Sometimes It Is Okay to Get Personal: Individualizing Targets in Critical Care.
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ABSTRACT:
SUBMITTER: Gershengorn HB
PROVIDER: S-EPMC7667904 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To develop glycaemic goal individualization algorithms and assess potential impact on a healthcare system and different segments of the population with diabetes.A cross-sectional observational study of patients with diabetes in a primary care network age > 18 years with an HbA1c measured between 1 January and 31 December 2011. We applied diabetes guidelines to create targeted algorithms 1 and 2, which assigned HbA1c goals based on age, duration of diabetes (< 15 years or < 10 years), diabetes complications and Charlson co-morbidity score (< 6 or < 4) [targeted algorithm 2 was designed to assign more patients a goal < 64 mmol/mol (8.0%) than targeted algorithm 1]. Each patient's HbA1c was compared with these targeted goals and to the 'standard' goal < 53 mmol/mol (7.0%). Agreement was tested using McNemar's test.Overall, 55.7% of 12 199 patients would be considered controlled under the 'standard' approach, 61.2% under targeted algorithm 1 and 67.5% under targeted algorithm 2. Targeted algorithm 1 reclassified 1213 (23.6%) patients considered uncontrolled under the standard approach to controlled, P < 0.001. Targeted algorithm 2 reclassified 1844 (35.2%) patients, P < 0.001. Compared with those controlled under the standard goal, there was no significant difference in the proportion of those controlled using targeted goals who had Medicaid, had less than a high school diploma or received primary care in a federally qualified health centre.Two automated targeted algorithms would reclassify one quarter to one third of patients from uncontrolled to controlled within a primary care network without differentially affecting vulnerable patient subgroups.
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Project description:Importance:Diabetes guidelines recommend considering specific factors, such as diabetes duration and life expectancy, to individualize treatment in older adults. These individualized glycemic targets inform decisions on whether to intensify or deintensify medication treatment plans. How older adults with diabetes perceive these factors used to individualize glycemic targets is unknown. Objectives:To examine how older adults perceive factors used in diabetes guidelines for individualizing glycemic targets. Design, Setting, and Participants:A cross-sectional national survey was conducted from December 13, 2018, to January 3, 2019, of a nationally representative, probability-based online survey panel (KnowledgePanel). A total of 1364 KnowledgePanel members who were 65 years or older and had type 2 diabetes were invited to participate in the survey; 836 (61.3%) responded, and 818 (60.0%) completed the survey. Main Outcomes and Measures:The study randomized participants to 2 vignettes: one about adding and the other about removing diabetes medications from treatment plans. Participants rated the importance of 7 factors (diabetes duration, established diabetes complications, other health conditions, life expectancy, risk of adverse effects, cost, and treatment effort) in these treatment decisions using binary (yes/no) responses and the best-worst scaling method to quantify the factors' relative importance. All participants then answered questions on how different levels of each factor were associated with aggressiveness of diabetes treatment. Results:The sample included 818 participants (mean [SD] age, 74.0 [6.8] years; 469 [53.7%] male; and 668 [67.7%] white). A total of 410 participants answered questions about adding medicine, whereas 408 participants answered questions about stopping medicine. Of the 7 factors to consider for adding a diabetes medication to the treatment plan, the number who deemed each factor important ranged from 197 (45.6%) to 263 (62.8%). In contrast, these same factors were considered important by only 29 (8.4%) to 146 (37.7%) of participants when deciding to stop use of a diabetes medication. In both decisions, participants perceived the risk of adverse effects as the most important factor (relative importance was 22.8 for adding a medicine and 25.0 for stopping a medicine on a ratio scale in which, for each decision, the relative importance of the 7 factors adds up to 100, with 0 indicating complete indifference and 100 complete priority). In contrast to current guideline recommendations, most participants believed that patients with longer disease duration (498 [60.1%]), more established complications (632 [75.6%]), and greater number of other health conditions (545 [67.5%]) should receive more aggressive diabetes treatment. Conclusions and Relevance:Many older adults do not place high importance on factors recommended by guidelines to individualize diabetes treatment, especially when deciding to stop use of diabetes medications. Moreover, when considering treatment aggressiveness, many older adults weighted several factors in the opposite direction than suggested by the guidelines. Individualizing diabetes care in older adults will require effective communication regarding the benefits and consequences of making changes to treatment plans.
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Project description:Nanoplastics with small particle size and high surface area/volume ratio make them easy to absorb environmental pollutants and affect their bioavailability. In this study, polystyrene nanoplastic beads (PS-NPBs) with a particle size of 100nm and sunscreen butyl methoxydibenzoylmethane (BMDBM) contained in personal care products were chosen as target pollutants to study their developmental toxicity and interactive effects on zebrafish embryo. The exposure period was 2-12 hours post fertilization (hpf). The BMDBM and PS-NPBs significantly upregulated the genes related to antioxidant enzymes and downregulated the gene expression of aromatase and DNA methyltransferases, but the influenced genes were not exactly the same, and the combined exposure reduced the adverse effects on the expression of all genes. With the help of single-cell RNA sequencing technology, the neural mid cells were identified as the target cells of both pollutants, and brain development, head development and notch signaling pathway were the functions they commonly altered. The key genes and functions that are specifically affected by BMDBM and/or PS-NPBs were identified. The BMDBM mainly affect the differentiation and fate of neurons in central nervous system through the regulation of her5, her6, her11, lfng, pax2a and fgfr4. The PS-NPBs regulated the expression of olig2, foxg1a, fzd8b, six3a, rx1, lhx2b, nkx2.1a and sfrp5 to alter nervous system development, retinal development, and stem cell differentiation. The phenotypic responses of zebrafish larvae at 120 hpf were tested, and significant inhibition of locomotor activity was found, indicating that early disrupting effect on central nervous system would have a sustained impact on the behavior of zebrafish.
