Patient care in complex Sociotechnological ecosystems and learning health systems.

The learning health system (LHS) model was proposed to provide real-time, bi-directional flow of learning using data captured in health information technology systems to deliver rapid learning in healthcare delivery. As highlighted by the landmark National Academy of Medicine report "Crossing the Quality Chasm," the U.S. healthcare delivery industry represents complex adaptive systems, and there is an urgent need to develop innovative methods to identify efficient team structures by harnessing real-world care delivery data found in the electronic health record (EHR). We offer a discussion surrounding the complexities of team communication and how solutions may be guided by theories such as the Multiteam System (MTS) framework and the Multitheoretical Multilevel Framework of Communication Networks. To advance healthcare delivery science and promote LHSs, our team has been building a new line of research using EHR data to study MTS in the complex real world of cancer care delivery. We are developing new network metrics to study MTSs and will be analyzing the impact of EHR communication network structures on patient outcomes. As this research leads to patient care delivery interventions/tools, healthcare leaders and healthcare professionals can effectively use health IT data to implement the most evidence-based collaboration approaches in order to achieve the optimal LHS and patient outcomes.

Effectiveness of implementing evidence-based approaches to promote physical activity in a Midwestern micropolitan area using a quasi-experimental hybrid type I study design.

BACKGROUND: Much evidence-based physical activity (PA) interventions have been tested and implemented in urban contexts. However, studies that adapt, implement, and evaluate the effectiveness of these interventions in micropolitan rural contexts are needed. The study aimed to evaluate the effectiveness of the Active Ottumwa intervention to promote PA in a micropolitan community. METHODS: Between 2013 - 2019, we implemented Active Ottumwa in a micropolitan setting, and subsequently implemented and evaluated its effectiveness using a Hybrid Type I design. In this paper, we describe the intervention's effectiveness in promoting PA. We collected PA data over 24 months from a cohort of community residents using accelerometers and PA data from two cross-sectional community surveys administered in 2013 and 2018, using the Global Physical Activity Questionnaire. RESULTS: From the cohort, we found significant change in PA over 24 months (P = 0.03) corresponding to a 45-min daily decrease in sedentary activity, a daily increase of 35-min in light PA and 9 min in moderate-to-vigorous PA. There was a statistically significant (P = 0.01) increasing trend at the population-level in the moderate-to-vigorous composition of 7 min between the two cross-sectional assessments (95% CI: 0.1%-1.34%). CONCLUSIONS: The study demonstrates that the adapted evidence-based PA interventions in a micropolitan context is effective.

Comparing multiple infection control measures in a nursing home setting: a simulation study.

OBJECTIVE: Compare the effectiveness of multiple mitigation measures designed to protect nursing home residents from infectious disease outbreaks. DESIGN: Agent-based simulation study. SETTING: Simulation environment of a small nursing home. METHODS: We collected temporally detailed and spatially fine-grained location information from nursing home healthcare workers (HCWs) using sensor motes. We used these data to power an agent-based simulation of a COVID-19 outbreak using realistic time-varying estimates of infectivity and diagnostic sensitivity. Under varying community prevalence and transmissibility, we compared the mitigating effects of (i) regular screening and isolation, (ii) inter-resident contact restrictions, (iii) reduced HCW presenteeism, and (iv) modified HCW scheduling. RESULTS: Across all configurations tested, screening every other day and isolating positive cases decreased the attack rate by an average of 27% to 0.501 on average, while contact restrictions decreased the attack rate by an average of 35%, resulting in an attack rate of only 0.240, approximately half that of screening/isolation. Combining both interventions impressively produced an attack rate of only 0.029. Halving the observed presenteeism rate led to an 18% decrease in the attack rate, but if combined with screening every 6 days, the effect of reducing presenteeism was negligible. Altering work schedules had negligible effects on the attack rate. CONCLUSIONS: Universal contact restrictions are highly effective for protecting vulnerable nursing home residents, yet adversely affect physical and mental health. In high transmission and/or high community prevalence situations, restricting inter-resident contact to groups of 4 was effective and made highly effective when paired with weekly testing.

