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Under enrollment of participants in clinical research is costly and delays study completion to impact public health. Given that research personnel make decisions about which strategies to pursue and participants are the recipients of these efforts, we surveyed research staff (n = 52) and participants (n = 4,144) affiliated with SPARK (Simons Foundation Powering Autism for Knowledge) – the largest study of autism in the U.S. – to understand their perceptions of effective recruitment strategies.
Methods:
In Study 1, research personnel were asked to report recruitment strategies that they tried for SPARK and to indicate which ones they would and would not repeat/recommend. In Study 2, SPARK participants were asked to indicate all the ways they heard about the study prior to enrollment and which one was most influential in their decisions to enroll.
Results:
Staff rated speaking with a SPARK-study-team member (36.5%), speaking with a medical provider (19.2%), word of mouth (11.5%), and a live TV news story (11.5%) as the most successful strategies. Participants most often heard about SPARK via social media (47.0%), speaking with a medical provider (23.1%), and an online search (20.1%). Research personnel’s and participants’ views on effective recruitment strategies often differed, with the exception of speaking with a medical provider.
Conclusion:
Results suggest that a combination of strategies is likely to be most effective in reaching diverse audiences. Findings have implications for the selection of strategies that meet a study’s specific needs, as well as recruitment-strategy “combinations” that may enhance the influence of outreach efforts.
Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
To evaluate the utility of selective reactive whole-genome sequencing (WGS) in aiding healthcare-associated cluster investigations.
Design:
Mixed-methods quality-improvement study.
Setting:
Thes study was conducted across 8 acute-care facilities in an integrated health system.
Methods:
We analyzed healthcare-associated coronavirus disease 2019 (COVID-19) clusters between May 2020 and July 2022 for which facility infection prevention and control (IPC) teams selectively requested reactive WGS to aid the epidemiologic investigation. WGS was performed with real-time results provided to IPC teams, including genetic relatedness of sequenced isolates. We conducted structured interviews with IPC teams on the informativeness of WGS for transmission investigation and prevention.
Results:
In total, 8 IPC teams requested WGS to aid the investigation of 17 COVID-19 clusters comprising 226 cases and 116 (51%) sequenced isolates. Of these, 16 (94%) clusters had at least 1 WGS-defined transmission event. IPC teams hypothesized transmission pathways in 14 (82%) of 17 clusters and used data visualizations to characterize these pathways in 11 clusters (65%). The teams reported that in 15 clusters (88%), WGS identified a transmission pathway; the WGS-defined pathway was not one that was predicted by epidemiologic investigation in 7 clusters (41%). WGS changed the understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in 8 clusters (47%) and altered infection prevention interventions in 8 clusters (47%).
Conclusions:
Selectively utilizing reactive WGS helped identify cryptic SARS-CoV-2 transmission pathways and frequently changed the understanding and response to SARS-CoV-2 outbreaks. Until WGS is widely adopted, a selective reactive WGS approach may be highly impactful in response to healthcare-associated cluster investigations.
SPARK launched in 2016 to build a US cohort of autistic individuals and their family members. Enrollment includes online consent to share data and optional consent to provide saliva for genomic analysis. SPARK’s recruitment strategies include social media and support of a nation-wide network of clinical sites. This study evaluates SPARK’s recruitment strategies to enroll a core study population.
Methods:
Individuals who joined between January 31, 2018, and May 29, 2019 were included in the analysis. Data include sociodemographic characteristics, clinical site referral, the website URL used to join, how the participant heard about SPARK, enrollment completion (online registration, study consents, and returning saliva sample), and completion of the baseline questionnaire. Logistic regressions were performed to evaluate the odds of core participant status (completing enrollment and baseline questionnaire) by recruitment strategy.
Results:
In total, 31,715 individuals joined during the study period, including 40% through a clinical site. Overall, 88% completed online registration, 46% returned saliva, and 38% were core participants. Those referred by a clinical site were almost twice as likely to be core participants. Those who directly visited the SPARK website or performed a Google search were more likely to be core participants than those who joined through social media.
Discussion:
Being a core participant may be associated with the “personal” connection and support provided by a clinical site and/or site staff, as well as greater motivation to seek research opportunities. Findings from this study underscore the value of adopting a multimodal recruitment approach that combines social media and a physical presence.
Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.
