Reference management software for systematic reviews and meta-analyses: an exploration of usage and usability

BACKGROUND: Reference management software programs enable researchers to more easily organize and manage large volumes of references typically identified during the production of systematic reviews. The purpose of this study was to determine the extent to which authors are using reference management software to produce systematic reviews; identify which programs are used most frequently and rate their ease of use; and assess the degree to which software usage is documented in published studies. METHODS: We reviewed the full text of systematic reviews published in core clinical journals indexed in ACP Journal Club from 2008 to November 2011 to determine the extent to which reference management software usage is reported in published reviews. We surveyed corresponding authors to verify and supplement information in published reports, and gather frequency and ease-of-use data on individual reference management programs. RESULTS: Of the 78 researchers who responded to our survey, 79.5% reported that they had used a reference management software package to prepare their review. Of these, 4.8% reported this usage in their published studies. EndNote, Reference Manager, and RefWorks were the programs of choice for more than 98% of authors who used this software. Comments with respect to ease-of-use issues focused on the integration of this software with other programs and computer interfaces, and the sharing of reference databases among researchers. CONCLUSIONS: Despite underreporting of use, reference management software is frequently adopted by authors of systematic reviews. The transparency, reproducibility and quality of systematic reviews may be enhanced through increased reporting of reference management software usage

Absence of bias against smokers in access to coronary revascularization after cardiac catheterization

Objective. Many consider smoking to be a personal choice for which individuals should be held accountable. We assessed whether there is any evidence of bias against smokers in cardiac care decision-making by determining whether smokers were as likely as non-smokers to undergo revascularization procedures after cardiac catheterization. Design. Prospective cohort study. Subjects and setting. All patients undergoing cardiac catheterization in Alberta, Canada. Main measures. Patients were categorized as current smokers, former smokers, or never smokers, and then compared for their risk-adjusted likelihood of undergoing revascularization procedures (percutaneous coronary intervention or coronary artery bypass grafting) after cardiac catheterization. Results. Among 20406 patients undergoing catheterization, 25.4% were current smokers at the time of catheterization, 36.6% were former smokers, and 38.0% had never smoked. When compared with never smokers (reference group), the hazard ratio for undergoing any revascularization procedure after catheterization was 0.98 (95% CI 0.93-1.03) for current smokers and 0.98 (0.94-1.03) for former smokers. The hazard ratio for undergoing coronary artery bypass grafting was 1.09 (1.00-1.19) for current smokers and 1.00 (0.93-1.08) for former smokers. For percutaneous coronary intervention, the hazard ratios were 0.93 (0.87-0.99) for current smokers and 1.00 (0.94-1.06) for former smokers. Conclusion. Despite potential for discrimination on the basis of smoking status, current and former smokers undergoing cardiac catheterization in Alberta, Canada were as likely to undergo revascularization procedures as catheterization patients who had never smoke

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

International variation in the definition of ‘main condition' in ICD-coded health data

Hospital-based medical records are abstracted to create International Classification of Disease (ICD) coded discharge health data in many countries. The ‘main condition' is not defined in a consistent manner internationally. Some countries employ a ‘reason for admission' rule as the basis for the main condition, while other countries employ a ‘resource use' rule. A few countries have recently transitioned from one of these approaches to the other. The definition of ‘main condition' in such ICD data matters when it is used to define a disease cohort to assign diagnosis-related groups and to perform risk adjustment. We propose a method of harmonizing the international definition to enable researchers and international organizations using ICD-coded health data to aggregate or compare hospital care and outcomes across countries in a consistent manner. Inter-observer reliability of alternative harmonization approaches should be evaluated before finalizing the definition and adopting it worldwid

Loss of protein kinase calpha expression may enhance the tumorigenic potential of Gli1 in basal cell carcinoma

Gli1 has now been implicated in switching between motility and static cell replication. Part of a series of papers, this study tracted PKCalpha expression in relation to Gli1 in various static and motile cell areas of the hair sheath and BCC

Exploiting the efficacy of Tyro3 and folate receptors to enhance the delivery of gold nanoparticles into colorectal cancer cells in vitro

Colorectal cancer (CRC) is the fourth most common cancer in the world. Due to its asymptomatic nature, CRC is diagnosed at an advanced stage where the survival rate is <5%. Besides, CRC treatment using chemotherapy, radiotherapy and surgery often causes undesirable side-effects. As such, gold nanoparticles (GNPs) are envisaged in the field for the diagnosis and treatment of CRC. GNPs have unique physical, chemical and electrical properties at the nanoscale which make them suitable for application in biomedicine. However, for GNPs to become clinically effective, their internalisation efficiency in cancer cells must be enhanced. Folate receptor-α (FR) is overexpressed in CRC cells wherein FR helps in the uptake of folic acid within the cells. Tyro3, a novel tyrosine kinase receptor, drives cell proliferation and its overexpression is correlated with poor prognosis in CRC. Their upregulated expression in CRC cells relative to normal cells makes them an ideal target for GNPs using active targeting. Therefore, in this study receptors FR and Tyro3 were simultaneously targeted using specific antibody-coated GNPs in order to enhance the uptake and internalisation of GNPs in CRC cells in vitro. Four different types of coated-GNPs were synthesised GNPs-PEG, GNPs-anti-FR, GNPs-anti-Tyro3 and GNPs-anti-(FR + Tyro3) and incubated (0–50 ng) with three CRC cell lines namely CRL1790, CRL2159 and HCT116. Simultaneous targeting of these receptors by GNPs-anti-(FR + Tyro3) was found to be the most effective in internalisation in CRC cells compared with GNPs targeted singly to FR or Tyro3 (p <0.05). Besides this, results show that Tyro3 mediated similar internalisation efficacy to FR (p <0.05) in CRC cells using ICP-OES