The "dirty work" of last responders: Occupational stigma risk and protective factors.

Last responders constitute an occupational category that includes all those who are involved in the postmortem care of deceased persons and their families. The work of last responders is often considered "dirty work" and, as a result, stigmatized. Last responders are aware of this stigma, and stigma consciousness has been associated with negative health outcomes. Despite the wide acknowledgment of stigma among last responders, specific risk, or protective factors for experiencing stigma have not been investigated. This paper aims to identify determinants of stigma among last responders in the United States. The data for this study were obtained from a national cross-sectional survey of last responders. The survey included a measure of stigma and multiple sociodemographic characteristics. A hurdle model was used to assess the association between the characteristics of last responders and their perceived stigma. Respondents were predominantly male (55.1%), White non-Hispanic (90.2%), and employed full-time (96%). Seventy-seven percent reported having experienced at least one form of occupation-related stigma. There was no significant association between the experience of stigma and any socio-demographic variables. The experience of stigma is nearly ubiquitous among last responders->75% of last responders in the sample experienced at least one form of stigma. Another aspect of its ubiquitous nature is the lack of evidence that stigma was experienced differentially across sex, race/ethnicity, employment type, and length of years as a last responder. Interventions are needed to decrease stigma among last responders and to support last responders in managing the consequences of the stigma they experience.

The Association Between State Characteristics and Latinx People's Treated Hypertension in Established and New Latinx Destination States: A Multilevel Analysis.

This study sought to quantify the contributions of state-level factors including income inequality, state's legislature political control, and Medicaid expansion in new and established Latinx destination states on Latinx individuals' treated hypertension. Mixed-effects logistic regression analyses were conducted to analyze 2017 Behavioral Risk Factor Surveillance System data from 7524 Latinx adults nested within 39 states. Overall, 70% reported being pharmacologically treated for hypertension, and 66% resided in established destination states. Compared with Latinx people in established destination states, Latinx people in new destinations had lower odds of having treated hypertension (odds ratio [OR] = 0.72, 95% CI = 0.54-0.95). Within established Latinx destinations, the odds of treated hypertension were lower in states where legislatures expanded Medicaid than in states that did not expand Medicaid (OR = 0.84, 95% CI = 0.79-0.89). However, after controlling for the effects of individual-level factors, this association was no longer statistically significant. In new Latinx destination states, Medicaid expansion, legislatures' political control, and income inequality were not associated with treated hypertension. The study results highlight the importance of considering both individual- and state-level factors, as the interplay of such factors could hinder the successful implementation of cardiovascular risk reduction interventions.

Enterococcus contamination of infant foods and implications for exposure to foodborne pathogens in peri-urban neighbourhoods of Kisumu, Kenya.

We collected infant food samples from 714 households in Kisumu, Kenya, and estimated the prevalence and concentration of Enterococcus, an indicator of food hygiene conditions. In a subset of 212 households, we quantified the change in concentration in stored food between a morning and afternoon feeding time. In addition, household socioeconomic characteristics and hygiene practices of the caregivers were documented. The prevalence of Enterococcus in infant foods was 50% (95% confidence interval: 46.1 - 53.4), and the mean log10 colony-forming units (CFUs) was 1.1 (SD + 1.4). No risk factors were significantly associated with the prevalence and concentration of Enterococcus in infant foods. The mean log10 CFU of Enterococcus concentration was 0.47 in the morning and 0.73 in the afternoon foods with a 0.64 log10 mean increase in matched samples during storage. Although no factors were statistically associated with the prevalence and the concentration of Enterococcus in infant foods, household flooring type was significantly associated with an increase in concentration during storage, with finished floors leading to 1.5 times higher odds of concentration increase compared to unfinished floors. Our study revealed high prevalence but low concentration of Enterococcus in infant food in low-income Kisumu households, although concentrations increased during storage implying potential increases in risk of exposure to foodborne pathogens over a day. Further studies aiming at investigating contamination of infant foods with pathogenic organisms and identifying effective mitigation measures are required to ensure infant food safety.

