Recommendations of Common Data Elements to Advance the Science of Selfâ Management of Chronic Conditions

PurposeCommon data elements (CDEs) are increasingly being used by researchers to promote data sharing across studies. The purposes of this article are to (a) describe the theoretical, conceptual, and definition issues in the development of a set of CDEs for research addressing selfâ management of chronic conditions; (b) propose an initial set of CDEs and their measures to advance the science of selfâ management; and (c) recommend implications for future research and dissemination.Design and MethodsBetween July 2014 and December 2015 the directors of the National Institute of Nursing Research (NINR)â funded P20 and P30 centers of excellence and NINR staff met in a series of telephone calls and a faceâ toâ face NINRâ sponsored meeting to select a set of recommended CDEs to be used in selfâ management research. A list of potential CDEs was developed from examination of common constructs in current selfâ management frameworks, as well as identification of variables frequently used in studies conducted in the centers of excellence.FindingsThe recommended CDEs include measures of three selfâ management processes: activation, selfâ regulation, and selfâ efficacy for managing chronic conditions, and one measure of a selfâ management outcome, global health.ConclusionsThe selfâ management of chronic conditions, which encompasses a considerable number of processes, behaviors, and outcomes across a broad range of chronic conditions, presents several challenges in the identification of a parsimonious set of CDEs. This initial list of recommended CDEs for use in selfâ management research is provisional in that it is expected that over time it will be refined. Comment and recommended revisions are sought from the research and practice communities.Clinical RelevanceThe use of CDEs can facilitate generalizability of research findings across diverse population and interventions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134268/1/jnu12233_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134268/2/jnu12233.pd

Biomarkers as Common Data Elements for Symptom and Selfâ Management Science

PurposeBiomarkers as common data elements (CDEs) are important for the characterization of biobehavioral symptoms given that once a biologic moderator or mediator is identified, biologically based strategies can be investigated for treatment efforts. Just as a symptom inventory reflects a symptom experience, a biomarker is an indicator of the symptom, though not the symptom per se. The purposes of this position paper are to (a) identify a â minimum setâ of biomarkers for consideration as CDEs in symptom and selfâ management science, specifically biochemical biomarkers; (b) evaluate the benefits and limitations of such a limited array of biomarkers with implications for symptom science; (c) propose a strategy for the collection of the endorsed minimum set of biologic samples to be employed as CDEs for symptom science; and (d) conceptualize this minimum set of biomarkers consistent with National Institute of Nursing Research (NINR) symptoms of fatigue, depression, cognition, pain, and sleep disturbance.Design and MethodsFrom May 2016 through January 2017, a working group consisting of a subset of the Directors of the NINR Centers of Excellence funded by P20 or P30 mechanisms and NINR staff met bimonthly via telephone to develop this position paper suggesting the addition of biomarkers as CDEs. The full group of Directors reviewed drafts, provided critiques and suggestions, recommended the minimum set of biomarkers, and approved the completed document. Best practices for selecting, identifying, and using biological CDEs as well as challenges to the use of biological CDEs for symptom and selfâ management science are described. Current platforms for sample outcome sharing are presented. Finally, biological CDEs for symptom and selfâ management science are proposed along with implications for future research and use of CDEs in these areas.FindingsThe recommended minimum set of biomarker CDEs include proâ and antiâ inflammatory cytokines, a hypothalamicâ pituitaryâ adrenal axis marker, cortisol, the neuropeptide brainâ derived neurotrophic factor, and DNA polymorphisms.ConclusionsIt is anticipated that this minimum set of biomarker CDEs will be refined as knowledge regarding biologic mechanisms underlying symptom and selfâ management science further develop. The incorporation of biological CDEs may provide insights into mechanisms of symptoms, effectiveness of proposed interventions, and applicability of chosen theoretical frameworks. Similarly, as for the previously suggested NINR CDEs for behavioral symptoms and selfâ management of chronic conditions, biological CDEs offer the potential for collaborative efforts that will strengthen symptom and selfâ management science.Clinical RelevanceThe use of biomarker CDEs in biobehavioral symptoms research will facilitate the reproducibility and generalizability of research findings and benefit symptom and selfâ management science.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143764/1/jnu12378.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143764/2/jnu12378_am.pd

Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera

The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.</p

Diagnosis and management of Silver–Russell syndrome: first international consensus statement

This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver–Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p