from 2005 to 2013, analyzing the pharmaceutical collections maintained by the Ministry of Health. <b><i>Methods:</i></b> A repeated cross-sectional analysis of population-level dispensing data was conducted from January 1, 2005 to December 31, 2013. Polypharmacy and hyperpolypharmacy in individuals were defined as the use of 5-9 medicines and ≥10 medicines, respectively, dispensed concurrently for a period of ≥90 days. Differences in polypharmacy and hyperpolypharmacy between 2005 and 2013 were examined. A multinomial regression model was used to predict sociodemographic characteristics associated with polypharmacy and hyperpolypharmacy. <b><i>Results:</i></b> Polypharmacy and hyperpolypharmacy were found to be higher in 2013 compared to 2005 (polypharmacy: 29.5 vs. 23.4%, p &lt; 0.001; hyperpolypharmacy: 2.1 vs. 1.3%, p &lt; 0.001). The risk of polypharmacy and hyperpolypharmacy was higher in females, in those aged 80-84 years, in the Māori population (for polypharmacy) and the Middle Eastern, Latin American, or African population (for hyperpolypharmacy), in people living in the Southern-district health board, and in individuals with increasing deprivation. <b><i>Conclusion:</i></b> The population of New Zealand is aging and the number of older people with multiple chronic conditions is increasing. The proportion of older people exposed to polypharmacy and hyperpolypharmacy has increased in 2013 compared to 2005. Our study provides important information to alert health policy makers, researchers, and clinicians about the dire need to reduce the medication burden in older New Zealanders.
DOI: 10.6084/m9.figshare.5127112
title: Supplementary Material for: p16 Gene Transfer Induces Centrosome Amplification and Abnormal Nucleation Associated with Survivin Downregulation in Glioma Cells

description: <b><i>Objective:</i></b> In human glioma cells, p16 gene transfer induced G1/S arrest, increased radiosensitivity and abnormal nucleation (especially bi- and multinucleation). Survivin suppression caused G2/M arrest, radiosensitization and an increase in aneuploidy accompanied by centrosome amplification. Abnormal nucleation and aneuploidy represent chromosome instability (CIN), and it is well known that centrosome amplification leads to CIN. However, little has been reported that suggests that transferring p16 causes centrosome overduplication during the G1/S phase. <b><i>Methods:</i></b> The p16 gene was transferred into p16-null human glioma cell lines (U251MG and D54MG) using adenovirus with or without irradiation. Centrosome amplification was evaluated by immunofluorescence. We also investigated the DNA replication licensing factor CDT1, its inhibitor geminin and survivin expression as regulators of chromosomal segregation. <b><i>Results:</i></b> p16 gene transfer with radiation initiated the greatest degree of centrosome overduplication. CDT1 showed low levels, geminin was unchanged and survivin decreased in Ax-hp16-infected cells with radiation. Those changes of factors affecting DNA licensing or chromosomal segregation might contribute to CIN. <b><i>Conclusion:</i></b> p16 transfer caused centrosome amplification even in G1/S phase-arrested cells. This suggests that p16 is involved in abnormal nucleation and radiosensitization in human glioma cells.
DOI: 10.6084/m9.figshare.5127103
title: Supplementary Material for: Patients' Perceptions of Research Biopsies in Phase I Oncology Trials

description: <b><i>Objective:</i></b> Research biopsies are increasingly incorporated into phase I oncology trials resulting in ethical and logistical challenges for patients and clinicians. Patients' understanding and willingness to undergo these biopsies are crucial. <b><i>Methods:</i></b> Over 12 months, we administered a questionnaire comprising three sections: demographics and previous cancer therapy, understanding of phase I trials and personalized medicine, and understanding of biopsies and associated risks. <b><i>Results:</i></b> Out of 56 patients approached, 47 patients completed the questionnaire. Overall, the patients were well informed about the concepts of personalized medicine and 89% (n = 42) were aware that early phase clinical trials aim to define a dose and explore side effects of new drugs. Interestingly, 76% (n = 36) expected early phase trials to improve symptoms, quality of life and survival. Offering hope and feeling in control of their treatment were important components for 80% (n = 38) and 57% (n = 27), respectively. The majority of this highly selective patient cohort understood the concept of research biopsies, with 59% (n = 28) willing to have a fresh research biopsy for trial participation. Although 72% (n = 34) felt that research biopsies should be optional, only 19% (n = 9) would not participate in a clinical trial with mandatory biopsies. Compared to diagnostic biopsies, the patients were less likely to accept associated risks with research biopsies. <b><i>Conclusion:</i></b> As research biopsies are crucial to many components of the drug development process, our study provides evidence for patients' overall willingness to undergo research biopsies for trial purposes. A consent process tailored to the biopsy site may help patients weigh up the associated risks versus benefits. © 2014 S. Karger AG, Basel
DOI: 10.6084/m9.figshare.5127109
title: Supplementary Material for: A Novel <b><i>ERCC6</i></b> Splicing Variant Associated with a Mild Cockayne Syndrome Phenotype

