Can you believe what you read in the papers?

The number of reports of clinical trials grows by hundreds every week. However, this does not mean that people making decisions about healthcare are finding it easier to obtain reliable knowledge for these decisions. Some of the information is unreliable. Systematic reviews are helping to resolve this by bringing together the research on a topic, appraising and summarising it. But the quality of these reviews depends greatly on the quality of the studies, and this usually means the quality of their reports. If there are fundamental flaws within a study, such as the use of inappropriate 'randomisation' techniques in the context of reviews of the effects of interventions, the reviewers will not be able to fix these. Worse still, if they are not aware of underlying flaws, they might make incorrect judgements about the quality of the research in their review. A study by Wu and colleagues of 'randomised trials' from China provides a reminder of the cautious approach needed by users of scientific articles. They contacted the authors of more than 2000 research articles, which purported to be reports of randomised trials; and concluded that ten of every 11 studies claiming to be a randomised trial probably did not use random allocation. Better education of researchers, peer reviewers and editors about what is, and is not, a properly randomised trial is needed; along with better reporting of the details for how participants were allocated to the different interventions. Systematic reviewers must be cautious in making assumptions about the conduct of trials based on simple phrases about the trial methodology, rather than a full description of the methods actually used. It's not that you can't believe anything that you read in the papers, just that you cannot believe everything

Multi-objective optimization of CCHP system with hybrid chiller under new electric load following operation strategy

The performance of combined cooling, heating and power (CCHP) system is greatly affected by its operating strategy and design. In this paper, a new electric load following (NELF) strategy was developed. It is based on the alternation between absorption cooling and electric cooling according to the building energy requirements, for hybrid chiller based CCHP systems. A comparison of the new proposed strategy with the modified electric load following (MELF) and electric load following (ELF) strategies is performed. A multi-objective optimization approach based on genetic algorithm is carried out to predict the optimal capacity of CCHP systems. Performance criteria like primary energy consumption, annual total cost and carbon dioxide emission were considered as objective functions. The performances of these CCHP systems and operation strategies were examined and compared with the separated production (SP) system for a Mosque complex located in Algiers, Algeria. Results show that hybrid chiller CCHP based NELF strategy is the best choice, which can reduce the primary energy consumption by 34.45 GWh/year, annual total cost by 0.313 million €/year and carbon dioxide emission by 8.37 kton/year. Compared to the other configurations and strategies, the hybrid CCHP based NELF achieves better energetic, economic and environmental performance under the optimized conditions

Water-borne Polymeric Nanoparticles for Glutathione-Mediated Intracellular Delivery of Anticancer Drugs.

A new family of water-borne, biocompatible and carboxyl- functionalized nanogels was developed for glutathione- mediated delivery of anticancer drugs. Poly(N-vinyl- pyrrolidone)-co-acrylic acid nanogels were generated by e- beam irradiation of aqueous solutions of a crosslinkable polymer, using industrial-type linear accelerators and set- ups. Nanogels physico-chemical properties and colloidal stability, in a wide pH range, were investigated. In vitro cell studies proved that the nanogels are fully biocompatible and able to quantitatively bypass cellular membrane. An anticancer drug, doxorubicin (DOX), was linked to the carboxyl groups of NGs through a spacer containing a disulphide cleavable linkage. In vitro release studies showed that glutathione is able to trigger the release of DOX through the reduction of the S-S linkage at a concentration comparable to its levels in the cytosol

Functionalized poly(N-isopropylacrylamide)-based microgels in tumor targeting and drug delivery

Over the past several decades, the development of engineered small particles as targeted and drug delivery systems (TDDS) has received great attention thanks to the possibility to overcome the limitations of classical cancer chemotherapy, including targeting incapability, nonspecific action and, consequently, systemic toxicity. Thus, this research aims at using a novel design of Poly(N-isopropylacrylamide) p(NIPAM)-based microgels to specifically target cancer cells and avoid the healthy ones, which is expected to decrease or eliminate the side effects of chemotherapeutic drugs. Smart NIPAM-based microgels were functionalized with acrylic acid and coupled to folic acid (FA), targeting the folate receptors overexpressed by cancer cells and to the chemotherapeutic drug doxorubicin (Dox). The successful conjugation of FA and Dox was demonstrated by dynamic light scattering (DLS), Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), UV-VIS analysis, and differential scanning calorimetry (DSC). Furthermore, viability assay performed on cancer and healthy breast cells, suggested the microgels’ biocompatibility and the cytotoxic effect of the conjugated drug. On the other hand, the specific tumor targeting of synthetized microgels was demonstrated by a co-cultured (healthy and cancer cells) assay monitored using confocal microscopy and flow cytometry. Results suggest successful targeting of cancer cells and drug release. These data support the use of pNIPAM-based microgels as good candidates as TDDS

The Quality of Registration of Clinical Trials

BACKGROUND: Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. METHODS AND FINDINGS: A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. CONCLUSIONS: Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records

Selecting, refining and identifying priority Cochrane Reviews in health communication and participation in partnership with consumers and other stakeholders

