Assessing harmful effects in systematic reviews.

BACKGROUND: Balanced decisions about health care interventions require reliable evidence on harms as well as benefits. Most systematic reviews focus on efficacy and randomised trials, for which the methodology is well established. Methods to systematically review harmful effects are less well developed and there are few sources of guidance for researchers. We present our own recent experience of conducting systematic reviews of harmful effects and make suggestions for future practice and further research. METHODS: We described and compared the methods used in three systematic reviews. Our evaluation focused on the review question, study designs and quality assessment. RESULTS: One review question focused on providing information on specific harmful effects to furnish an economic model, the other two addressed much broader questions. All three reviews included randomised and observational data, although each defined the inclusion criteria differently. Standard methods were used to assess study quality. Various practical problems were encountered in applying the study design inclusion criteria and assessing quality, mainly because of poor study design, inadequate reporting and the limitations of existing tools. All three reviews generated a large volume of work that did not yield much useful information for health care decision makers. The key areas for improvement we identified were focusing the review question and developing methods for quality assessment of studies of harmful effects. CONCLUSIONS: Systematic reviews of harmful effects are more likely to yield information pertinent to clinical decision-making if they address a focused question. This will enable clear decisions to be made about the type of research to include in the review. The methodology for assessing the quality of harmful effects data in systematic reviews requires further development

Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century

The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis

Impacts of changing climate on the non-indigenous invertebrates in the northern Baltic Sea by end of the twenty-first century

Biological invasions coupled with climate change drive changes in marine biodiversity. Warming climate and changes in hydrology may either enable or hinder the spread of non-indigenous species (NIS) and little is known about how climate change modifies the richness and impacts of NIS in specific sea areas. We calculated from climate change simulations (RCO-SCOBI model) the changes in summer time conditions which northern Baltic Sea may to go through by the end of the twenty-first century, e.g., 2-5 A degrees C sea surface temperature rise and even up to 1.75 unit decrease in salinity. We reviewed the temperature and salinity tolerances (i.e., physiological tolerances and occurrence ranges in the field) of pelagic and benthic NIS established in-or with dispersal potential to-the northern Baltic Sea, and assessed how climate change will likely affect them. Our findings suggest a future decrease in barnacle larvae and an increase in Ponto-Caspian cladocerans in the pelagic community. In benthos, polychaetes, gastropods and decapods may become less abundant. By contrast, dreissenid bivalves, amphipods and mysids are expected to widen their distribution and increase in abundance in the coastal areas of the northern Baltic Sea. Potential salinity decrease acts as a major driver for NIS biogeography in the northern Baltic Sea, but temperature increase and extended summer season allow higher reproduction success in bivalves, zooplankton, amphipods and mysids. Successful NIS, i.e., coastal crustacean and bivalve species, pose a risk to native biota, as many of them have already demonstrated harmful effects in the Baltic Sea