description: <b><i>Background:</i></b> Cockayne syndrome is an autosomal recessive, heterogeneous syndrome with classical features, including short stature, microcephaly, developmental delay, neuropathy, and photosensitivity. New genomic approaches offer improved molecular diagnostic potential. <b><i>Methods:</i></b> Whole-exome sequencing was employed to study a consanguineous extended family with severe short stature and variable presentations of peripheral neuropathy, lipoatrophy, photosensitivity, webbed neck, and hirsutism. <b><i>Results:</i></b> We identified a novel homozygous <i>ERCC6</i> variant at the donor splice site of intron 9 <i>(c.1992 + 3A&gt;G)</i>, which was predicted to only slightly perturb splicing efficiencies. Assessment of primary fibroblast-derived mRNAs, however, revealed a dominant splicing species that utilized an unsuspected putative donor splice site within exon 9, resulting in predicted early protein termination (p.Arg637Serfs*34). <b><i>Conclusions:</i></b> We describe a new splicing <i>ERCC6</i> defect causal of Cockayne syndrome. The application of exome sequence analysis was integral to diagnosis, given the complexity of phenotypic presentation in the affected family members. The novel splicing defect, furthermore, illustrates how a seemingly minor change in the relative strength of a splice site can have significant biological consequences.
DOI: 10.6084/m9.figshare.5127121.v1
title: Supplementary Material for: Genetic Variants Are Not Associated with Outcome in Patients with Coronary Artery Disease and Left Ventricular Dysfunction: Results of the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) Trials

description: <b><i>Objectives and Background:</i></b> We evaluated the ability of 23 genetic variants to provide prognostic information in patients enrolled in the Genetic Substudy of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. <b><i>Methods:</i></b> Patients assigned to STICH Hypothesis 1 were randomized to medical therapy with or without coronary artery bypass grafting (CABG). Those assigned to STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. <b><i>Results:</i></b> In patients assigned to STICH Hypothesis 2 (n = 714), no genetic variant met the prespecified Bonferroni-adjusted threshold for statistical significance (p &lt; 0.002); however, several variants met nominal prognostic significance: variants in the β<sub>2</sub>-adrenergic receptor gene (β<sub>2</sub>-AR Gln27Glu) and in the A<sub>1</sub>-adenosine receptor gene (A<sub>1</sub>-717 T/G) were associated with an increased risk of a subject dying or being hospitalized for a cardiac problem (p = 0.027 and 0.031, respectively). These relationships remained nominally significant even after multivariable adjustment for prognostic clinical variables. However, none of the 23 genetic variants influenced all-cause mortality or the combination of death or cardiovascular hospitalization in the STICH Hypothesis 1 population (n = 532) by either univariate or multivariable analysis. <b><i>Conclusion:</i></b> We were unable to identify the predictive genotypes in optimally treated patients in these two ischemic heart failure populations.
DOI: 10.6084/m9.figshare.5127097
title: Supplementary Material for: Treatment Outcome and Relevance of Palliative Chemotherapy in Urachal Cancer