Protocol for the PATHOME study: a cohort study on urban societal development and the ecology of enteric disease transmission among infants, domestic animals and the environment.

INTRODUCTION: Global morbidity from enteric infections and diarrhoea remains high in children in low-income and middle-income countries, despite significant investment over recent decades in health systems and water and sanitation infrastructure. Other types of societal development may be required to reduce disease burden. Ecological research on the influence of household and neighbourhood societal development on pathogen transmission dynamics between humans, animals and the environment could identify more effective strategies for preventing enteric infections. METHODS AND ANALYSIS: The 'enteric pathome'-that is, the communities of viral, bacterial and parasitic pathogens transmitted from human and animal faeces through the environment is taxonomically complex in high burden settings. This integrated cohort-exposure assessment study leverages natural socioeconomic spectrums of development to study how pathome complexity is influenced by household and neighbourhood infrastructure and hygiene conditions. We are enrolling under 12-month-old children in low-income and middle-income neighbourhoods of two Kenyan cities (Nairobi and Kisumu) into a 'short-cohort' study involving repeat testing of child faeces for enteric pathogens. A mid-study exposure assessment documenting infrastructural, behavioural, spatial, climate, environmental and zoonotic factors characterises pathogen exposure pathways in household and neighbourhood settings. These data will be used to inform and validate statistical and agent-based models (ABM) that identify individual or combined intervention strategies for reducing multipathogen transmission between humans, animals and environment in urban Kenya. ETHICS AND DISSEMINATION: The protocols for human subjects' research were approved by Institutional Review Boards at the University of Iowa (ID-202004606) and AMREF Health Africa (ID-ESRC P887/2020), and a national permit was obtained from the Kenya National Commission for Science Technology and Innovation (ID# P/21/8441). The study was registered on Clinicaltrials.gov (Identifier: NCT05322655) and is in pre-results stage. Protocols for research on animals were approved by the University of Iowa Animal Care and Use Committee (ID 0042302).

Predicting use of a gait-stabilizing device using a Wii Balance Board.

Gait-stabilizing devices (GSDs) are effective at preventing falls, but people are often reluctant to use them until after experiencing a fall. Inexpensive, convenient, and effective methods for predicting which patients need GSDs could help improve adoption. The purpose of this study was to determine if a Wii Balance Board (WBB) can be used to determine whether or not patients use a GSD. We prospectively recruited participants ages 70-100, some who used GSDs and some who did not. Participants first answered questions from the Modified Vulnerable Elders Survey, and then completed a grip-strength test using a handgrip dynamometer. Finally, they were asked to complete a series of four 30-second balance tests on a WBB in random order: (1) eyes open, feet apart; (2) eyes open, feet together; (3) eyes closed, feet apart; and (4) eyes closed, feet together. The four-test series was repeated a second time in the same random order. The resulting data, represented as 25 features extracted from the questionnaires and the grip test, and data from the eight balance tests, were used to predict a subject's GSD use using generalized functional linear models based on the Bernoulli distribution. 268 participants were consented; 62 were missing data elements and were removed from analysis; 109 were not GSD users and 97 were GSD users. The use of velocity and acceleration information from the WBB improved upon predictions based solely on grip strength, demographic, and survey variables. The WBB is a convenient, inexpensive, and easy-to-use device that can be used to recommend whether or not patients should be using a GSD.

Comparison of Different Antibiotics and the Risk for Community-Associated Clostridioides difficile Infection: A Case-Control Study.

