1,731 research outputs found
Generating real-world evidence on the quality use, benefits and safety of medicines in australia: History, challenges and a roadmap for the future
Australia spends more than $20 billion annually on medicines, delivering significant health benefits for the population. However, inappropriate prescribing and medicine use also result in harm to individuals and populations, and waste of precious health resources. Medication data linked with other routine collections enable evidence generation in pharmacoepidemiology; the science of quantifying the use, effectiveness and safety of medicines in real-world clinical practice. This review details the history of medicines policy and data access in Australia, the strengths of existing data sources, and the infrastructure and governance enabling and impeding evidence generation in the field. Currently, substantial gaps persist with respect to cohesive, contemporary linked data sources supporting quality use of medicines, effectiveness and safety research; exemplified by Aus-tralia’s limited capacity to contribute to the global effort in real-world studies of vaccine and dis-ease-modifying treatments for COVID-19. We propose a roadmap to bolster the discipline, and population health more broadly, underpinned by a distinct capability governing and streamlining access to linked data assets for accredited researchers. Robust real-world evidence generation requires current data roadblocks to be remedied as a matter of urgency to deliver efficient and equitable health care and improve the health and well-being of all Australians
Different approaches for dealing with rare variants in family-based genetic studies: application of a Genetic Analysis Workshop 17 problem
Rare variants are becoming the new candidates in the search for genetic variants that predispose individuals to a phenotype of interest. Their low prevalence in a population requires the development of dedicated detection and analytical methods. A family-based approach could greatly enhance their detection and interpretation because rare variants are nearly family specific. In this report, we test several distinct approaches for analyzing the information provided by rare and common variants and how they can be effectively used to pinpoint putative candidate genes for follow-up studies. The analyses were performed on the mini-exome data set provided by Genetic Analysis Workshop 17. Eight approaches were tested, four using the trait’s heritability estimates and four using QTDT models. These methods had their sensitivity, specificity, and positive and negative predictive values compared in light of the simulation parameters. Our results highlight important limitations of current methods to deal with rare and common variants, all methods presented a reduced specificity and, consequently, prone to false positive associations. Methods analyzing common variants information showed an enhanced sensibility when compared to rare variants methods. Furthermore, our limited knowledge of the use of biological databases for gene annotations, possibly for use as covariates in regression models, imposes a barrier to further research
Candidate gene analysis of ocular toxoplasmosis in Brazil: evidence for a role for toll-like receptor 9 (TLR9)
Effects of enamel matrix derivative and transforming growth factor-β1 on human osteoblastic cells
<p>Abstract</p> <p>Background</p> <p>Extracellular matrix proteins are key factors that influence the regenerative capacity of tissues. The objective of the present study was to evaluate the effects of enamel matrix derivative (EMD), TGF-β1, and the combination of both factors (EMD+TGF-β1) on human osteoblastic cell cultures.</p> <p>Methods</p> <p>Cells were obtained from alveolar bone of three adult patients using enzymatic digestion. Effects of EMD, TGF-β1, or a combination of both were analyzed on cell proliferation, bone sialoprotein (BSP), osteopontin (OPN) and alkaline phosphatase (ALP) immunodetection, total protein synthesis, ALP activity and bone-like nodule formation.</p> <p>Results</p> <p>All treatments significantly increased cell proliferation compared to the control group at 24 h and 4 days. At day 7, EMD group showed higher cell proliferation compared to TGF-β1, EMD + TGF-β1 and the control group. OPN was detected in the majority of the cells for all groups, whereas fluorescence intensities for ALP labeling were greater in the control than in treated groups; BSP was not detected in all groups. All treatments decreased ALP levels at 7 and 14 days and bone-like nodule formation at 21 days compared to the control group.</p> <p>Conclusions</p> <p>The exposure of human osteoblastic cells to EMD, TGF-β1 and the combination of factors <it>in vitro </it>supports the development of a less differentiated phenotype, with enhanced proliferative activity and total cell number, and reduced ALP activity levels and matrix mineralization.</p
Methods and challenges for the health impact assessment of vaccination programs in Latin America
Validation of a Persian version of the OIDP index
