It is not clear how to effectively recruit healthy research volunteers.
We developed an electronic health record (EHR)-based algorithm to identify healthy subjects, who were randomly assigned to ...receive an invitation to join a research registry via the EHR's patient portal, letters, or phone calls. A follow-up survey assessed contact preferences.
The EHR algorithm accurately identified 858 healthy subjects. Recruitment rates were low, but occurred more quickly via the EHR patient portal than letters or phone calls (2.7 vs. 19.3 or 10.4 d). Effort and costs per enrolled subject were lower for the EHR patient portal (3.0 vs. 17.3 or 13.6 h, $113 vs. $559 or $435). Most healthy subjects indicated a preference for contact via electronic methods.
Healthy subjects can be accurately identified from EHR data, and it is faster and more cost-effective to recruit healthy research volunteers using an EHR patient portal.
The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of ...pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset-accessible through the Beat AML data viewer (Vizome)-that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML.
Elevated levels of C-reactive protein (CRP) and D-dimer (DD) have been associated with the presence and progression of various forms of atherosclerotic disease, particularly coronary heart disease. ...We hypothesize that there is a relationship between elevated levels of baseline CRP and DD and progression of peripheral arterial disease (PAD) in patients with symptomatic PAD. The current study is a prospective evaluation of this hypothesis.
Between 1996 and 2003, 384 subjects were enrolled in a National Institutes of Health-sponsored blinded, prospective trial evaluating the effects of multiple atherosclerotic risk factors on progression of symptomatic PAD. Baseline levels of CRP and D-dimer were obtained in 332 subjects. Subjects were followed every 6 months with clinical history and exam, ankle-brachial pressure index (ABI), and carotid artery duplex scanning (CDS). The primary study end point was a composite of ABI progression, CDS progression, stroke, myocardial infarction, amputation, and death from cardiovascular disease. Secondary end points included each of the components of the primary end point. The relationship between time to the various endpoints and baseline CRP and DD levels was examined by life-table analysis and Cox proportional hazards analysis.
Adequate baseline samples for CRP and DD were available in 332 subjects (mean age, 67 years; 57.8% men) with mean follow-up of 38.4 months (range, 1 to 99 months). Mean baseline levels (± SD) for CRP were 0.8 ± 1.14 (range, 0.03 to 13.0), and mean DD levels were 227.4 ± 303.3 (range, 1.9 to 2744.8). Progression, as defined by the primary end point, occurred in 48.5% of subjects. Subjects with elevated CRP (highest tertile) were no more likely to have any of the progression end points than those with the lowest values (lowest tertile) (P = NS, log-rank test, for all comparisons). By univariate analysis, subjects with elevated DD (highest tertile) were significantly more likely to die from any cause compared with subjects with the lowest DD values (lowest tertile) (P = .03, log-rank test). They were, however, no more likely to reach any of the other progression end points, including the primary end point (P = NS, log-rank test for all other comparisons). Multivariate analysis showed that DD level was a significant independent variable associated with occurrence of myocardial infarction (hazard ratio, 2.3; P = .02).
In subjects with symptomatic PAD, elevated baseline DD, a marker of thrombotic activity, was significantly associated with the occurrence of myocardial infarction. This study did not confirm a relationship between progression of PAD and baseline DD or CRP during the first 3 years. Baseline DD and CRP do not provide useful risk stratification in patients at high risk for progression of symptomatic PAD. Future studies should evaluate serial levels of these markers to assess their utility in predicting progression of symptomatic PAD.
BACKGROUND
Alternate tapping speed is widely used as a measure of bradykinesia in Parkinson's disease (PD). Tapping speed in normal control subjects and factors that might influence tapping speed ...have not been systematically examined.
OBJECTIVE
To examine the effects of age, hand dominance, and gender on tapping speed in normal control subjects and to compare the effects of practice on tapping speed in normal and PD control subjects.
METHODS
Tapping speed for three sequential trials in the dominant and nondominant hand was examined in 100 normal control subjects and 60 subjects with PD. The effect of hourly practice over 26 hours (19 trials) was investigated in 14 normal and 24 PD subjects.
RESULTS
The speed with which normal subjects alternately tapped two counters was negatively correlated with age, was greater in the dominant hand, was not related to gender, and improved with short‐term practice (three trials) and with continued practice over 26 hours. Parkinsonian subjects, in general, tapped more slowly than normal control subjects and more slowly in the more affected arm. Parkinsonian subjects benefited from short‐term practice as much as normal control subjects but, unlike normal control subjects, did not improve with continued practice over 26 hours.
CONCLUSIONS
Alternate tapping speed is influenced by age, hand dominance, Parkinson's disease, and practice. Subjects with PD do not benefit as much from continued practice as do normal subjects, suggesting some limitation or impairment of procedural (motor) learning in PD.
Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or “long COVID”), but they are difficult to integrate because of heterogeneous methods and the ...lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies.
The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19.
We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies.
Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID.
U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411.