description: <b><i>Background:</i></b> Urachal cancer is a rare malignancy that accounts for &lt;1% of bladder cancers. There is currently no consensus on the diagnosis and management of urachal cancer and there are very few reports on palliative chemotherapy for unresectable disease. We delineate the clinical features and treatment outcome of urachal cancer, in particular the relevance of palliative chemotherapy in recurrent, metastatic disease. <b><i>Methods:</i></b> The clinicopathologic variables and treatment outcome of patients who were treated for urachal cancer were retrospectively reviewed. <b><i>Results:</i></b> Among 28 eligible patients, 25 had localized disease and 3 had metastatic disease at initial diagnosis. All patients with localized disease underwent curative resection and there was disease recurrence in 10. Out of 13 patients with metastatic disease either at initial diagnosis or during follow-up, the lung was the most common metastatic site (n<i> = </i>5), followed by the liver, bone and peritoneum. Ten patients received palliative chemotherapy. A total of 24 chemotherapeutic regimens were administered; regimens with a base of fluoropyrimidine (5-FU), taxane and gemcitabine were the most common. The overall response rate of all chemotherapeutic regimens was 16.7%. The 5-FU-based regimens showed a good response, with 2 of 4 patients who received these showing a partial response. One tumor with a partial small-cell component showed a partial response to both an etoposide-based regimen and a taxane-based regimen. <b><i>Conclusions:</i></b> In urachal cancer, curative surgery is still the recommended treatment with respect to overall survival. A 5-FU-based chemotherapy regimen could be considered for metastatic recurrent disease. © 2014 S. Karger AG, Basel
DOI: 10.6084/m9.figshare.5127100
title: Supplementary Material for: Cost-Effectiveness of Endobronchial Valve Therapy for Severe Emphysema: A Model-Based Projection Based on the VENT Study

description: <b><i>Background:</i></b> Endobronchial valve (EBV) therapy is an innovative treatment that has been shown to be safe and effective in selected subgroups of patients with severe emphysema. <b><i>Objectives:</i></b> The objective of our study was to assess the cost-effectiveness of EBV therapy compared to the medical management of patients with high heterogeneity, complete fissures and lobar exclusion in the context of the German health-care system. <b><i>Methods:</i></b> Clinical data from a subset of VENT (Endobronchial Valve for Emphysema Palliation Trial) provided information about clinical events, health-related quality of life, and disease staging for 12 months. This information was subsequently used to project long-term disease progression, mortality, and health resource utilization. We computed the 5- and 10-year incremental cost-effectiveness ratio (ICER) in euros per quality-adjusted life year (QALY). Costs and effects were discounted at 3% per year. <b><i>Results:</i></b> EBV therapy led to clinically meaningful disease restaging at 12 months (37.8% of the cohort improved staging, compared to 0% in the controls). Over 5 years, EBV therapy was projected to increase survival from 66.4 to 70.7%, and to add 0.22 QALYs. Costs were estimated to increase by EUR 10,299, resulting in an ICER of EUR 46,322 per QALY. Over 10 years, 0.41 QALYs were gained at an additional cost of EUR 10,425, yielding an ICER of EUR 25,142 per QALY. <b><i>Conclusions:</i></b> Our model-based analysis suggests that EBV therapy leads to clinically meaningful changes in disease staging and progression when compared to medical management, with resulting gains in unadjusted and quality-adjusted life expectancy. Our results indicate that EBV therapy is cost-effective in the German health-care system.
DOI: 10.6084/m9.figshare.5127106.v1
title: Supplementary Material for: Temporal Trends in Polypharmacy and Hyperpolypharmacy in Older New Zealanders over a 9-Year Period: 2005-2013

description: <b><i>Background:</i></b> Polypharmacy and hyperpolypharmacy are proxy indicators for inappropriate medicine use. Inappropriate medicine use in older people leads to adverse clinical outcomes. <b><i>Objective:</i></b> The objectives of this study were to investigate the prevalence and trends of polypharmacy and hyperpolypharmacy in older people in New Zealand from 2005 to 2013, analyzing the pharmaceutical collections maintained by the Ministry of Health. <b><i>Methods:</i></b> A repeated cross-sectional analysis of population-level dispensing data was conducted from January 1, 2005 to December 31, 2013. Polypharmacy and hyperpolypharmacy in individuals were defined as the use of 5-9 medicines and ≥10 medicines, respectively, dispensed concurrently for a period of ≥90 days. Differences in polypharmacy and hyperpolypharmacy between 2005 and 2013 were examined. A multinomial regression model was used to predict sociodemographic characteristics associated with polypharmacy and hyperpolypharmacy. <b><i>Results:</i></b> Polypharmacy and hyperpolypharmacy were found to be higher in 2013 compared to 2005 (polypharmacy: 29.5 vs. 23.4%, p &lt; 0.001; hyperpolypharmacy: 2.1 vs. 1.3%, p &lt; 0.001). The risk of polypharmacy and hyperpolypharmacy was higher in females, in those aged 80-84 years, in the Māori population (for polypharmacy) and the Middle Eastern, Latin American, or African population (for hyperpolypharmacy), in people living in the Southern-district health board, and in individuals with increasing deprivation. <b><i>Conclusion:</i></b> The population of New Zealand is aging and the number of older people with multiple chronic conditions is increasing. The proportion of older people exposed to polypharmacy and hyperpolypharmacy has increased in 2013 compared to 2005. Our study provides important information to alert health policy makers, researchers, and clinicians about the dire need to reduce the medication burden in older New Zealanders.
DOI: 10.6084/m9.figshare.5127094
title: Supplementary Material for: Decreased Blood Flow after Sorafenib Administration Is an Imaging Biomarker to Predict Overall Survival in Patients with Advanced Hepatocellular Carcinoma