BACKGROUND: Measuring the impacts of oral conditions on quality of life is an important part of oral health needs assessment. For this purpose a variety of oral health-related quality of life instruments have been developed. To use a scale in a new context or with a different groups of people, it is necessary to re-establish its psychometric properties. The objectives of this study are to develop and test the reliability and validity of the Persian version of Oral Impacts on Daily Performances (OIDP) index. METHODS: The Persian version of OIDP index was developed through a linguistic translation exercise. The psychometric properties of the Persian version of OIDP were evaluated in terms of face, content, construct and criterion validity in addition to internal and test-retest reliability. A convenience sample of 285 working adults aged 20–50 living in Mashad was recruited (91% response rate) to evaluate the Persian version. RESULTS: The Persian version of OIDP had excellent validity and reliability charactersitics. Weighted Kappa was 0.91. Cronbachs alpha coefficient was 0.79. The index showed significant associations with self-rated oral and general health status, as well as perceived dental treatment needs, satisfaction with mouth and prevalence of pain in mouth (P < 0.001). 64.9% of subjects had an oral impact on their daily performances. The most prevalent performance affected was eating, followed by major work or role and sleeping. CONCLUSION: The Persian version of OIDP index is a valid and reliable measure for use in 20 to 50 year old working Iranians
Essential data variables for a minimum dataset for head and neck cancer trials and clinical research:HNCIG consensus recommendations and database
The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website
The Pioneer Anomaly
Radio-metric Doppler tracking data received from the Pioneer 10 and 11
spacecraft from heliocentric distances of 20-70 AU has consistently indicated
the presence of a small, anomalous, blue-shifted frequency drift uniformly
changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was
interpreted as a constant sunward deceleration of each particular spacecraft at
the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of
the Newton's gravitational inverse-square law has become known as the Pioneer
anomaly; the nature of this anomaly remains unexplained. In this review, we
summarize the current knowledge of the physical properties of the anomaly and
the conditions that led to its detection and characterization. We review
various mechanisms proposed to explain the anomaly and discuss the current
state of efforts to determine its nature. A comprehensive new investigation of
the anomalous behavior of the two Pioneers has begun recently. The new efforts
rely on the much-extended set of radio-metric Doppler data for both spacecraft
in conjunction with the newly available complete record of their telemetry
files and a large archive of original project documentation. As the new study
is yet to report its findings, this review provides the necessary background
for the new results to appear in the near future. In particular, we provide a
significant amount of information on the design, operations and behavior of the
two Pioneers during their entire missions, including descriptions of various
data formats and techniques used for their navigation and radio-science data
analysis. As most of this information was recovered relatively recently, it was
not used in the previous studies of the Pioneer anomaly, but it is critical for
the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living
Reviews in Relativit
Increased prevalence of methicillin-resistant Staphylococcus aureus nasal colonization in household contacts of children with community acquired disease
<p>Abstract</p> <p>Background</p> <p>To measure Methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) nasal colonization prevalence in household contacts of children with current community associated (CA)-MRSA infections (study group) in comparison with a group of household contacts of children without suspected <it>Staphylococcus aureus </it>infection (a control group).</p> <p>Methods</p> <p>This is a cross sectional study. Cultures of the anterior nares were taken. Relatedness of isolated strains was tested using pulse field gel electrophoresis (PFGE).</p> <p>Results</p> <p>The prevalence of MRSA colonization in the study group was significantly higher than in the control group (18/77 (23%) vs 3/77 (3.9%); p ≤ 0.001). The prevalence of SA colonization was 28/77 (36%) in the study group and 16/77 (21%) in the control group (p = 0.032). The prevalence of SA nasal colonization among patients was 6/24 (25%); one with methicillin-susceptible <it>S. aureus </it>(MSSA) and 5 with MRSA. In the study (patient) group, 14/24 (58%) families had at least one household member who was colonized with MRSA compared to 2/29 (6.9%) in the control group (p = 0.001). Of 69 total isolates tested by PFGE, 40 (58%) were related to USA300. Panton-Valetine leukocidin (PVL) genes were detected in 30/52 (58%) tested isolates. Among the families with ≥1 contact colonized with MRSA, similar PFGE profiles were found between the index patient and a contact in 10/14 families.</p> <p>Conclusions</p> <p>Prevalence of asymptomatic nasal carriage of MRSA is higher among household contacts of patients with CA-MRSA disease than control group. Decolonizing such carriers may help prevent recurrent CA-MRSA infections.</p
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