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In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.
Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.
Clinical trials face many challenges with meeting projected enrollment and retention goals. A study’s recruitment materials and messaging convey necessary key information and therefore serve as a critical first impression with potential participants. Yet study teams often lack the resources and skills needed to develop engaging, culturally tailored, and professional-looking recruitment materials. To address this gap, the Recruitment Innovation Center recently developed a Recruitment & Retention Materials Content and Design Toolkit, which offers research teams guidance, actionable tips, resources, and customizable templates for creating trial-specific study materials. This paper seeks to describe the creation and contents of this new toolkit.
New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.
Racially and ethnically minoritized populations have been historically excluded and underrepresented in research. This paper will describe best practices in multicultural and multilingual awareness-raising strategies used by the Recruitment Innovation Center to increase minoritized enrollment into clinical trials. The Passive Immunity Trial for Our Nation will be used as a primary example to highlight real-world application of these methods to raise awareness, engage community partners, and recruit diverse study participants.
The Recruitment Innovation Center (RIC) has created a toolkit of novel strategies to engage potential participants in response to recruitment and retention challenges associated with COVID-19 studies. The toolkit contains pragmatic, generalizable resources to help research teams increase awareness of clinical trials and opportunities to participate; produce culturally sensitive and engaging recruitment materials; improve consent and return of results processes; and enhance recruitment of individuals from populations disproportionately impacted by COVID-19. This resource, the “RIC COVID-19 Recruitment and Retention Toolkit,” is available free online. We describe the toolkit and the community feedback used to author and curate this resource.
As clinical trials were rapidly initiated in response to the COVID-19 pandemic, Data and Safety Monitoring Boards (DSMBs) faced unique challenges overseeing trials of therapies never tested in a disease not yet characterized. Traditionally, individual DSMBs do not interact or have the benefit of seeing data from other accruing trials for an aggregated analysis to meaningfully interpret safety signals of similar therapeutics. In response, we developed a compliant DSMB Coordination (DSMBc) framework to allow the DSMB from one study investigating the use of SARS-CoV-2 convalescent plasma to treat COVID-19 to review data from similar ongoing studies for the purpose of safety monitoring.
The DSMBc process included engagement of DSMB chairs and board members, execution of contractual agreements, secure data acquisition, generation of harmonized reports utilizing statistical graphics, and secure report sharing with DSMB members. Detailed process maps, a secure portal for managing DSMB reports, and templates for data sharing and confidentiality agreements were developed.
Four trials participated. Data from one trial were successfully harmonized with that of an ongoing trial. Harmonized reports allowing for visualization and drill down into the data were presented to the ongoing trial’s DSMB. While DSMB deliberations are confidential, the Chair confirmed successful review of the harmonized report.
It is feasible to coordinate DSMB reviews of multiple independent studies of a similar therapeutic in similar patient cohorts. The materials presented mitigate challenges to DSMBc and will help expand these initiatives so DSMBs may make more informed decisions with all available information.
Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.
Laboratory studies were conducted to determine the relative sorption, mobility, and degradation rates of triclopyr and 2,4-D on two surface soils and two subsoils from the rice-producing areas of Arkansas. Triclopyr sorption was slightly greater than 2,4-D sorption. However, mobility of the herbicides on a given soil did not differ. Sorption of both herbicides was greatest and mobility lowest on a subsoil with the lowest pH. Triclopyr degradation rates were lower than 2,4-D degradation rates in a dark incubator. The average half life was 138 d for triclopyr and 21 d for 2,4-D. High soil moisture content (0 versus 100 kPa water tension) increased the rate of 2,4-D degradation. Triclopyr degraded more rapidly at 30 C than at 15 C. The dissipation rates of both herbicides were lowest on the soil on which sorption was greatest.
The volatilization, photolysis, microbial degradation, and field persistence of imazethapyr were studied using formulated and 14C-labeled imazethapyr. Volatilization losses from soil were less than 2%. Photodecomposition losses of up to 8% occurred from soil and up to 52% from a glass slide with no soil. Significantly greater photodecomposition occurred with chain-labeled than ring-labeled 14C-imazethapyr. The amount of 14CO2 evolution from soil treated with either ring- or chain-labeled 14C-imazethapyr was not significantly different. The total 14CO2 evolved from the soils ranged from 2.4 to 3.6% of the total 14C-imazethapyr applied to the soil. However, degradation of imazethapyr from the same soils, as determined by high-pressure liquid chromatography, indicated that 62 to 82% of the applied 14C-imazethapyr had been degraded. The degradation rate increased as soil moisture was increased from −100 to −33 kPa. Imazethapyr was more persistent in soil with the higher clay and organic matter content.