2020-09-12 | GSE157816 | GEO
Project description:Small molecule drug discovery commonly ventures into previously unknown and unexplored target space. For such programs, an important role of medicinal chemistry is to generate molecules that enable the most reliable conclusions from a preclinical target validation/invalidation study. Multiple facets of chemistry that provide the most rigorous results for such an experiment are highlighted.
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| PRJEB19391 | ENA
Project description:Individualized strategies for managing renal anaemia with erythropoiesis-stimulating agents (ESAs) need to be advanced. Recent outcomes from clinical studies prompted a narrowing of the guideline-recommended haemoglobin target (11-12 g/dL) due to increased mortality and morbidity when targeting higher haemoglobin concentrations. Maintaining a narrow target is a clinical challenge, as haemoglobin concentration tends to fluctuate. The goal of individualized treatment is to achieve the haemoglobin target at the lowest ESA dose while avoiding significant fluctuations in haemoglobin concentrations and persistently low or high concentrations. This may require changes to the ESA dose and dosing frequency over the course of treatment.
| S-EPMC4421434 | biostudies-literature
Project description:BackgroundCritically ill patients with 2009 H1N1 influenza are often treated in intensive care units (ICUs), representing significant risk of nosocomial transmission to critical care clinicians and other patients. Despite a large body of literature and guidelines recommending infection control practices, numerous barriers have been identified in ICUs, leading to poor compliance to the use of personal protective equipment (PPE). The use of PPE among critical care clinicians has not been extensively evaluated, especially during the pandemic influenza. This study examined the knowledge, attitudes, and self-reported behaviors, and barriers to compliance with the use of PPE among ICU healthcare workers (HCWs) during the pandemic influenza.Methodology/principal findingsA survey instrument consisting of 36 questions was developed and mailed to all HCWs in 21 ICUs in 17 provinces in China. A total of 733 physicians, nurses, and other professionals were surveyed, and 650 (88.7%) were included in the analysis. Fifty-six percent of respondents reported having received training program of pandemic influenza before they cared for H1N1 patients, while 77% reported to have adequate knowledge of self and patient protection. Only 18% of respondents were able to correctly identify all components of PPE, and 55% reported high compliance (>80%) with PPE use during patient care. In multivariate analysis, vaccination for 2009 H1N1 influenza, positive attitudes towards PPE use, organizational factors such as availability of PPE in ICU, and patient information of influenza precautions, as well as reprimand for noncompliance by the supervisors were associated with high compliance, whereas negative attitudes towards PPE use and violation of PPE use were independent predictors of low compliance.Conclusion/significanceKnowledge and self-reported compliance to recommended PPE use among Chinese critical care clinicians is suboptimal. The perceived barriers should be addressed in order to close the significant gap between perception and knowledge or behavior.
| S-EPMC3434157 | biostudies-literature
Project description:BackgroundCommercial data brokers have amassed large collections of primary care patient data in proprietary databases. Our study objective was to critically analyze how entities involved in the collection and use of these records construct the value of these proprietary databases. We also discuss the implications of the collection and use of these databases.MethodsWe conducted a critical qualitative content analysis using publicly available documents describing the creation and use of proprietary databases containing Canadian primary care patient data. We identified relevant commercial data brokers, as well as entities involved in collecting data or in using data from these databases. We sampled documents associated with these entities that described any aspect of the collection, processing, and use of the proprietary databases. We extracted data from each document using a structured data tool. We conducted an interpretive thematic content analysis by inductively coding documents and the extracted data.ResultsWe analyzed 25 documents produced between 2013 and 2021. These documents were largely directed at the pharmaceutical industry, as well as shareholders, academics, and governments. The documents constructed the value of the proprietary databases by describing extensive, intimate, detailed patient-level data holdings. They provided examples of how the databases could be used by pharmaceutical companies for regulatory approval, marketing and understanding physician behaviour. The documents constructed the value of these data more broadly by claiming to improve health for patients, while also addressing risks to privacy. Some documents referred to the trade-offs between patient privacy and data utility, which suggests these considerations may be in tension.ConclusionDocuments in our analysis positioned the proprietary databases as socially legitimate and valuable, particularly to pharmaceutical companies. The databases, however, may pose risks to patient privacy and contribute to problematic drug promotion. Solutions include expanding public data repositories with appropriate governance and external regulatory oversight.
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Project description:In practice, critical care practitioners individualize treatments and goals of care for each patient in light of that patient's acute and chronic pathophysiology, as well as their beliefs and values. Yet critical care researchers routinely measure one endpoint for all patients during randomized clinical trials (RCTs), eschewing any such individualization. More recent methodology work has explored the possibility that enrollment criteria in RCTs can be individualized, as can data analysis plans. Here we propose that the specific endpoints of a RCT can be individualized-that is, different patients within a single RCT might have different secondary endpoints measured. If done rigorously and objectively, based on pre-randomization data, such individualization of endpoints may improve the bedside usefulness of information obtained during a RCT, while perhaps also improving the power and efficiency of any RCT. We discuss the theoretical underpinnings of this proposal in light of related innovations in RCT design such as sliding dichotomies. We discuss what a full elaboration of such individualization would require, and outline a pragmatic initial step towards the use of "individualized secondary endpoints" in a large RCT evaluating optimal enteral nutrition targets in the critically ill.
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Project description:With the rapid evolution of next-generation DNA sequencing technologies, the cost of sequencing a human genome has plummeted, and genomics has started to pervade health care across all stages of life - from preconception to adult medicine. Challenges to fully embracing genomics in a clinical setting remain, but some approaches are starting to overcome these barriers, such as community-driven data sharing to improve the accuracy and efficiency of applying genomics to patient care.
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