Abstract : Background: Priority-setting partnerships between researchers and stakeholders (meaning consumers, health professionals and health decision-makers) may improve research relevance and value. The Cochrane Consumers and Communication Group (CCCG) publishes systematic reviews in 'health communication and participation', which includes concepts such as shared decision-making, patient-centred care and health literacy. We aimed to select and refine priority topics for systematic reviews in health communication and participation, and use these to identify five priority CCCG Cochrane Reviews. Methods: Twenty-eight participants (14 consumers, 14 health professionals/decision-makers) attended a 1-day workshop in Australia. Using large-group activities and voting, participants discussed, revised and then selected 12 priority topics from a list of 21 previously identified topics. In mixed small groups, participants refined these topics, exploring underlying problems, who they affect and potential solutions. Thematic analysis identified cross-cutting themes, in addition to key populations and potential interventions for future Cochrane Reviews. We mapped these against CCCG's existing review portfolio to identify five priority reviews. Results: Priority topics included poor understanding and implementation of patient-centred care by health services, the fact that health information can be a low priority for health professionals, communication and coordination breakdowns in health services, and inadequate consumer involvement in health service design. The four themes underpinning the topics were culture and organisational structures, health professional attitudes and assumptions, inconsistent experiences of care, and lack of shared understanding in the sector. Key populations for future reviews were described in terms of social health characteristics (e.g. people from indigenous or culturally and linguistically diverse backgrounds, elderly people, and people experiencing socioeconomic disadvantage) more than individual health characteristics. Potential interventions included health professional education, interventions to change health service/health professional culture and attitudes, and health service policies and standards. The resulting five priority Cochrane Reviews identified were improving end-of-life care communication, patient/family involvement in patient safety, improving future doctors' communication skills, consumer engagement strategies, and promoting patient-centred care. Conclusions: Stakeholders identified priority topics for systematic reviews associated with structural and cultural challenges underlying health communication and participation, and were concerned that issues of equity be addressed. Priority-setting with stakeholders presents opportunities and challenges for review producers

PRESENCE OF AVIAN INFLUENZA VIRUS IN WILD BIRDS IN THE WETLANDS OF PUERTO VIEJO, LIMA

El objetivo del estudio fue determinar la presencia del virus de influenza aviar (IA) en aves silvestres presentes en los Humedales de Puerto Viejo, en el departamento de Lima. Novecientas muestras de heces frescas de 18 especies de aves silvestres fueron colectadas desde abril de 2008 hasta febrero de 2009. Dichas muestras se analizaron mediante aislamiento viral en huevos embrionados de pollo SPF. Se logró aislar siete cepas de virus de IA de baja patogenicidad del subtipo H12N5 (seis cepas procedentes de la especie migratoria Arenaria interpres y una de la especie residente Fulica ardesiaca). La técnica de evaluación de riesgo mediante la simulación de Monte Carlo (programa @risk) indicó que la probabilidad de encontrar el virus de Influenza A en las aves silvestres de los Humedales de Puerto Viejo es de 0.88% con un intervalo de confianza de 0.15 a 2.53%. Los resultados demuestran que las aves silvestres de los Humedales de Puerto Viejo constituyen un reservorio para los virus de influenza aviar en el Perú.The objective of the study was to detect the presence of avian influenza (AI) virus in wild aquatic birds found in Puerto Viejo wetlands, Lima-Peru. Fresh faecal samples (n=900) from 18 species of wild birds were collected from April 2008 to February 2009. Samples were analyzed by virus isolation in SPF embryonated chicken eggs. Seven strains of low pathogenicity AI viruses subtype H12N5 were isolated; six from the migratory species Arenaria interpres, and one from the resident species Fulica ardesiaca. The technique of risk assessment using Monte Carlo Simulation (program @ risk) indicated that the probability of finding the AI virus in wild birds from Puerto Viejo wetlands was 0.88% with a confidence interval of 0.15 to 2.53%. The results of the study showed that wild birds from Puerto Viejo wetlands constitute a reservoir for avian influenza virus in Peru

Modulation of Mrp1 (ABCc1) and Pgp (ABCb1) by Bilirubin at the Blood-CSF and Blood-Brain Barriers in the Gunn Rat

Accumulation of unconjugated bilirubin (UCB) in the brain causes bilirubin encephalopathy. Pgp (ABCb1) and Mrp1 (ABCc1), highly expressed in the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) respectively, may modulate the accumulation of UCB in brain. We examined the effect of prolonged exposure to elevated concentrations of UCB on expression of the two transporters in homozygous, jaundiced (jj) Gunn rats compared to heterozygous, not jaundiced (Jj) littermates at different developmental stages (2, 9, 17 and 60 days after birth). BBB Pgp protein expression was low in both jj and Jj pups at 9 days (about 16–27% of adult values), despite the up-regulation in jj animals (2 and 1.3 fold higher than age matched Jj animals at P9 and P17–P60, respectively); Mrp1 protein expression was barely detectable. Conversely, at the BCSFB Mrp1 protein expression was rather high (60–70% of the adult values) in both jj and Jj at P2, but was markedly (50%) down-regulated in jj pups starting at P9, particularly in the 4th ventricle choroid plexuses: Pgp was almost undetectable. The Mrp1 protein down regulation was accompanied by a modest up-regulation of mRNA, suggesting a translational rather than a transcriptional inhibition. In vitro exposure of choroid plexus epithelial cells obtained from normal rats to UCB, also resulted in a down-regulation of Mrp1 protein. These data suggest that down-regulation of Mrp1 protein at the BSCFB, resulting from a direct effect of UCB on epithelial cells, may impact the Mrp1-mediated neuroprotective functions of the blood-cerebrospinal fluid barrier and actually potentiate UCB neurotoxicity

Protocol for the development of guidance for stakeholder engagement in health and healthcare guideline development and implementation

Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. METHODS: This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. DISCUSSION: We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health