We analyzed efficacy of a centralized surveillance infection prevention (CSIP) program in a healthcare system on healthcare-associated infection (HAI) rates amid the coronavirus disease 2019 (COVID-19) pandemic. HAI rates were variable in CSIP and non-CSIP facilities. Central-line–associated bloodstream infection (CLABSI), C. difficile infection (CSI), and surgical-site infection (SSI) rates were negatively correlated with COVID-19 intensity in CSIP facilities.
To develop, implement, and evaluate the effectiveness of a unique centralized surveillance infection prevention (CSIP) program.
Design:
Observational quality improvement project.
Setting:
An integrated academic healthcare system.
Intervention:
The CSIP program comprises senior infection preventionists who are responsible for healthcare-associated infection (HAI) surveillance and reporting, allowing local infection preventionists (LIPs) a greater portion of their time to non-surveillance patient safety activities. Four CSIP team members accrued HAI responsibilities at 8 facilities.
Methods:
We evaluated the effectiveness of the CSIP program using 4 measures: recovery of LIP time, efficiency of surveillance activities by LIPs and CSIP staff, surveys characterizing LIP perception of their effectiveness in HAI reduction, and nursing leaders’ perception of LIP effectiveness.
Results:
The amount of time spent by LIP teams on HAI surveillance was highly variable, while CSIP time commitment and efficiency was steady. Post-CSIP implementation, 76.9% of LIPs agreed that they spend adequate time on inpatient units, compared to 15.4% pre-CSIP; LIPs also reported more time to allot to non-surveillance activities. Nursing leaders reported greater satisfaction with LIP involvement with HAI reduction practices.
Conclusion:
CSIP programs are a little-reported strategy to ease burden on LIPs with reallocation of HAI surveillance. The analyses presented here will aid health systems in anticipating the benefit of CSIP programs.
There is evidence that child maltreatment is associated with shorter telomere length in early life.
Aims
This study aims to examine if child maltreatment is associated with telomere length in middle- and older-age adults.
Method
This was a retrospective cohort study of 141 748 UK Biobank participants aged 37–73 years at recruitment. Leukocyte telomere length was measured with quantitative polymerase chain reaction, and log-transformed and scaled to have unit standard deviation. Child maltreatment was recalled by participants. Linear regression was used to analyse the association.
Results
After adjusting for sociodemographic characteristics, participants with three or more types of maltreatment presented with the shortest telomere lengths (β = −0.05, 95% CI −0.07 to −0.03; P < 0.0001), followed by those with two types of maltreatment (β = −0.02, 95% CI −0.04 to 0.00; P = 0.02), referent to those who had none. When adjusted for depression and post-traumatic stress disorder, the telomere lengths of participants with three or more types of maltreatment were still shorter (β = −0.04, 95% CI −0.07 to −0.02; P = 0.0008). The telomere lengths of those with one type of maltreatment were not significantly different from those who had none. When mutually adjusted, physical abuse (β = −0.05, 95% CI −0.07 to −0.03; P < 0.0001) and sexual abuse (β = −0.02, 95% CI −0.04 to 0.00; P = 0.02) were independently associated with shorter telomere length.
Conclusions
Our findings showed that child maltreatment is associated with shorter telomere length in middle- and older-aged adults, independent of sociodemographic and mental health factors.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Pulsatile tinnitus can be a symptom of vascular pathology. However, many of these pathologies present as incidental findings on scanning for unrelated symptoms. This study investigated whether the pathologies attributed to pulsatile tinnitus could instead be considered incidental findings.
Methods
This retrospective study evaluated imaging results of 272 pulsatile tinnitus cases for clinically relevant pathologies, and examined correlations between the site of symptoms and the imaging findings.
Results
Of 272 patients, 238 (88 per cent) had normal scans, 17 (6 per cent) had clinically insignificant incidental findings, and 18 (7 per cent) had findings requiring further investigation or intervention; regarding these latter 18 patients, findings for 8 patients (42 per cent) did not correlate with the symptomatic side. The rates of intracranial aneurysm and arteriovenous malformation in the pulsatile tinnitus group were comparable to those in normal populations.
Conclusion
The comparable rates of vascular abnormalities within the symptomatic pulsatile tinnitus group, plus clinically relevant findings contralateral to symptoms, suggest that vascular pathologies could be incidental findings rather than causes of pulsatile tinnitus. Evaluation is recommended of the effectiveness of the new National Institute for Health and Care Excellence guidelines for pulsatile tinnitus investigation.