The role of ectopic human chorionic gonadotropin beta subunit in inducing epithelial mesenchymal transition in human keratinocytes and its possible pathways

Background: The process of epithelial-mesenchymal transition (EMT) involves the trans-differentiation of epithelial cells to mesenchymal cells associated with high plasticity. It usually occurs when the cells acquire migratory and invasive characteristics due to the weakening or the loss of cell-cell adhesion. Human chorionic gonadotropin (hCG), a pregnancy hormone, consists of a common α subunit which is shared by three other hormones, thyroid stimulating hormone, luteinizing hormone and follicular stimulating hormone; and an unique β subunit (hCGβ). Previous studies have demonstrated that hCGβ was expressed by some epithelial origin cancers (1, 2, 3) and therefore it has been postulated as a possible epithelial cancer biomarker. Other studies have linked the presence hCGβ to the aggressive and invasive behavior of certain cancers and their poor prognosis (3, 4). Methods: This study was set out to investigate whether hCGβ plays a role in inducing the EMT and to elucidate the possible pathways. Human keratinocytes (HK) were exposed to spent media collected from hCGβ producing cancer cells (ScaBER cells) for 48 hours before the cells were either fixed for immnuostaining or cells were lysed and protein extracts were collected for western blotting analysis. The expression of epithelial and mesenchymal markers was evaluated by both florescent immunocytochemistry and western blotting techniques. Results: A trend of up-regulation of mesenchymal markers (Vimentin and β-catenin) and down regulation of epithelial marker (E-cadherin) in these treated HK cells was observed. There was 50% increase in cell number which was positively stained by anti-Vimentin antibody whilst 16% of the cells have lost E-cadherin expression (100% to 84%) following 48 hours’ exposure to the hCGβ containing media. These findings were in consistence with the results from HK cells that were exposed to recombinant hCGβ (r-hCGβ). It was also observed that the changes in the expressions of these markers were reduced when a combination of three anti-hCGβ antibodies targeting different hCGβ epitopes was added to the spent media. These results were confirmed by western blotting analysis. Conclusion: The findings suggest that ectopic hCGβ produced by cancer cells might be involved in EMT associated with the migratory and aggressive behavior of such cancers. Furthermore, the up-regulation of β-catenin also suggests its possible role in the Wnt pathway which offers an insight into EMT process at a molecular level. This could be valuable point in developing future novel anti hCGβ therapies for such types of cancers

Effective delivery of arsenic trioxide to HPV-positive cervical cancer cells using optimised liposomes: a size and charge study

Despite the success of arsenic trioxide (ATO) in treating haematological malignancies, its potential to treat solid tumours has not been fully exploited, owing to its dose-limiting toxicity and poor pharmacokinetics. In order to overcome this hurdle, liposomal encapsulation of the drug with different surface charges (neutral, negative, and positive) and sizes (100, 200 and 400 nm) were synthesised and tested on human papilloma virus (HPV)-positive HeLa and HPV-negative HT-3 cervical cancer cell lines. Two epithelial cell lines-human keratinocytes (HK) and human colon cells (CRL-1790)-were used as controls. The synthesised liposomes were tested for their physico-chemical characteristics, drug loading efficiency, and toxicity on the studied cell lines. Neutral liposomes of 100 nm in size were the chosen formulation for delivering ATO into the studied cells, as they showed the least intrinsic cytotoxicity and the highest loading efficiency. The findings demonstrated that the optimised formulation of liposomes was an effective drug delivery method for HPV-infected cervical cancer cells. Furthermore, the toxicity vs. uptake ratio was highest for HeLa cells, while a reduced or minimal toxic effect was observed for non-HPV-infected cervical cancer cells and control cells. These findings may provide a promising therapeutic strategy for effectively managing cervical cancers

Modelling and validating three dimensional human normal cervix and cervical cancer tissues in vitro

Objective: The use of three dimensional in vitro systems in cancer research is a promising path for developing effective anticancer therapies. The aim of this study was to engineer a functional 3-D in vitro model of normal and cancerous cervical tissue. Methods: Normal epithelial and immortalized cervical epithelial carcinoma cell lines were used to construct 3-D artificial normal cervical and cervical cancerous tissues. De-epidermised dermis (DED) was used as a scaffold for both models. Morphological analyses were conducted by using haematoxylin and eosin staining and characteristics of the models were studied by analysing the expression of different structural cytokeratins and differential protein marker Mad1 using immunohistochemical technique. Results: Haematoxylin and eosin staining results showed that normal cervical tissue had multi epithelial layers while cancerous cervical tissue showed dysplastic changes. Immunohistochemistry staining results revealed that for normal cervix model cytokeratin 10 was expressed in the upper stratified layer of epithelium while cytokeratin 5 was expressed mainly in the middle and basal layer. Cytokeratin 19 was weakly expressed in a few basal cells. Cervical cancer model showed cytokeratin 19 expression in different epithelial layers and weak or no expression for cytokeratin 5 and cytokeratin 10. Mad1 expression was detected in some suprabasal cells. Conclusions: The 3-D in vitro models showed stratified epithelial layers and expressed the same types and patterns of differentiation marker proteins as seen in corresponding in vivo tissue in either normal cervical or cervical cancerous tissue. Findings imply that they can serve as functional normal and cervical cancer models