Background: Antibiotics are the greatest risk factor for Clostridioides difficile infection (CDI). Risk for CDI varies across antibiotic types and classes. Optimal prescribing and stewardship recommendations require comparisons of risk across antibiotics. However, many prior studies rely on aggregated antibiotic categories or are underpowered to detect significant differences across antibiotic types. Using a large database of real-world data, we evaluate community-associated CDI risk across individual antibiotic types. Methods: We conducted a matched case-control study using a large database of insurance claims capturing longitudinal health care encounters and medications. Case patients with community-associated CDI were matched to 5 control patients by age, sex, and enrollment period. Antibiotics prescribed within 30 days before the CDI diagnosis along with other risk factors, including comorbidities, health care exposures, and gastric acid suppression were considered. Conditional logistic regression and a Bayesian analysis were used to compare risk across individual antibiotics. A sensitivity analysis of antibiotic exposure windows between 30 and 180 days was conducted. Results: We identified 159 404 cases and 797 020 controls. Antibiotics with the greatest risk for CDI included clindamycin and later-generation cephalosporins, and those with the lowest risk included minocycline and doxycycline. We were able to differentiate and order individual antibiotics in terms of their relative level of associated risk for CDI. Risk estimates varied considerably with different exposure windows considered. Conclusions: We found wide variation in CDI risk within and between classes of antibiotics. These findings ordering the level of associated risk across antibiotics can help inform tradeoffs in antibiotic prescribing decisions and stewardship efforts.

Ignored and distressed: a cross-sectional study of the impact of COVID-19 on last responders.

BACKGROUND: Last responders constitute an occupational category that includes all those that are involved in the postmortem care of deceased persons and their families. Last responders are exposed to several categories of work-related stressors that affect their health and well-being. COVID-19 exacerbated these stressors. Research to understand the consequences of COVID-19 on the health and wellbeing of last responders is nascent. This study aimed to assess COVID-19 related stress, coping and wellbeing among last responders in the United States. METHODS: We conducted a national cross-sectional survey of last responders in July through September of 2020. The survey measured wellbeing, stress, coping, and stigma; COVID-19 experiences, and socio-demographics. A ridge regression model was fit for the outcome variables. RESULTS: Analysis was conducted on 366 respondents from 43 states. Respondents were male (55.4%), age 50 + (57.4%), and White non-Hispanic (90.3%); 54% reported moderate-high stress and 41% endorsed mild-severe anxiety. Seventy-seven percent had experienced at least one form of stigma related to their occupation. Variables associated with higher perceived stress and anxiety included gender (female), shorter length of employment, perceiving a higher impact from COVID-19 on everyday life, and increased perceived stigma. CONCLUSIONS: Last responders are a critical part of the health care system. Throughout this pandemic, last responders have been frequently ignored and not prioritized for protection and support. Interventions to support last responders cope with stress, and to decrease anxiety are urgently needed. There is also a critical need to challenge community stigma towards last responders.

Pathogen and human NDPK-proteins promote AML cell survival via monocyte NLRP3-inflammasome activation.

A history of infection has been linked with increased risk of acute myeloid leukaemia (AML) and related myelodysplastic syndromes (MDS). Furthermore, AML and MDS patients suffer frequent infections because of disease-related impaired immunity. However, the role of infections in the development and progression of AML and MDS remains poorly understood. We and others previously demonstrated that the human nucleoside diphosphate kinase (NDPK) NM23-H1 protein promotes AML blast cell survival by inducing secretion of IL-1ß from accessory cells. NDPKs are an evolutionary highly conserved protein family and pathogenic bacteria secrete NDPKs that regulate virulence and host-pathogen interactions. Here, we demonstrate the presence of IgM antibodies against a broad range of pathogen NDPKs and more selective IgG antibody activity against pathogen NDPKs in the blood of AML patients and normal donors, demonstrating that in vivo exposure to NDPKs likely occurs. We also show that pathogen derived NDPK-proteins faithfully mimic the catalytically independent pro-survival activity of NM23-H1 against primary AML cells. Flow cytometry identified that pathogen and human NDPKs selectively bind to monocytes in peripheral blood. We therefore used vitamin D3 differentiated monocytes from wild type and genetically modified THP1 cells as a model to demonstrate that NDPK-mediated IL-1ß secretion by monocytes is NLRP3-inflammasome and caspase 1 dependent, but independent of TLR4 signaling. Monocyte stimulation by NDPKs also resulted in activation of NF-κB and IRF pathways but did not include the formation of pyroptosomes or result in pyroptotic cell death which are pivotal features of canonical NLRP3 inflammasome activation. In the context of the growing importance of the NLRP3 inflammasome and IL-1ß in AML and MDS, our findings now implicate pathogen NDPKs in the pathogenesis of these diseases.