Epidemiological evidence regarding the association between carbohydrate intake, glycaemic load (GL) and glycaemic index (GI) and risk of ovarian cancer has been mixed. Little is known about their impact on ovarian cancer risk in African-American women. Associations between carbohydrate quantity and quality and ovarian cancer risk were investigated among 406 cases and 609 controls using data from the African American Cancer Epidemiology Study (AACES). AACES is an ongoing population-based case–control study of ovarian cancer in African-Americans in the USA. Cases were identified through rapid case ascertainment and age- and site-matched controls were identified by random-digit dialling. Dietary information over the year preceding diagnosis or the reference date was obtained using a FFQ. Multivariable logistic regression models were used to estimate odds ratios and 95 % CI adjusted for covariates. The OR comparing the highest quartile of total carbohydrate intake and total sugar intake v. the lowest quartile were 1·57 (95 % CI 1·08, 2·28; Ptrend=0·03) and 1·61 (95 % CI 1·12, 2·30; Ptrend<0·01), respectively. A suggestion of an inverse association was found for fibre intake. Higher GL was positively associated with the risk of ovarian cancer (OR 1·18 for each 10 units/4184 kJ (1000 kcal); 95 % CI 1·04, 1·33). No associations were observed for starch or GI. Our findings suggest that high intake of total sugars and GL are associated with greater risk of ovarian cancer in African-American women.
This paper summarises current research on the mental health status of older African-Americans with a specific focus on late-life depression, one of the most common forms of mental disorder among older persons. Social gerontologists have brought to the forefront the need to consider the impact of historical eras, cohort location, and lifecourse development when studying various dimensions of the ageing process. Unfortunately, this type of theorising is still in its infancy, and has not been widely applied to the general population and all dimensions of health, let alone investigations into the mental health status of older African-Americans. Virtually none of the empirical studies we reviewed adequately address the historical, biographical, or structural factors related to the mental health status of older African-Americans. We suggest that to understand contemporary manifestations of racial presumptions, there must be an appreciation of the historical antecedents. African-Americans live with the corrosive effects of a legacy of slavery that presumed black inferiority. The identification of salient factors of risk and resilience among this population is critical to developing effective intervention and mental health maintenance programmes. By emphasising the socio-historical influences on the mental health of older African-Americans, we can develop a greater understanding of this population's mental health needs; thus paving the way for improved mental health services and a reduction in mental health disparities.
Our previous studies revealed abnormalities on structural MRI (sMRI) in small groups of children exposed to alcohol prenatally. Microcephaly, disproportionately reduced basal ganglia volume, and abnormalities of the cerebellar vermis and corpus callosum were demonstrated. The present study used sMRI to examine in detail the regional pattern of brain hypoplasia resulting from prenatal exposure to alcohol using a higher resolution imaging protocol and larger sample sizes than reported previously. Fourteen participants (mean 11.4 years; eight females, six males) with fetal alcohol syndrome (FAS) and 12 participants (mean 14.8 years; four females, eight males) with prenatal exposure to alcohol (PEA) but without the facial features of FAS were compared to a group of 41 control participants (mean 12.8 years, 20 females, 21 males). Findings of significant microcephaly and disproportionately reduced basal ganglia volumes in the FAS group were confirmed. Novel findings were that in FAS participants, white matter volumes were more affected than gray matter volumes in the cerebrum, and parietal lobes were more affected than temporal and occipital lobes. Among subcortical structures, in contrast to the disproportionate effects on caudate nucleus, the hippocampus was relatively preserved in FAS participants. Differences between the PEA group and controls were generally non-significant; however, among a few of the structures most affected in FAS participants, there was some evidence for volume reduction in PEA participants as well, specifically in basal ganglia and the parietal lobe. There were no group differences in cerebral volume asymmetries. Severe prenatal alcohol exposure appears to produce a specific pattern of brain hypoplasia.
