Background
Decision aids are interventions that support patients by making their decisions explicit, providing information about options and associated benefits/harms, and helping clarify congruence ...between decisions and personal values.
Objectives
To assess the effects of decision aids in people facing treatment or screening decisions.
Search methods
Updated search (2012 to April 2015) in CENTRAL; MEDLINE; Embase; PsycINFO; and grey literature; includes CINAHL to September 2008.
Selection criteria
We included published randomized controlled trials comparing decision aids to usual care and/or alternative interventions. For this update, we excluded studies comparing detailed versus simple decision aids.
Data collection and analysis
Two reviewers independently screened citations for inclusion, extracted data, and assessed risk of bias. Primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were attributes related to the choice made and the decision‐making process.
Secondary outcomes were behavioural, health, and health system effects.
We pooled results using mean differences (MDs) and risk ratios (RRs), applying a random‐effects model. We conducted a subgroup analysis of studies that used the patient decision aid to prepare for the consultation and of those that used it in the consultation. We used GRADE to assess the strength of the evidence.
Main results
We included 105 studies involving 31,043 participants. This update added 18 studies and removed 28 previously included studies comparing detailed versus simple decision aids. During the 'Risk of bias' assessment, we rated two items (selective reporting and blinding of participants/personnel) as mostly unclear due to inadequate reporting. Twelve of 105 studies were at high risk of bias.
With regard to the attributes of the choice made, decision aids increased participants' knowledge (MD 13.27/100; 95% confidence interval (CI) 11.32 to 15.23; 52 studies; N = 13,316; high‐quality evidence), accuracy of risk perceptions (RR 2.10; 95% CI 1.66 to 2.66; 17 studies; N = 5096; moderate‐quality evidence), and congruency between informed values and care choices (RR 2.06; 95% CI 1.46 to 2.91; 10 studies; N = 4626; low‐quality evidence) compared to usual care.
Regarding attributes related to the decision‐making process and compared to usual care, decision aids decreased decisional conflict related to feeling uninformed (MD −9.28/100; 95% CI −12.20 to −6.36; 27 studies; N = 5707; high‐quality evidence), indecision about personal values (MD −8.81/100; 95% CI −11.99 to −5.63; 23 studies; N = 5068; high‐quality evidence), and the proportion of people who were passive in decision making (RR 0.68; 95% CI 0.55 to 0.83; 16 studies; N = 3180; moderate‐quality evidence).
Decision aids reduced the proportion of undecided participants and appeared to have a positive effect on patient‐clinician communication. Moreover, those exposed to a decision aid were either equally or more satisfied with their decision, the decision‐making process, and/or the preparation for decision making compared to usual care.
Decision aids also reduced the number of people choosing major elective invasive surgery in favour of more conservative options (RR 0.86; 95% CI 0.75 to 1.00; 18 studies; N = 3844), but this reduction reached statistical significance only after removing the study on prophylactic mastectomy for breast cancer gene carriers (RR 0.84; 95% CI 0.73 to 0.97; 17 studies; N = 3108). Compared to usual care, decision aids reduced the number of people choosing prostate‐specific antigen screening (RR 0.88; 95% CI 0.80 to 0.98; 10 studies; N = 3996) and increased those choosing to start new medications for diabetes (RR 1.65; 95% CI 1.06 to 2.56; 4 studies; N = 447). For other testing and screening choices, mostly there were no differences between decision aids and usual care.
The median effect of decision aids on length of consultation was 2.6 minutes longer (24 versus 21; 7.5% increase). The costs of the decision aid group were lower in two studies and similar to usual care in four studies. People receiving decision aids do not appear to differ from those receiving usual care in terms of anxiety, general health outcomes, and condition‐specific health outcomes. Studies did not report adverse events associated with the use of decision aids.
In subgroup analysis, we compared results for decision aids used in preparation for the consultation versus during the consultation, finding similar improvements in pooled analysis for knowledge and accurate risk perception. For other outcomes, we could not conduct formal subgroup analyses because there were too few studies in each subgroup.
