Epidemiology and Reporting Characteristics of Systematic Reviews of Biomedical Research: A Cross-Sectional Study

BackgroundSystematic reviews (SRs) can help decision makers interpret the deluge of published biomedical literature. However, a SR may be of limited use if the methods used to conduct the SR are flawed, and reporting of the SR is incomplete. To our knowledge, since 2004 there has been no cross-sectional study of the prevalence, focus, and completeness of reporting of SRs across different specialties. Therefore, the aim of our study was to investigate the epidemiological and reporting characteristics of a more recent cross-section of SRs.ConclusionsAn increasing number of SRs are being published, and many are poorly conducted and reported. Strategies are needed to help reduce this avoidable waste in research.     

Deprescribing in Frail Older People: A Randomised Controlled Trial

Objectives

Deprescribing has been proposed as a way to reduce polypharmacy in frail older people. We aimed to reduce the number of medicines consumed by people living in residential aged care facilities (RACF). Secondary objectives were to explore the effect of deprescribing on survival, falls, fractures, hospital admissions, cognitive, physical, and bowel function, quality of life, and sleep.

Methods

Ninety-five people aged over 65 years living in four RACF in rural mid-west Western Australia were randomised in an open study. The intervention group (n = 47) received a deprescribing intervention, the planned cessation of non-beneficial medicines. The control group (n = 48) received usual care. Participants were monitored for twelve months from randomisation. Primary outcome was change in the mean number of unique regular medicines. All outcomes were assessed at baseline, six, and twelve months.

Results

Study participants had a mean age of 84.3±6.9 years and 52% were female. Intervention group participants consumed 9.6±5.0 and control group participants consumed 9.5±3.6 unique regular medicines at baseline. Of the 348 medicines targeted for deprescribing (7.4±3.8 per person, 78% of regular medicines), 207 medicines (4.4±3.4 per person, 59% of targeted medicines) were successfully discontinued. The mean change in number of regular medicines at 12 months was -1.9±4.1 in intervention group participants and +0.1±3.5 in control group participants (estimated difference 2.0±0.9, 95%CI 0.08, 3.8, p = 0.04). Twelve intervention participants and 19 control participants died within 12 months of randomisation (26% versus 40% mortality, p = 0.16, HR 0.60, 95%CI 0.30 to 1.22) There were no significant differences between groups in other secondary outcomes. The main limitations of this study were the open design and small participant numbers.

Conclusions

Deprescribing reduced the number of regular medicines consumed by frail older people living in residential care with no significant adverse effects on survival or other clinical outcomes.

Trial Registration

Australian New Zealand Clinical Trials Registry ACTRN12611000370909     

An ectopic expression screen reveals the protective and toxic effects of Drosophila seminal fluid proteins

In Drosophila melanogaster, seminal fluid regulates the reproductive and immune responses of mated females. Some seminal fluid proteins may provide protective functions to mated females, such as antimicrobial activity and/or stimulation of antimicrobial gene expression levels, while others appear to have negative effects, contributing to a "cost of mating." To identify seminal proteins that could participate in these phenomena, we used a systemic ectopic expression screen to test the effects on unmated females of proteins normally produced by the male accessory gland (Acps). Of the 21 ectopically expressed Acps that we tested for ability to assist in the clearance of a bacterial infection with Serratia marcescens, 3 Acps significantly reduced the bacterial counts of infected females, suggesting a protective role. Of the 23 Acps that we tested for toxicity, 3 were toxic, including one that has been implicated in the cost of mating in another study. We also tested ectopic expression females for other Acp-induced effects, but found no additional Acps that affected egg laying or receptivity upon ectopic expression.     