Students supporting students: evaluating the impact of the COVID-19 pandemic on resident assistant mental health.

OBJECTIVE: To examine the impact of the novel coronavirus SARS-CoV2 (COVID-19) pandemic on Residents Assistants (RA) at a public university in the Midwest. PARTICIPANTS: Sixty-seven RAs that had been offered an RA position for the '20-'21 academic year. METHODS: An online cross-sectional survey measuring socio-demographics, stress, and well-being was fielded. MANCOVA models evaluated the impact of COVID-19 on well-being of Current RAs and compared to the non-current RA groups. RESULTS: Sixty-seven RAs provided valid data. Overall, 47% of RAs had moderate-severe anxiety and 86.3% had moderate-high level of stress. Current RAs perceiving a great impact of COVID on life had significantly more stress, anxiety, burnout, and secondary traumatic stress than those who did not. RAs who started then quit experienced significantly higher secondary trauma compared to Current RAs. CONCLUSIONS: Further research is needed to better understand the experiences and of RAs and to develop policies and programs to support RAs.

Identifying the Social Determinants of Treated Hypertension in New and Established Latino Destination States.

Little is known about the influence of social and environmental contexts on Latino hypertension-related disparities. This study examined the influence of social determinants of cardiovascular health on medically treated hypertension, contrasting established vs. new Latino destination states. Logistic regression models were fitted to analyze 2017 Behavioral Risk Factors Surveillance Survey data from 8,999 Latinos. Overall, 70.4% indicated having treated hypertension. History of diabetes (OR = 2.60) and access to healthcare (OR = 2.38) were associated with treated hypertension, regardless of destination state. In established destinations, Latinos who graduated high school (OR = 1.19) or attended college (OR = 1.32) had higher odds of treated hypertension; whereas those who completed college were less likely to have treated hypertension (OR = 0.80). In contrast, in both new and non-destination states, the odds of treated hypertension were consistently lower across levels of educational attainment. Results highlight the need for cardiovascular-risk reduction interventions to incorporate the social and environmental context in the development process.

Evidence of within-facility patient-patient Clostridiodes difficile infection spread across diverse settings.

Previous studies have suggested that a hospital patient's risk of developing healthcare facility-onset (HCFO) Clostridioides difficile infections (CDIs) increases with the number of concurrent spatially proximate patients with CDI, termed CDI pressure. However, these studies were performed either in a single institution or in a single state with a very coarse measure of concurrence. We conducted a retrospective case-control study involving over 17.5 million inpatient visits across 700 hospitals in eight US states. We built a weighted, directed network connecting overlapping inpatient visits to measure facility-level CDI pressure. We then matched HCFO-CDIs with non-CDI controls on facility, comorbidities and demographics and performed a conditional logistic regression to determine the odds of developing HCFO-CDI given the number of coincident patient visits with CDI. On average, cases' visits coincided with 9.2 CDI cases, which for an individual with an average length of stay corresponded to an estimated 17.7% (95% CI 12.9-22.7%) increase in the odds of acquiring HCFO-CDI compared to an inpatient visit without concurrent CDI cases or fully isolated from both direct and indirect risks from concurrent CDI cases. These results suggest that, either directly or indirectly, hospital patients with CDI lead to CDIs in non-infected patients with temporally overlapping visits.

Applying network analysis to assess the development and sustainability of multi-sector coalitions.