Cognitive theories of depression contend that biased cognitive information processing plays a causal role in the development of depression. Extensive research shows that deeper processing of negative and/or shallower processing of positive self-descriptors (i.e., negative and positive self-schemas) predicts current and future depression in adults and children. However, the neural correlates of the development of self-referent encoding are poorly understood. We examined children's self-referential processing using the self-referent encoding task (SRET) collected from 74 children at ages 6, 9, and 12; around age 10, these children also contributed structural magnetic resonance imaging data. From age 6 to age 12, both positive and negative self-referential processing showed mean-level growth, with positive self-schemas increasing relatively faster than negative ones. Further, voxel-based morphometry showed that slower growth in positive self-schemas was associated with lower regional gray matter volume (GMV) in ventrolateral prefrontal cortex (vlPFC). Our results suggest that smaller regional GMV within vlPFC, a critical region for regulatory control in affective processing and emotion development, may have implications for the development of depressogenic self-referential processing in mid-to-late childhood.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
Uterine fibroids or leiomyomas are the most common benign gynaecological tumours; up to 25–30% of women may be diagnosed with fibroids during their lifetime [1]. Women with uterine fibroids may be asymptomatic, or they may present with menstrual symptoms such as menorrhagia and dysmenorrhoea, pressure symptoms, infertility, recurrent miscarriage or complications during pregnancy like red degeneration.
We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations.
Methods
Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression.
Results
We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05).
Conclusions
Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.
OBJECTIVES/GOALS: African-Americans have a 3-fold higher risk of end-stage kidney disease (ESKD) compared to Whites due in part to APOL1 risk alleles. Whether resistant hypertension (RH) magnifies the risk of ESKD among African Americans beyond APOL1 is not known. We examined the interaction between RH and race on ESKD risk and the independent effect of RH beyond APOL1. METHODS/STUDY POPULATION: We designed a retrospective cohort of 240,038 veterans with HTN, enrolled in the Million Veteran Program with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2. The primary exposure was incident RH (time-varying). The primary outcome was incident ESKD during a 13.5 year follow up: 2004-2017. Secondary outcomes were myocardial infarction (MI), stroke, and death. Incident RH was defined as failure to achieve outpatient blood pressure (BP) <140/90 mmHg with 3 antihypertensive drugs, including a thiazide, or use of 4 or more drugs. Poisson models were used to estimate incidence rates and test additive interaction with race and APOL1 genotype. Multivariable Cox models (with Fine-Gray competing-risks models as sensitivity analyses) were used to examine independent effects. RESULTS/ANTICIPATED RESULTS: The cohort comprised 235,046 veterans; median age was 60 years; 21% were African-American and 6% were women, with 23,010 incident RH cases observed over a median follow-up time of 10.2 years [interquartile range, 5.6-12.6]. Patients with RH had higher incidence rates [per 1000 person-years] of ESKD (4.5 vs. 1.3), myocardial infarction (6.5 vs. 3.0), stroke (16.4 vs. 7.6) and death (12.0 vs. 6.9) than non-resistant hypertension (NRH). African-Americans with RH had a 2.6-fold higher risk of ESKD compared to African-Americans with NRH; 3-fold the risk of Whites with RH, and 9.6-fold the risk of Whites with NRH [p-interaction<.001]. Among African-Americans, RH was associated with a 2.2-fold (95%CI, 1.86-2.58) higher risk of incident ESKD in models adjusted for APOL1 genotype and in the subset of African-Americans with no APOL1 risk alleles, RH was associated with an adjusted 2.75-fold (95% CI: 2.00-3.50) higher risk of incident ESKD. DISCUSSION/SIGNIFICANCE OF IMPACT: RH was independently associated with a higher risk of ESKD and cardiovascular outcomes, especially among African-Americans. This elevated risk is independent of APOL1 genotype. Interventions that achieve BP targets among patients with RH could curtail the incidence of ESKD and cardiovascular outcomes in this high-risk population. CONFLICT OF INTEREST DESCRIPTION: None.
Understanding the clinical risk factors for COVID-19 disease severity and outcomes requires a combination of data from electronic health records and patient reports. To facilitate the collection of patient-reported data, as well as accelerate and standardize the collection of data about host factors, we have constructed a COVID-19 survey. This survey is freely available to the scientific community to send electronically for patients to complete online. This patient survey is designed to be comprehensive, yet not overly burdensome, to gather data useful for a range of clinical investigations, and to accommodate a wide variety of implementation settings including at a COVID-19 testing site, at home during infection or after recovery, and/or for individuals while they are hospitalized. A widely adopted standardized survey that can be implemented online with minimal resources can serve as a critical tool for combining and comparing data across studies to improve our understanding of COVID-19 disease.