Focal lesions leading to psychosis are relatively rare. For example, of 1821 men with focal brain lesions due to trauma, only 21 showed psychotic symptoms (six with paranoid psychosis and 15 with schizophrenia-like psychosis) (Hillbom, 1951). Lesions in many areas have been implicated in the causation of psychosis; however, there are no areas that, when lesioned, reliably produce psychotic symptoms. This chapter reviews the location of lesions that have been associated with psychosis and factors that contribute to the expression of psychosis. Lesions associated with psychosis found in epilepsy, stroke, demyelinating syndromes, neoplasms, trauma, and focally degenerative diseases are described. Conditions associated with psychosis and the brain regions commonly involved are summarized in Table 15.1.
Psychosis has many possible definitions; the definition employed in this chapter is 'the inability to distinguish reality from fantasy with impaired reality testing and the creation of a new reality’ (Kaplan and Saddock, 1995) manifested by the presence of delusions or hallucinations. Other definitions of psychosis include impairment of personal and social functioning and thought disorder, but these qualities extend beyond the core syndrome and would include many patients with uncomplicated neurological disorders. Delusions will be defined as false beliefs based on incorrect inferences about external reality and firmly held in spite of evidence to the contrary (Cummings, 1995b). Hallucinations will be denned as sensory perceptions occurring without appropriate external stimulation of the relative sensory organ, and are only manifestations of psychosis if the perceiver believes them to be real. They will be included in this discussion only if the hallucinations are psychotic manifestations.
The Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS) is currently processing and immobilizing the radioactive high level waste sludge at SRS into a durable borosilicate glass for final geological disposal. The DWPF has recently finished processing the first radioactive sludge batch, and is ready for the second batch ofradioactive sludge. The second batch is primarily sludge from Tank 42. Before processing this batch in the DWPF, the DWPF process flowsheet has to be demonstrated with a sample of Tank 42 sludge to ensure that an acceptable melter feed and glass can be made. This demonstration was recently completed in the Shielded Cells Facility at SRS. An earlier paper in these proceedings described the sludge composition and processes necessary for producing an acceptable melter feed . This paper describes the preparation and characterization of the glass from that demonstration. Results substantiate that Tank 42 sludge after mixing with the proper amount of glass forming frit (Frit 200) can be processed to make an acceptable glass.
Emergency medical technicians (EMTs) find that the death of patients in their care is stressful.
Random sample of certified EMTs in one state (Levels I–IV).
A blinded, self-administered survey was sent to a random sample of 2,500 EMTs. Demographic data obtained were: level of training; hours worked each month; population of area served; age; gender; number of deaths per year; training for coping prehospital deaths; and availability of protocols and on-line medical advice for out-of-hospital deaths. A five-point, Likert scale was used to rate the frequency of perceived stress experienced by EMTs in specific situations and the routine practice for notification of survivors. Univariable analysis was performed using Spearman's Rank correlation, Kruskal-Wallis test, and Mann-Whitney U-test. Multivariable correlations were performed using forward and backward step-wise logistic regression analysis. A significance level of 0.05 was used throughout.
There were 654 respondents with a mean age of 35.5±8.3 yr; 83% were men. Their highest level of training was: 4% EMT-I, 43% EMT-II, 18% EMT-III, 33% EMT-IV. They saw an average of 9.6 deaths/year and spent an average of 20±17 minutes with survivors. 62 % found treatment of a patient that was dying or died in their care was commonly a stressful experience. Factors that made notification of the family about the prehospital death emotionally difficult included: fewer hours worked/month; working in a smaller community; lower level of EMT training; female gender; and fewer deaths seen during the previous year. The same factors were associated with general emotional difficulty in treatment of a patient who died during prehospital care. Online [direct] medical direction by physicians was common (73%), but did not lessen the difficulty of notification. It did reduce the emotional difficulty for specific clinical situations. Written protocols for not attempting resuscitation were common (66%), but only 44% had protocols for termination of resuscitation. Resuscitation of the clearly dead for the benefit of the family (10%) or for the EMT (5%) was practiced infrequently. Most (67%) respondents had some formal training in dealing with death and the dying patient. Such training did not correlate with less difficulty in notification of survivors or in coping with the deaths of patients in their care.
EMTs perceive they have emotional difficulty when prehospital deaths occur and survivors must be notified. Less experience and a lower level of EMT training correlate with more difficulty in coping with patient death. Protocols and on-line [direct] medical control can provide support for the EMT in coping with out-of-hospital deaths. Most notification of survivors is handled by EMTs with formal training to cope with patients that are dying or who die during prehospital care.
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