BACKGROUND: Accountable Communities of Health (ACH) models have been popularized through Center for Medicare and Medicaid Innovation (CMMI) grants, including the State Innovation Model (SIM), to encourage the development of community-based coalitions across medical, public health, and social service delivery systems. These models enhance care coordination for patients and are better equipped to address Social Determinants of Health (SDH) needs. METHODS: Network data was collected from participating organizations in seven ACH sites established across Iowa. The application of network analysis quantitatively characterized the relational context of the interorganizational, cross-sector networks which are foundational to achieving the ACH goal of systematic, comprehensive care. Our analysis primarily used logistic network regression modeling (LNRM) to identify network structures and characteristics of organizations that facilitate or impede sustainable connections. RESULTS: Our findings suggest that the ACH was effective at stimulating sustainable connections across sectors and disparate positions of centrality in the network. Factors associated with sustainable connections between organizations included the strength of relationships and the type of collaboration, namely data sharing and resource sharing. Leadership roles designated by the ACH structure were associated with stimulating connections during the grant, but not with sustainment. Network measures of density and transitivity, which peaked during the grant period (compared to pre- and post-grant networks), further implied possible attrition of the ACH intervention effects without incentive to maintain collaborations. CONCLUSIONS: Multi-sector care coordination networks were established, but our findings suggest depreciation of ACH intervention momentum and structure without incentive to maintain collaborations beyond the three-year duration of the grant. Sustainability could be bolstered and ACH goals actualized with reliable long-term funding.

Environmental and behavioural exposure pathways associated with diarrhoea and enteric pathogen detection in 5-month-old, periurban Kenyan infants: a cross-sectional study.

OBJECTIVES: The aim of this study was to test whether household environmental hygiene and behavioural conditions moderated associations between diarrhoea and enteric pathogen detection in infants 5 months of age in Kenya and pathogen sources, including latrine access, domestic animal co-habitation and public food sources. DESIGN: Cross-sectional study utilising enrolment survey data of households participating in the Safe Start cluster-randomised controlled trial . SETTING: Kisumu, Kenya. PARTICIPANTS: A total of 898 caregivers with 5-month (22 week ± 1 week) aged infants were enrolled in the study and completed the enrolment survey. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes were (1) caregiver-reported 7-day diarrhoea prevalence and (2) count of types of enteric viruses, bacteria and parasites in infant stool. Exposures and effect modifiers included water access and treatment, cohabitation with domestic animals, sanitation access, handwashing practices, supplemental feeding, access to refrigeration and flooring. RESULTS: Reported handwashing after handling animals (adjusted odds ratio (aOR)=0.20; 95% CI=0.06 to 0.50) and before eating (aOR=0.44; 95% CI=0.26 to 0.73) were strongly associated with lower risk of caregiver-reported diarrhoea, while cohabitation with animals (aOR=1.54; 95% CI=1.01 to 2.34) living in a household with vinyl-covered dirt floors (aOR=0.60; 95% CI=0.45 to 0.87) were strongly associated with pathogen codetection in infants. Caregiver handwashing after child (p=0.02) or self-defecation (p=0.03) moderated the relationship between shared sanitation access and infant exposure to pathogens, specifically private latrine access was protective against pathogen exposure of infants in households, where caregivers washed hands after defecation. In the absence of handwashing, access to private sanitation posed no benefits over shared latrines for protecting infants from exposure. CONCLUSION: Our evidence highlights eliminating animal cohabitation and improving flooring, postdefecation and food-related handwashing, and safety and use of cow milk sources as interventions to prevent enteric pathogen exposure of young infants in Kenya. TRIAL REGISTRATION NUMBER: NCT03468114.

Network-Informed Constrained Divisive Pooled Testing Assignments.

Frequent universal testing in a finite population is an effective approach to preventing large infectious disease outbreaks. Yet when the target group has many constituents, this strategy can be cost prohibitive. One approach to alleviate the resource burden is to group multiple individual tests into one unit in order to determine if further tests at the individual level are necessary. This approach, referred to as a group testing or pooled testing, has received much attention in finding the minimum cost pooling strategy. Existing approaches, however, assume either independence or very simple dependence structures between individuals. This assumption ignores the fact that in the context of infectious diseases there is an underlying transmission network that connects individuals. We develop a constrained divisive hierarchical clustering algorithm that assigns individuals to pools based on the contact patterns between individuals. In a simulation study based on real networks, we show the benefits of using our proposed approach compared to random assignments even when the network is imperfectly measured and there is a high degree of missingness in the data.

