Evaluating CollaboRATE in a Clinical Setting: Analysis of Mode Effects on Scores, Response Rates and Costs of Data Collection

Shared decision-making (SDM) has become a policy priority, yet its implementation is not routinely assessed. To address this gap we tested the delivery of CollaboRATE, a 3-item patient reported experience measure of SDM, via multiple survey modes.To assess CollaboRATE response rates and respondent characteristics across different modes of administration, impact of mode and patient characteristics on SDM performance and cost of administration per response in a real-world primary care practice.Observational study design, with repeated assessment of SDM performance using CollaboRATE in a primary care clinic over 15 months of data collection. Different modes of administration were introduced sequentially including paper, patient portal, interactive voice response (IVR) call, text message and tablet computer.Consecutive patients ≥18 years, or parents/guardians of patients \u3c18 years, visiting participating primary care clinicians.CollaboRATE assesses three core SDM tasks: (1) explanation about health issues, (2) elicitation of patient preferences and (3) integration of patient preferences into decisions. Responses to each item range from 0 (no effort was made) to 9 (every effort was made). CollaboRATE scores are calculated as the proportion of participants who report a score of nine on each of the three CollaboRATE questions.Scores were sensitive to mode effects: the paper mode had the highest average score (81%) and IVR had the lowest (61%). However, relative clinician performance rankings were stable across the different data collection modes used. Tablet computers administered by research staff had the highest response rate (41%), although this approach was costly. Clinic staff giving paper surveys to patients as they left the clinic had the lowest response rate (12%).CollaboRATE can be introduced using multiple modes of survey delivery while producing consistent clinician rankings. This may allow routine assessment and benchmarking of clinician and clinic SDM performance

Presenting quantitative information about decision outcomes: a risk communication primer for patient decision aid developers

Abstract Background Making evidence-based decisions often requires comparison of two or more options. Research-based evidence may exist which quantifies how likely the outcomes are for each option. Understanding these numeric estimates improves patients’ risk perception and leads to better informed decision making. This paper summarises current “best practices” in communication of evidence-based numeric outcomes for developers of patient decision aids (PtDAs) and other health communication tools. Method An expert consensus group of fourteen researchers from North America, Europe, and Australasia identified eleven main issues in risk communication. Two experts for each issue wrote a “state of the art” summary of best evidence, drawing on the PtDA, health, psychological, and broader scientific literature. In addition, commonly used terms were defined and a set of guiding principles and key messages derived from the results. Results The eleven key components of risk communication were: 1) Presenting the chance an event will occur; 2) Presenting changes in numeric outcomes; 3) Outcome estimates for test and screening decisions; 4) Numeric estimates in context and with evaluative labels; 5) Conveying uncertainty; 6) Visual formats; 7) Tailoring estimates; 8) Formats for understanding outcomes over time; 9) Narrative methods for conveying the chance of an event; 10) Important skills for understanding numerical estimates; and 11) Interactive web-based formats. Guiding principles from the evidence summaries advise that risk communication formats should reflect the task required of the user, should always define a relevant reference class (i.e., denominator) over time, should aim to use a consistent format throughout documents, should avoid “1 in x” formats and variable denominators, consider the magnitude of numbers used and the possibility of format bias, and should take into account the numeracy and graph literacy of the audience. Conclusion A substantial and rapidly expanding evidence base exists for risk communication. Developers of tools to facilitate evidence-based decision making should apply these principles to improve the quality of risk communication in practice.http://deepblue.lib.umich.edu/bitstream/2027.42/116070/1/12911_2013_Article_751.pd

Epifania, recriação e ressentimento: fragmentos narrativos sobre a experiência da viagem na imigração italiana no Brasil

L'expérience du voyage dans le processus de l'immigration marque le premier contact avec l'inconnu. L'aventure de la traversée de l'océan signifie par conséquent l'abandon du seul monde tangible. Le nouveau monde va se dévoiler à l'émigrant au fur et à mesure que le navire avance en mer, en un mélange de représentations produites avant le départ et de nouvelles “idées-images” que l'expérience elle-même du voyage contribue à élaborer en continu. Au cours de ce processus, la lecture de "Sull'Oceano" d’Edmondo De Amicis permet une immersion dans ce monde fragmentaire d'images et des récits que l'émigrant va produire. Il tente par ce biais de comprendre sa propre expérience et son existence, en un monde entrecroisé de différentes expressions de la sensibilité. Lê nouveau monde se révèle, souvenir tout à la fois d’une terre que l’on a abandonnée et recréation d'une représentation pacificatrice

Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.

