Healthcare professionals frequently communicate the benefits of treatments as a relative risk reduction (RRR) in the likelihood of an event occurring. Here we evaluated whether presenting the ...benefits of osteoporosis treatment as a RRR in fractures compared with an absolute risk reduction (ARR) changed the patient’s attitudes towards accepting treatment. We surveyed 160 individuals attending a specialised osteoporosis clinic for face-to-face consultations between May 2018 and Jan 2021. They were presented with information on RRR for the treatment being considered followed by ARR and after each question were asked about how likely they would be to start treatment on a 5-point scale (1 = very likely, 5 = very unlikely). Participants were less likely to accept treatment when it was presented as ARR (mean score 2.02
vs.
2.67,
p
< 0.001, 95% CI for difference − 0.82 vs − 0.47) and thirty-eight participants (23.7%) declined treatment with knowledge of their ARR when they would have accepted the same treatment based on the RRR. Individuals who declined treatment had a lower 5-year risk of fracture than those who accepted treatment (9.0 vs. 12.5%,
p
< 0.001, 95% CI − 5.0 to − 1.6) and as fracture risk decreased, the participant was less likely to accept treatment (Spearman
r
− 0.32, 95% CI − 0.46 to − 0.17,
p
≤ 0.001). Whilst presentation of data as ARR more accurately reflects individual benefit and helps facilitate shared decision-making, clinicians should be aware that this will lead to a proportion of patients with lower fracture risk declining treatment for osteoporosis.
Summary Background Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is ...increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. Methods We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11 009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42 938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. Findings We identified five genome-wide significant loci (binomial test p≤5·0×10−8 ) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 95% CI 1·08–1·16; p=7·24×10−11 ), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3 . Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2 , chromosome 6 between FILIP1 and SENP6 , chromosome 12 close to KLHDC5 and PTHLH , and in another region of chromosome 12 close to CHST11 . One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight—a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. Interpretation Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention. Funding arcOGEN was funded by a special purpose grant from Arthritis Research UK.
African trypanosomes are devastating human and animal pathogens. Trypanosoma brucei rhodesiense and T. b. gambiense subspecies cause the fatal human disease known as African sleeping sickness. It is ...estimated that several hundred thousand new infections occur annually and the disease is fatal if untreated. T. brucei is transmitted by the tsetse fly and alternates between bloodstream-form and insect-form life cycle stages that are adapted to survive in the mammalian host and the insect vector, respectively. The importance of the flagellum for parasite motility and attachment to the tsetse fly salivary gland epithelium has been appreciated for many years. Recent studies have revealed both conserved and novel features of T. brucei flagellum structure and composition, as well as surprising new functions that are outlined here. These discoveries are important from the standpoint of understanding trypanosome biology and identifying novel drug targets, as well as for advancing our understanding of fundamental aspects of eukaryotic flagellum structure and function.
Purpose:
Local governments can implement food service guideline (FSG) policies, which, in large cities, may reach millions of people. This study identified FSG policies among the 20 largest US cities ...and analyzed them for key FSG policy attributes.
Design:
Quantitative research.
Setting:
Local government facilities.
Participants:
Twenty largest US cities.
Measures:
Frequency of FSG policies and percent alignment to tool.
Analysis:
Using municipal legal code libraries and other data sources, FSG policies enacted as of December 31, 2016, were identified. Full-text reviews were conducted of identified policies to determine whether they met inclusion criteria. Included policies were analyzed for key policy attributes specific to nutrition, behavioral design, implementation, and facility efficiency.
Results:
Searches identified 469 potential FSG policies, of which 6 policies across 5 cities met inclusion criteria. Five policies met a majority of criteria assessed by the classification tool. Overall alignment to the tool ranged from 17% to 88%. Of the 6 policies, 5 met a majority of the nutrition attributes and 5 met at least 50% of attributes associated with implementation. No policies met the attributes associated with facility efficiency.
Conclusion:
The FSG policies were identified in 5 of the 20 US cities. Policy alignment was high for nutrition and implementation attributes. This analysis suggests that when cities adopt FSG policies, many develop policies that align with key policy attributes. These policies can serve as models for other jurisdictions to create healthier food access through FSGs.
Purpose:
Food service guideline (FSG) policies can impact millions of daily meals sold or provided to government employees, patrons, and institutionalized persons. This study describes a ...classification tool to assess FSG policy attributes and uses it to rate FSG policies.
Design:
Quantitative content analysis.
Setting:
State government facilities in the United States.