The turbulent boundary layer developing under a turbulence-laden free stream is numerically investigated using the temporal boundary layer framework. This study focuses on the interaction between the fully turbulent boundary layer and decaying free-stream turbulence. Previous experiments and simulations of this physical problem have considered a spatially evolving boundary layer beset by free-stream turbulence. The state of the boundary layer at any given downstream position in fact reflects the accumulated history of the co-evolution of boundary layer and free-stream turbulence. The central aim of the present work is to isolate the effect of local free-stream disturbances existing at the same time as the ‘downstream’ boundary layer. The temporal framework used here helps expose when and how disturbances directly above the boundary layer actively impart change upon it. The bulk of our simulations were completed by seeding the free stream above boundary layers that were ‘pre-grown’ to a desired thickness with homogeneous isotropic turbulence from a precursor simulation. Moreover, this strategy allowed us to test various combinations of the turbulence intensity and large-eddy length scale of the free-stream turbulence with respect to the corresponding scales of the boundary layer. The relative large-eddy turnover time scale between the free-stream turbulence and the boundary layer emerges as an important parameter in predicting if the free-stream turbulence and boundary layer interaction will be ‘strong’ or ‘weak’ before the free-stream turbulence eventually fades to a negligible level. If the large-eddy turnover time scale of the free-stream turbulence is much smaller than that of the boundary layer, the interaction will be ‘weak’, as the free-stream disturbances will markedly decay before the boundary layer is able be altered significantly as a result of the free-stream disturbances. For a ‘strong’ interaction, the injected free-stream turbulence causes increased spreading of the boundary layer away from the wall, permitting large incursions of free-stream fluid deep within it.
Depression is a common mental disorder that substantially impairs a client's functioning. the aim of this study is to examine the predictive factors of quality of life (QOL) for depression from longitudinal perspectives. 237 outpatients with depression were recruited in the study. They were from a psychiatric outpatient clinic in northern Taiwan. All subjects were tested on the baseline and followed up twice during 3-year period. the average age of subjects was 47.1 years. Most subjects were female, married and lived with their spouses.Seventy subjects participated in both follow ups (T2 and T3). there were no significant differences on the demographic characteristics at T1 between the respondents (N = 70) and non-respondents (N = 167) except for gender. the subjects were tested on the WHOQOL-BREF-Taiwan version, occupational self assessment, mastery, social support and Center of Epidemiology Study-Depression Scale (CESD). the data were analyzed by mixed effect model using SAS computer program.The severity of depression could predict overall QOL, overall health and 13 items of QOL. the type of antidepressants had significant impact on the subjects’ QOL in 10 items. the occupational competence and sense of mastery predicted 13 items (50%) and 14 items (53.8%), respectively.In order to advance the treatment outcomes, the professionals should pay more attention on the enhancement of the sense of competence and mastery. We suggested that treatments should target at improving adaptive skills, lifestyle, and occupational competence.
Results of comprehensive particle image velocimetry measurements investigating the dynamics of turbulent jets in a rotating fluid are presented. It is observed that background system rotation induces a time-periodic formation–breakdown cycle of the jets. The flow dynamics associated with this process is studied in detail. It is found that the frequency of the cycle increases linearly with the background rotation rate. The data show that the onset of the breakdown phase and of the reformation phase of the cycle can be characterized in terms of a local Rossby number employing an internal velocity and a length scale of the jet. The critical values for this local Rossby number, for onset of breakdown and reformation, scale linearly with a global Rossby number based on the flow conditions at the source. The analysis of the experimental data suggests centrifugal instability as the potential origin of the formation–breakdown cycle.
With their long geological history and stable low-Mg calcite shells, Rhynchonelliform brachiopods are attractive sources of environmental data such as past seawater temperature (Buening and Spero, 1996; Auclair et al., 2003; Brand et al., 2003; Parkinson et al., 2005). Concerns about the influence of vital effects on the stable isotope composition of brachiopod shells (Popp et al., 1986), led to isotope analyses of different parts of brachiopod shells in order to identify those parts of the shell that are influenced by any vital effect and those parts that may be suitable recorders of seawater temperature via stable oxygen isotope composition (Carpenter and Lohmann, 1995; Parkinson et al., 2005). Such detailed studies demonstrated that the outer primary layer of acicularcalcite is isotopically light in both δ18O and δ13C while the secondary layer, composed of calcite fibres, is in oxygen-isotope equilibrium with ambient seawater(Fig. 1) (Parkinson et al., 2005).