A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults.This work was supported by the following grants and fellowships: Biotechnology and Biological Sciences Research Council, UK (BB/M012494/1) to V.K.R. and (BB/G00711/X/1) to V.K.R. and C.G.; and a Research Council UK Academic Fellowship to M.L.H. R.L. is supported by EU-FP7 BLUEPRINT. S.E.O. is supported by the British Heart Foundation (FS/12/64/30001) and the Medical Research Council (MC_UU_12012/4). This research used Queen Mary’s MidPlus computational facilities, supported by Queen Mary University of London Research-IT and funded by Engineering and Physical Sciences Research Council grant EP/K000128/1. We thank King’s College London FWB Genomics Centre and Barts and The London Genome Centre for performing high-throughput sequencing.This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via http://dx.doi.org/10.1126/science.aaf704

A comparative analysis of recombinant Fab and full‐length antibody production in Chinese hamster ovary cells

Monoclonal antibodies are the leading class of biopharmaceuticals in terms of numbers approved for therapeutic purposes. Antigen‐binding fragments (Fab) are also used as biotherapeutics and used widely in research applications. The dominant expression systems for full‐length antibodies are mammalian cell‐based, whereas for Fab molecules the preference has been an expression in bacterial systems. However, advances in CHO and downstream technologies make mammalian systems an equally viable option for small‐ and large‐scale Fab production. Using a panel of full‐length IgG antibodies and their corresponding Fab pair with different antigen specificities, we investigated the impact of the IgG and Fab molecule format on production from Chinese hamster ovary (CHO) cells and assessed the cellular capability to process and produce these formats. The full‐length antibody format resulted in the recovery of fewer mini‐pools posttransfection when compared to the corresponding Fab fragment format that could be interpreted as indicative of a greater overall burden on cells. Antibody‐producing cell pools that did recover were subsequently able to achieve higher volumetric protein yields (mg/L) and specific productivity than the corresponding Fab pools. Importantly, when the actual molecules produced per cell of a given format was considered (as opposed to mass), CHO cells produced a greater number of Fab molecules per cell than obtained with the corresponding IgG, suggesting that cells were more efficient at making the smaller Fab molecule. Analysis of cell pools showed that gene copy number was not correlated to the subsequent protein production. The amount of mRNA correlated with secreted Fab production but not IgG, whereby posttranscriptional processes act to limit antibody production. In summary, we provide the first comparative description of how full‐length IgG and Fab antibody formats impact on the outcomes of a cell line construction process and identify potential limitations in their production that could be targeted for engineering increases in the efficiency in the manufacture of these recombinant antibody formats

Using CollaboRATE, a brief patient‐reported measure of shared decision making: Results from three clinical settings in the United States

Abstract Introduction: CollaboRATE is a brief patient survey focused on shared decision making. This paper aims to (i) provide insight on facilitators and challenges to implementing a real‐time patient survey and (ii) evaluate CollaboRATE scores and response rates across multiple clinical settings with varied patient populations. Method All adult patients at three United States primary care practices were eligible to complete CollaboRATE post‐visit. To inform key learnings, we aggregated all mentions of unanticipated decisions, problems and administration errors from field notes and email communications. Mixed‐effects logistic regression evaluated the impact of site, clinician, patient age and patient gender on the CollaboRATE score. Results: While CollaboRATE score increased only slightly with increasing patient age (OR 1.018, 95% CI 1.014‐1.021), female patient gender was associated with significantly higher CollaboRATE scores (OR 1.224, 95% CI 1.073‐1.397). Clinician also predicts CollaboRATE score (random effect variance 0.146). Site‐specific factors such as clinical workflow and checkout procedures play a key role in successful in‐clinic implementation and are significantly related to CollaboRATE scores, with Site 3 scoring significantly higher than Site 1 (OR 1.759, 95% CI 1.216 to 2.545) or Site 2 (z=−2.71, 95% CI −1.114 to −0.178). Discussion This study demonstrates that CollaboRATE can be used in diverse primary care settings. A clinic's workflow plays a crucial role in implementation. Patient experience measurement risks becoming a burden to both patients and administrators. Episodic use of short measurement tools could reduce this burden

A comparative analysis of recombinant Fab and full‐length antibody production in Chinese hamster ovary cells