Authors' conclusions
Compared to usual care across a wide variety of decision contexts, people exposed to decision aids feel more knowledgeable, better informed, and clearer about their values, and they probably have a more active role in decision making and more accurate risk perceptions. There is growing evidence that decision aids may improve values‐congruent choices. There are no adverse effects on health outcomes or satisfaction. New for this updated is evidence indicating improved knowledge and accurate risk perceptions when decision aids are used either within or in preparation for the consultation. Further research is needed on the effects on adherence with the chosen option, cost‐effectiveness, and use with lower literacy populations.
Capturing variability in use of commercial technologies by autistic children can inform future learning and support technology design. Survey data were collected from parents (
n
= 388) in the UK, ...Spain, and Belgium, and includes information about individuals with a range of ages and ability levels. We found a comparable pattern of access and usage across age groups, though higher reading and language ability was linked to use of more devices and interfaces. Reported worries about technology correlated with longer time spent using technology. Autistic children use mainstream technologies for a broad range of recreational uses. The data suggest that technologies developed with therapeutic goals in mind may need to achieve a high standard of design to engage users.
gamma delta T cells play important roles in bridging innate and adaptive immunity, but their recognition mechanisms remain poorly understood. Human gamma delta T cells of the V delta 1 subset ...predominate in intestinal epithelia and respond to MICA and MICB (MHC class I chain-related, A and B; MIC) self-antigens, mediating responses to tumorigenesis or viral infection. The crystal structure of an MIC-reactive V delta 1 gamma delta T-cell receptor (TCR) showed expected overall structural homology to antibodies, alpha beta , and other gamma delta TCRs, but complementary determining region conformations and conservation of V delta 1 use revealed an uncharacteristically flat potential binding surface. MIC, likewise, serves as a ligand for the activating immunoreceptor natural killer group 2, D (NKG2D), also expressed on gamma delta T cells. Although MIC recognition drives both the TCR-dependent stimulatory and NKG2D-dependent costimulatory signals necessary for activation, interaction analyses showed that MIC binding by the two receptors was mutually exclusive. Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of gamma delta T-cell/target cell interfaces.
Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated. This is achieved through a variety of iron-binding proteins including transferrin and ...ferritin. During infection, bacteria acquire much of their iron from the host by synthesizing siderophores that scavenge iron and transport it into the pathogen. We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5). Here, we show that this event is pivotal in the innate immune response to bacterial infection. Upon encountering invading bacteria the Toll-like receptors on immune cells stimulate the transcription, translation and secretion of lipocalin 2; secreted lipocalin 2 then limits bacterial growth by sequestrating the iron-laden siderophore. Our finding represents a new component of the innate immune system and the acute phase response to infection.
Broadly cross-reactive monoclonal antibodies define epitopes for vaccine development against HIV and other highly mutable viruses. Crystal structures are available for several such antibody-epitope ...complexes, but methods are needed to translate that structural information into immunogens that re-elicit similar antibodies. We describe a general computational method to design epitope-scaffolds in which contiguous structural epitopes are transplanted to scaffold proteins for conformational stabilization and immune presentation. Epitope-scaffolds designed for the poorly immunogenic but conserved HIV epitope 4E10 exhibited high epitope structural mimicry, bound with higher affinities to monoclonal antibody (mAb) 4E10 than the cognate peptide, and inhibited HIV neutralization by HIV+ sera. Rabbit immunization with an epitope-scaffold induced antibodies with structural specificity highly similar to mAb 4E10, an important advance toward elicitation of neutralizing activity. The results demonstrate that computationally designed epitope-scaffolds are valuable as structure-specific serological reagents and as immunogens to elicit antibodies with predetermined structural specificity.