Proteomics demonstration that normal breast epithelial cells can induce apoptosis of breast cancer cells through insulin-like growth factor-binding protein-3 and maspin

Normal breast epithelial cells are known to exert an apoptotic effect on breast cancer cells, resulting in a potential paracrine inhibition of breast tumor development. In this study we purified and characterized the apoptosis-inducing factors secreted by normal breast epithelial cells. Conditioned medium was concentrated by ultrafiltration and separated on reverse phase Sep-Pak C18 and HPLC. The proapoptotic activity of eluted fractions was tested on MCF-7 breast cancer cells, and nano-LC-nano-ESI-MS/MS allowed the identification of insulin-like growth factor-binding protein-3 (IGFBP-3) and maspin as the proapoptotic factors produced by normal breast epithelial cells. Western blot analysis of conditioned media confirmed the specific secretion of IGFBP-3 and maspin by normal cells but not by breast cancer cells. Immunodepletion of IGFBP-3 and maspin completely abolished the normal cell-induced apoptosis of cancer cells, and recombinant proteins reproduced the effect of normal cell-conditioned medium on apoptosis of breast cancer cells. Together our results indicated that normal breast epithelial cells can induce apoptosis of breast cancer cells through IGFBP-3 and maspin. These findings provide a molecular hypothesis for the long observed inhibitory effect of normal surrounding cells on breast cancer development.     

Thermal stress and coral cover as drivers of coral disease outbreaks

Very little is known about how environmental changes such as increasing temperature affect disease dynamics in the ocean, especially at large spatial scales. We asked whether the frequency of warm temperature anomalies is positively related to the frequency of coral disease across 1,500 km of Australia's Great Barrier Reef. We used a new high-resolution satellite dataset of ocean temperature and 6 y of coral disease and coral cover data from annual surveys of 48 reefs to answer this question. We found a highly significant relationship between the frequencies of warm temperature anomalies and of white syndrome, an emergent disease, or potentially, a group of diseases, of Pacific reef-building corals. The effect of temperature was highly dependent on coral cover because white syndrome outbreaks followed warm years, but only on high (>50%) cover reefs, suggesting an important role of host density as a threshold for outbreaks. Our results indicate that the frequency of temperature anomalies, which is predicted to increase in most tropical oceans, can increase the susceptibility of corals to disease, leading to outbreaks where corals are abundant.     

Genetic variation,demographic history and phylogeography of tire track eel,Mastacembelus favus (Synbranchiformes: Mastacembelidae) in Southeast Asia

The complex climatic and geological history of Southeast Asia has been hypothesised to determine the most important aspects of the current phylogeographical structure and distribution of living organisms throughout the region. To test existing hypotheses, the genetic structure of the tire track eel, Mastacembelus favus, was investigated using 823 bp of mitochondrial DNA cytochrome b from 469 individuals from 51 localities encompassing its native range. The results classified all haplotypes into two major lineages, Lineage 1, which was further divided into Lineages 1a (lower Mekong, eastern Gulf of Thailand and Malay—Thai Peninsula), 1b (Banpakong River), 1c (Chao Phraya, Gulf of Thailand and Malay—Thai Peninsula) and 1d (Khlang Yai River), and Lineage 2, the upper reaches of the lower Mekong and the middle Mekong. Strong genetic discontinuities dated approximately 5 MYA were discovered in the Mekong with limited geographical overlap, suggesting a historically dissected drainage between two sections and species colonisation via different routes. The widespread Lineage 1 showed a strong signature of population expansion during the Pleistocene climate oscillation. Haplotype characteristics in the Malay—Thai Peninsula are hypothesised to result from postglacial dispersal from the Mekong and Chao Phraya through an extended Pleistocene drainage network.

     

Parasite cyclophilins and antiparasite activity of cyclosporin A

Cyclosporin A (CsA) was initially developed as an immunosuppressive drug. In the past several years, it has been shown to possess antiparasite activity independent of the immune system. It is not known how the drug exerts these antiparasite effects, or why it is stage and/or species specific. The answers may lie in the enzymatic function of cyclophilins. The cyclophilins are a growing family of proteins that exhibit peptidyl-prolyl cis-trans isomerase (PPiase) activity and bid CsA to varying degrees. PPiases have been shown to play a role in the folding of many essential proteins. Antony Page, Sanjay Kumar and Clotilde Carlow here review parasite cyclophilins and their association with CsA. The possible biological function of parasite cyclophilins and their potential role in future drug discovery are also discussed.