Risk for Asymptomatic Household Transmission of Clostridioides difficile Infection Associated with Recently Hospitalized Family Members.

We evaluated whether hospitalized patients without diagnosed Clostridioides difficile infection (CDI) increased the risk for CDI among their family members after discharge. We used 2001-2017 US insurance claims data to compare monthly CDI incidence between persons in households with and without a family member hospitalized in the previous 60 days. CDI incidence among insurance enrollees exposed to a recently hospitalized family member was 73% greater than enrollees not exposed, and incidence increased with length of hospitalization among family members. We identified a dose-response relationship between total days of within-household hospitalization and CDI incidence rate ratio. Compared with persons whose family members were hospitalized <1 day, the incidence rate ratio increased from 1.30 (95% CI 1.19-1.41) for 1-3 days of hospitalization to 2.45 (95% CI 1.66-3.60) for >30 days of hospitalization. Asymptomatic C. difficile carriers discharged from hospitals could be a major source of community-associated CDI cases.

Leveraging network structure to improve pooled testing efficiency.

Screening is a powerful tool for infection control, allowing for infectious individuals, whether they be symptomatic or asymptomatic, to be identified and isolated. The resource burden of regular and comprehensive screening can often be prohibitive, however. One such measure to address this is pooled testing, whereby groups of individuals are each given a composite test; should a group receive a positive diagnostic test result, those comprising the group are then tested individually. Infectious disease is spread through a transmission network, and this paper shows how assigning individuals to pools based on this underlying network can improve the efficiency of the pooled testing strategy, thereby reducing the resource burden. We designed a simulated annealing algorithm to improve the pooled testing efficiency as measured by the ratio of the expected number of correct classifications to the expected number of tests performed. We then evaluated our approach using an agent-based model designed to simulate the spread of SARS-CoV-2 in a school setting. Our results suggest that our approach can decrease the number of tests required to regularly screen the student body, and that these reductions are quite robust to assigning pools based on partially observed or noisy versions of the network.

Mild Cognitive Impairment as an Early Landmark in Huntington's Disease.

As one of the clinical triad in Huntington's disease (HD), cognitive impairment has not been widely accepted as a disease stage indicator in HD literature. This work aims to study cognitive impairment thoroughly for prodromal HD individuals with the data from a 12-year observational study to determine whether Mild Cognitive Impairment (MCI) in HD gene-mutation carriers is a defensible indicator of early disease. Prodromal HD gene-mutation carriers evaluated annually at one of 32 worldwide sites from September 2002 to April 2014 were evaluated for MCI in six cognitive domains. Linear mixed-effects models were used to determine age-, education-, and retest-adjusted cut-off values in cognitive assessment for MCI, and then the concurrent and predictive validity of MCI was assessed. Accelerated failure time (AFT) models were used to determine the timing of MCI (single-, two-, and multiple-domain), and dementia, which was defined as MCI plus functional loss. Seven hundred and sixty-eight prodromal HD participants had completed all six cognitive tasks, had MRI, and underwent longitudinal assessments. Over half (i.e., 54%) of the participants had MCI at study entry, and half of these had single-domain MCI. Compared to participants with intact cognitive performances, prodromal HD with MCI had higher genetic burden, worsened motor impairment, greater brain atrophy, and a higher likelihood of estimated HD onset. Prospective longitudinal study of those without MCI at baseline showed that 48% had MCI in subsequent visits and data visualization suggested that single-domain MCI, two-domain MCI, and dementia represent appropriate cognitive impairment staging for HD gene-mutation carriers. Findings suggest that MCI represents an early landmark of HD and may be a sensitive enrichment variable or endpoint for prodromal clinical trials of disease modifying therapeutics.