Participants:
Participants were from 50 states and District of Columbia in the United States.
Measures:
Frequency of FSG policies and percentage alignment to tool.
Analysis:
State-level policies were identified using legal research databases to assess bills, statutes, regulations, and executive orders proposed or adopted by December 31, 2014. Full-text reviews were conducted to determine inclusion. Included policies were analyzed to assess attributes related to nutrition, behavioral supports, and implementation guidance.
Results:
A total of 31 policies met the inclusion criteria; 15 were adopted. Overall alignment ranged from 0% to 86%, and only 10 policies aligned with a majority of the FSG policy attributes. Western states had the most FSG policies proposed or adopted (11 policies). The greatest number of FSG policies were proposed or adopted (8 policies) in 2011, followed by the years 2013 and 2014.
Conclusion:
The FSG policies proposed or adopted through 2014 that intended to improve the food and beverage environment on state government property vary considerably in their content. This analysis offers baseline data on the FSG landscape and information for future FSG policy assessments.
Cilia and flagella are highly conserved, complex organelles involved in a variety of important functions. Flagella are required for motility of several human pathogens and ciliary defects lead to a ...variety of fatal and debilitating human diseases. Many of the major structural components of cilia and flagella are known, but little is known about regulation of flagellar beat. Trypanosoma brucei, the causative agent of African sleeping sickness, provides an excellent model for studying flagellar motility. We have used comparative genomics to identify a core group of 50 genes unique to organisms with motile flagella. These genes, referred to as T. brucei components of motile flagella (TbCMF) include 30 novel genes, and human homologues of many of the TbCMF genes map to loci associated with human ciliary diseases. To characterize TbCMF protein function we used RNA interference to target 41 TbCMF genes. Sedimentation assays and direct observation demonstrated clear motility defects in a majority of these knockdown mutants. Epitope tagging, fluorescence localization and biochemical fractionation demonstrated flagellar localization for several TbCMF proteins. Finally, ultrastructural analysis identified a family of novel TbCMF proteins that function to maintain connections between outer doublet microtubules, suggesting that they are the first identified components of nexin links. Overall, our results provide insights into the workings of the eukaryotic flagellum, identify several novel human disease gene candidates, reveal unique aspects of the trypanosome flagellum and underscore the value of T. brucei as an experimental system for studying flagellar biology.
Purpose
Definitions of acute respiratory distress syndrome (ARDS) include radiographic criteria, but there are concerns about reliability and prognostic relevance. This study aimed to evaluate the ...independent relationship between chest imaging and mortality and examine the inter-rater variability of interpretations of chest radiographs (CXR) in pediatric ARDS (PARDS).
Methods
Prospective, international observational study in children meeting Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria for PARDS, which requires new infiltrate(s) consistent with pulmonary parenchymal disease, without mandating bilateral infiltrates. Mortality analysis focused on the entire cohort, whereas inter-observer variability used a subset of patients with blinded, simultaneous interpretation of CXRs by intensivists and radiologists.
Results
Bilateral infiltrates and four quadrants of alveolar consolidation were associated with mortality on a univariable basis, using CXRs from 708 patients with PARDS. For patients on either invasive (IMV) or non-invasive ventilation (NIV) with PaO
2
/FiO
2
(PF) ratios (or SpO
2
/FiO
2
(SF) ratio equivalent) > 100, neither bilateral infiltrates (OR 1.3 (95% CI 0.68, 2.5),
p
= 0.43), nor 4 quadrants of alveolar consolidation (OR 1.6 (0.85, 3),
p
= 0.14) were associated with mortality. For patients with PF ≤ 100, bilateral infiltrates (OR 3.6 (1.4, 9.4),
p
= 0.01) and four quadrants of consolidation (OR 2.0 (1.14, 3.5),
p
= 0.02) were associated with higher mortality. A subset of 702 CXRs from 233 patients had simultaneous interpretations. Interobserver agreement for bilateral infiltrates and quadrants was “slight” (kappa 0.31 and 0.33). Subgroup analysis showed agreement did not differ when stratified by PARDS severity but was slightly higher for children with chronic respiratory support (kappa 0.62), NIV at PARDS diagnosis (kappa 0.53), age > 10 years (kappa 0.43) and fluid balance > 40 ml/kg (kappa 0.48).
Conclusion
Bilateral infiltrates and quadrants of alveolar consolidation are associated with mortality only for those with PF ratio ≤ 100, although there is high- inter-rater variability in these chest-x ray parameters.
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