► Epitope-scaffolds are computationally designed to stabilize epitope structures ► Epitope-scaffolds for the HIV epitope 4E10 accurately mimic the epitope structure ► 4e10 epitope-scaffolds bind mAb 4E10 up to 1000-fold more tightly than 4E10 peptide ► A 4E10 epitope-scaffold elicits antibodies with specificity similar to mAb 4E10
The process of antibody ontogeny typically improves affinity, on-rate, and thermostability, narrows polyspecificity, and rigidifies the combining site to the conformer optimal for binding from the ...broader ensemble accessible to the precursor. However, many broadly-neutralizing anti-HIV antibodies incorporate unusual structural elements and recognition specificities or properties that often lead to autoreactivity. The ontogeny of 4E10, an autoreactive antibody with unexpected combining site flexibility, was delineated through structural and biophysical comparisons of the mature antibody with multiple potential precursors. 4E10 gained affinity primarily by off-rate enhancement through a small number of mutations to a highly conserved recognition surface. Controverting the conventional paradigm, the combining site gained flexibility and autoreactivity during ontogeny, while losing thermostability, though polyspecificity was unaffected. Details of the recognition mechanism, including inferred global effects due to 4E10 binding, suggest that neutralization by 4E10 may involve mechanisms beyond simply binding, also requiring the ability of the antibody to induce conformational changes distant from its binding site. 4E10 is, therefore, unlikely to be re-elicited by conventional vaccination strategies.
Background
Decision Aids (DAs) effectively translate medical evidence for patients but are not routinely used in clinical practice. Little is known about how DAs are used during patient‐clinician ...encounters.
Objective
To characterize the content and communicative function of high‐quality DAs during diagnostic clinic visits for prostate cancer.
Participants
252 men newly diagnosed with localized prostate cancer who had received a DA, 45 treating physicians at 4 US Veterans Administration urology clinics.
Methods
Qualitative analysis of transcribed audio recordings was used to inductively develop categories capturing content and function of all direct references to DAs (booklet talk). The presence or absence of any booklet talk per transcript was also calculated.
Results
Booklet talk occurred in 55% of transcripts. Content focused on surgical procedures (36%); treatment choice (22%); and clarifying risk classification (17%). The most common function of booklet talk was patient corroboration of physicians’ explanations (42%), followed by either physician or patient acknowledgement that the patient had the booklet. Codes reflected the absence of DA use for shared decision‐making. In regression analysis, predictors of booklet talk were fewer years of patient education (P = .027) and more time in the encounter (P = .027). Patient race, DA type, time reading the DA, physician informing quality and physician age did not predict booklet talk.
Conclusions
Results show that good decision aids, systematically provided to patients, appeared to function not to open up deliberations about how to balance benefits and harms of competing treatments, but rather to allow patients to ask narrow technical questions about recommended treatments.
Siderocalin (also lipocalin 2, NGAL or 24p3) binds iron as complexes with specific siderophores, which are low molecular weight, ferric ion-specific chelators. In innate immunity, siderocalin slows ...the growth of infecting bacteria by sequestering bacterial ferric siderophores. Siderocalin also binds simple catechols, which can serve as siderophores in the damaged urinary tract. Siderocalin has also been proposed to alter cellular iron trafficking, for instance, driving apoptosis through iron efflux via BOCT. An endogenous siderophore composed of gentisic acid (2,5-dihydroxybenzoic acid) substituents was proposed to mediate cellular efflux. However, binding studies reported herein contradict the proposal that gentisic acid forms high-affinity ternary complexes with siderocalin and iron, or that gentisic acid can serve as an endogenous siderophore at neutral pH. We also demonstrate that siderocalin does not induce cellular iron efflux or stimulate apoptosis, questioning the role siderocalin plays in modulating iron metabolism.
Siderocalin, a member of the lipocalin family of binding proteins, is found in neutrophil granules, uterine secretions, and at markedly elevated levels in serum and synovium during bacterial ...infection; it is also secreted from epithelial cells in response to inflammation or tumorigenesis. Identification of high-affinity ligands, bacterial catecholate-type siderophores (such as enterochelin), suggested a possible function for siderocalin: an antibacterial agent, complementing the general antimicrobial innate immune system iron-depletion strategy, sequestering iron as ferric siderophore complexes. Supporting this hypothesis, siderocalin is a potent bacteriostatic agent in vitro under iron-limiting conditions and, when knocked out, renders mice remarkably susceptible to bacterial infection. Here we show that siderocalin also binds soluble siderophores of mycobacteria, including
M. tubercu losis: carboxymycobactins. Siderocalin employs a degenerate recognition mechanism to cross react with these dissimilar types of siderophores, broadening the potential utility of this innate immune defense.
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