From Wiley via Jisc Publications RouterHistory: received 2021-06-18, rev-recd 2021-08-31, accepted 2021-09-12, pub-electronic 2021-10-06Article version: VoRPublication status: PublishedFunder: UCB UK; Id: http://dx.doi.org/10.13039/100011111Funder: Biotechnology and Biological Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/R001731/1, BB/R002096/1Abstract: Monoclonal antibodies are the leading class of biopharmaceuticals in terms of numbers approved for therapeutic purposes. Antigen‐binding fragments (Fab) are also used as biotherapeutics and used widely in research applications. The dominant expression systems for full‐length antibodies are mammalian cell‐based, whereas for Fab molecules the preference has been an expression in bacterial systems. However, advances in CHO and downstream technologies make mammalian systems an equally viable option for small‐ and large‐scale Fab production. Using a panel of full‐length IgG antibodies and their corresponding Fab pair with different antigen specificities, we investigated the impact of the IgG and Fab molecule format on production from Chinese hamster ovary (CHO) cells and assessed the cellular capability to process and produce these formats. The full‐length antibody format resulted in the recovery of fewer mini‐pools posttransfection when compared to the corresponding Fab fragment format that could be interpreted as indicative of a greater overall burden on cells. Antibody‐producing cell pools that did recover were subsequently able to achieve higher volumetric protein yields (mg/L) and specific productivity than the corresponding Fab pools. Importantly, when the actual molecules produced per cell of a given format was considered (as opposed to mass), CHO cells produced a greater number of Fab molecules per cell than obtained with the corresponding IgG, suggesting that cells were more efficient at making the smaller Fab molecule. Analysis of cell pools showed that gene copy number was not correlated to the subsequent protein production. The amount of mRNA correlated with secreted Fab production but not IgG, whereby posttranscriptional processes act to limit antibody production. In summary, we provide the first comparative description of how full‐length IgG and Fab antibody formats impact on the outcomes of a cell line construction process and identify potential limitations in their production that could be targeted for engineering increases in the efficiency in the manufacture of these recombinant antibody formats

Adult-Onset Obesity Reveals Prenatal Programming of Glucose-Insulin Sensitivity in Male Sheep Nutrient Restricted during Late Gestation

BACKGROUND: Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restriction during early or late gestation on glucose tolerance and insulin sensitivity in the adult offspring when lean and obese. METHODS/PRINCIPAL FINDINGS: Pregnant sheep received adequate (1.0M; CE, n = 6) or energy restricted (0.7M) diet during early (1-65 days; LEE, n = 6) or late (65-128 days; LEL, n = 7) gestation (term approximately 147 days). Subsequent offspring remained on pasture until 1.5 years when all received glucose and insulin tolerance tests (GTT & ITT) and body composition determination by dual energy x-ray absorptiometry (DXA). All animals were then exposed to an obesogenic environment for 6-7 months and all protocols repeated. Prenatal dietary treatment had no effect on birth weight or on metabolic endpoints when animals were 'lean' (1.5 years). Obesity revealed generalised metabolic 'inflexibility' and insulin resistance; characterised by blunted excursions of plasma NEFA and increased insulin(AUC) (from 133 to 341 [s.e.d. 26] ng.ml(-1).120 mins) during a GTT, respectively. For LEL vs. CE, the peak in plasma insulin when obese was greater (7.8 vs. 4.7 [s.e.d. 1.1] ng.ml(-1)) and was exacerbated by offspring sex (i.e. 9.8 vs. 4.4 [s.e.d. 1.16] ng.ml(-1); LEL male vs. CE male, respectively). Acquisition of obesity also significantly influenced the plasma lipid and protein profile to suggest, overall, greater net lipogenesis and reduced protein metabolism. CONCLUSIONS: This study indicates generalised metabolic dysfunction with adult-onset obesity which also exacerbates and 'reveals' programming of glucose-insulin sensitivity in male offspring prenatally exposed to maternal undernutrition during late gestation. Taken together, the data suggest that metabolic function appears little compromised in young prenatally 'programmed' animals so long as weight is adequately controlled. Nutritional excess in adulthood exacerbates any programmed phenotype, indicating greater vigilance over weight control is required for those individuals exposed to nutritional thrift during gestation

Direct Visualization by Cryo-EM of the Mycobacterial Capsular Layer: A Labile Structure Containing ESX-1-Secreted Proteins

The cell envelope of mycobacteria, a group of Gram positive bacteria, is composed of a plasma membrane and a Gram-negative-like outer membrane containing mycolic acids. In addition, the surface of the mycobacteria is coated with an ill-characterized layer of extractable, non-covalently linked glycans, lipids and proteins, collectively known as the capsule, whose occurrence is a matter of debate. By using plunge freezing cryo-electron microscopy technique, we were able to show that pathogenic mycobacteria produce a thick capsule, only present when the cells were grown under unperturbed conditions and easily removed by mild detergents. This detergent-labile capsule layer contains arabinomannan, α-glucan and oligomannosyl-capped glycolipids. Further immunogenic and proteomic analyses revealed that Mycobacterium marinum capsule contains high amounts of proteins that are secreted via the ESX-1 pathway. Finally, cell infection experiments demonstrated the importance of the capsule for binding to cells and dampening of pro-inflammatory cytokine response. Together, these results show a direct visualization of the mycobacterial capsular layer as a labile structure that contains ESX-1-secreted proteins