We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new ...cohort using infant pulmonary function tests.
To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor.
A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo.
The primary outcome was FEF
at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF
and FEF
obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (
= 113) had the following FEFs at 3 months of age compared with those randomized to placebo (
= 109) as measured by FEF
(200.7 vs. 188.7 ml/s; adjusted 95% confidence interval CI for difference, -3.33 to 35.64;
= 0.10), FEF
(436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30;
= 0.02), and FEF
(387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34;
= 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968).
Although the primary outcome of FEF
was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF
and FEF
were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF
and FEF
) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).
Purpose: There have been few studies of the natural history of peripheral arterial disease (PAD), and none have used serial noninvasive laboratory examinations for the objective quantification of ...disease progression. The relationship between the site of initial symptoms of PAD (lower-extremity disease LED vs cerebrovascular disease CVD) and the site of subsequent symptomatic progression (LED vs CVD vs coronary heart disease CHD) has not been examined. Methods: This is a long-term, blinded prospective clinical research study of the relationship of PAD progression to multiple clinical, laboratory, and noninvasive vascular laboratory parameters. Patients with symptomatic LED, CVD, or both underwent comprehensive risk-factor assessment and were seen every 6 months for follow-up examinations. In addition to history and physical examination, all subjects underwent serial noninvasive lower-extremity and carotid artery testing. The relationship between the initial symptomatic site(s) and subsequent progression was examined by means of multivariate proportional hazards analysis, which was adjusted for age, diabetes mellitus, hypertension, smoking, cholesterol, homocysteine level, lowest initial ankle/brachial index (ABI), worst carotid stenosis, ABI progression, and carotid stenosis progression, because each of these factors was significantly associated with one or more aspects of progression. Results: There were 397 study subjects (mean age, 66 years; 38% women) with a mean follow-up period of 48.5 months. LED was initially present in 88% of subjects and CVD in 37% of subjects (both were present in 25% of subjects). There were 78 deaths, 47 (60%) of which were caused by cardiovascular disease (18% mortality rate after 5 years by means of life table). Progression of disease as documented by means of vascular laboratory findings occurred in 90% of subjects by means of life table after 5 years (ABI progression, 31%; carotid stenosis progression, 40%). Symptomatic clinical progression of disease occurred in 52% of subjects by means of life table after 5 years (LED progression, 22%; CVD progression, 23%; CHD progression, 31%). By means of multivariate analysis, no significant relationship was found between the site of initial symptoms of PAD and the site(s) of subsequent symptomatic clinical progression (LED vs CVD vs CHD; P = not significant for all hazard ratios). Conclusion: Patients with symptomatic PAD experience symptoms of ongoing LED, CVD, and CHD with a frequency that is not influenced by the site(s) of their original symptoms. The hypothesis that lesions and resulting symptoms of systemic atherosclerosis occur at various anatomic sites as a matter of random chance should be tested with other studies. (J Vasc Surg 2002;35:38-47.)
Clinical integrated data repositories (IDRs) are poised to become a foundational element of biomedical and translational research by providing the coordinated data sources necessary to conduct ...retrospective analytic research and to identify and recruit prospective research subjects. The Clinical and Translational Science Award (CTSA) consortium's Informatics IDR Group conducted a survey of 2010 consortium members to evaluate recent trends in IDR implementation and use to support research between 2008 and 2010. A web-based survey based in part on a prior 2008 survey was developed and deployed to 46 national CTSA centers. A total of 35 separate organizations completed the survey (74%), representing 28 CTSAs and the National Institutes of Health Clinical Center. Survey results suggest that individual organizations are progressing in their approaches to the development, management, and use of IDRs as a means to support a broad array of research. We describe the major trends and emerging practices below.
Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences ...and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.
We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical
, 886,193
, and 113,627
.
We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.
We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.
Abstract Despite strong anti-smoking efforts, at least 12% of American women cannot quit smoking when pregnant resulting in > 450,000 smoke-exposed infants born yearly. Smoking during pregnancy is ...the largest preventable cause of childhood respiratory illness including wheezing and asthma. Recent studies have shown a protective effect of vitamin C supplementation on the lung function of offspring exposed to in utero smoke in a non-human primate model and an initial human trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to evaluate pulmonary function at 3 months of age in infants delivered to pregnant smokers randomized to 500 mg/day of vitamin C versus placebo during pregnancy. Secondary aims evaluate the incidence of wheezing through 12 months and pulmonary function testing at 12 months of age. Women are randomized between 13 and 23 weeks gestation from clinical sites in Portland, Oregon at Oregon Health & Science University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from randomization to delivery. Monthly contact with participants and monitoring of medical records is performed to document medication adherence, changes in smoking and medical history, and adverse events. Pulmonary function testing of offspring occurs at 3 and 12 months of age and incidence of wheezing and respiratory illness through 12 months is captured via at least quarterly questionnaires. Ancillary studies are investigating the impact of vitamin C on placental blood flow and DNA methylation.
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