description: <b><i>Background:</i></b> Sorafenib is a multikinase inhibitor targeting Raf and protein tyrosine kinases, which are involved in cell growth and tumor angiogenesis. Sorafenib administration induces temporary inhibition of tumor growth and a decrease in arterial blood flow in a considerable number of hepatocellular carcinoma (HCC) patients. We retrospectively evaluated the association between decreased blood flow and the overall survival (OS) of HCC patients after the initiation of sorafenib therapy. <b><i>Patients and Methods:</i></b> Therapeutic responses of 158 advanced HCC patients with hypervascular tumors who had received sorafenib for more than 1 month were analyzed. To assess their therapeutic response, patients underwent radiological evaluation before and every 4-6 weeks after the initiation of sorafenib treatment. After the classification of patients into three groups based on the change in arterial enhancement during treatment (no change, decrease and disappearance), the OS of each group was compared using the Kaplan-Meier method. <b><i>Results:</i></b> Statistically significant differences in OS were observed among the three groups (p &lt; 0.001). A decrease or disappearance of arterial enhancement was significantly associated with improved OS compared to patients with no change in arterial enhancement; the median OS was 19.9 months (95% confidence interval, CI, 16.4-24.5 months) and 6.0 months (95% CI, 4.0-8.8 months), respectively (p &lt; 0.001). However, there was no difference in OS between the decrease and disappearance groups (p = 0.88). <b><i>Conclusion:</i></b> We conclude that decreased arterial enhancement during sorafenib treatment was associated with the longest OS and could therefore reflect an effective response.
DOI: 10.6084/m9.figshare.5127085
title: Supplementary Material for: <b><i>UCH-L1</i></b> S18Y Variant and Risk of Parkinson's Disease in Asian Populations: An Updated Meta-Analysis

description: The ubiquitin carboxy-terminal hydrolase L1 <i>(UCH-L1)</i> gene has been implicated in the etiology of Parkinson's disease (PD). Several studies have evaluated the association between the<i> UCH-L1 </i>S18Y variant and the risk of PD. However, conflicting results have been reported. Therefore, we performed a meta-analysis to explore whether the <i>UCH-L1</i> S18Y variant is associated with susceptibility to PD in Asians. A database search in Web of Science, MEDLINE, Embase and PubMed up to March 2014 identified 10 studies comprising 4,897 PD patients and 4,446 controls in total, which were included in this meta-analysis. In an updated meta-analysis, no significant associations between the S18Y polymorphism and PD in Asians were observed in recessive [p = 0.28, odds ratio (OR) = 1.47, 95% confidence interval (CI): 0.86-1.04] or dominant models (p = 0.46, OR = 0.96, 95% CI: 0.88-1.06). In the subgroup analysis by ethnicity, still no significant association was detected in dominant (for Chinese, OR = 0.97, 95% CI: 0.85-1.10; for Japanese, OR = 0.96, 95% CI: 0.83-1.11) and recessive models (for Chinese, OR = 0.99, 95% CI: 0.88-1.11; for Japanese, OR = 0.89, 95% CI: 0.76-1.04). The results of this meta-analysis suggested that the <i>UCHL-1 </i>S18Y polymorphism was not associated with the risk of PD in Asians. To our knowledge, this is the latest and largest meta-analysis assessing the association of the<i> UCHL-1 </i>S18Y variant with the risk of PD in Asian ancestry.
DOI: 10.6084/m9.figshare.5127088
title: Supplementary Material for: The Study of Breast Milk IGF-1, Leptin, Ghrelin and Adiponectin Levels as Possible Reasons of High Weight Gain in Breast-Fed Infants

description: <b><i>Background:</i></b> Excessive consumption of protein that leads to increased blood levels of insulin-like growth factor-1 (IGF-1) is an important risk factor for high growth velocity and obesity in formula-fed infants. However, it is not clear whether these factors can explain the high growth velocity in breast-fed infants. <b><i>Aim:</i></b> To study the possible links between the growth velocity in breast-fed infants and the levels of protein, IGF-1 and other hormones, which regulate energy homeostasis, in mothers' breast milk. <b><i>Methods:</i></b> We studied 103 mother-infant pairs. Their daily breast milk intake and level of IGF-1, leptin, ghrelin, adiponectin, protein and fat in breast milk were measured at 1, 2 and 3 months of lactation. The infant group was divided into three subgroups of low, normal and high weight gain tertiles. <b><i>Results:</i></b> The breast milk consumed by the infants with high weight gain contained higher levels of IGF-1 than that consumed by those with low weight gain at all periods studied (p = 0.032 at 3 months of lactation), and ghrelin levels were higher at 1 and 2 months and leptin levels at 2 and 3 months of lactation (p &lt; 0.05). A positive correlation was observed between the breast milk IGF-1 level and infant weight gain (r = 0.294, p = 0.043). Total daily breast milk, fat and hormone intake was also higher in the high weight gain group compared to the low weight gain group. <b><i>Conclusion:</i></b> One of the reasons for the high growth velocity in breast-fed infants may be the enhanced levels of the studied hormones in breast milk.
DOI: 10.6084/m9.figshare.5127091
title: Supplementary Material for: Duration of Stable Disease Is Associated with Overall Survival in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

description: <b><i>Background:</i></b> Sorafenib is a molecular-targeting agent showing improved overall survival (OS) for advanced hepatocellular carcinoma (HCC). Although tumor dormancy, characterized by stable tumor status or stable disease (SD) without tumor regression, is a unique feature of sorafenib treatment, the contribution of SD to OS remains debatable. This study aimed to clarify the correlation between SD periods and OS in patients with HCC treated with sorafenib. <b><i>Methods:</i></b> From May 2009 to January 2013, 269 patients with advanced-stage HCC were treated with sorafenib at the Kinki University Hospital. The antitumor response of sorafenib was evaluated in 158 patients using the modified Response Evaluation Criteria in Solid Tumors, and patients with SD were divided into two subgroups according to the median duration of SD: short SD (&lt;3 months) and long SD (≥3 months). The relationship between the duration of SD and OS was analyzed among patients with complete (CR) and partial response (PR), and long and short SD using the Kaplan-Meier method. <b><i>Results:</i></b> The median OS was 5.7 months in the short SD, 20.8 months in the long SD and 17.9 months in the CR + PR group. Although the duration of OS was significantly longer in the long SD group than the short SD group, no difference in OS was detected between the patients with CR + PR and patients with long SD. The impact of long SD on OS could be as strong as that of CR + PR. <b><i>Conclusion:</i></b> Achievement of long SD is one of the important goals for improving survival in patients with HCC treated with sorafenib.
DOI: 10.6084/m9.figshare.5127082
title: Supplementary Material for: Patient Knowledge of Antithyroid Drug-Induced Agranulocytosis

description: <b><i>Background:</i></b> Agranulocytosis is a serious side effect of antithyroid drugs. <b><i>Objective:</i></b> To ascertain the knowledge of patients and review the quality of information available on the internet. <b><i>Methods:</i></b> A questionnaire survey was performed for patients receiving antithyroid drugs. Patients attending endocrine clinics who were receiving antithyroid drug treatment (group A, n = 33) were interviewed. A further national cohort of patients (group B, n = 100) treated with antithyroid drugs, participated in an online survey. <b><i>Results:</i></b> 60.9% of responders were not aware of the common symptoms of agranulocytosis. 18.6% had never received any information about side effects. Of the 108 patients who recalled receiving information, 30% rated the quality as ‘poor' or ‘not good at all'. Structured interviews of group A patients revealed that almost half (45.5%, 15/33) had experienced symptoms that could be indicative of agranulocytosis, but only 53.3% (8/15) had a blood count checked. A review of 20 selected patient information internet sites revealed a significant variation in advice given to patients. <b><i>Conclusions:</i></b> Inadequate knowledge about agranulocytosis among patients receiving antithyroid drug treatment is common. The available information on the internet is variable and inconsistent.