Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8). DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD. HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data. We identified genetic variants at apolipoprotein E (APOE), BIN1, PSEN1, and LINC00320 associated with AD. We observed rare non-coding variants in the promoter of TOMM40 distinct of APOE.

Association analysis of mitochondrial DNA heteroplasmic variants: Methods and application.

We rigorously assessed a comprehensive association testing framework for heteroplasmy, employing both simulated and real-world data. This framework employed a variant allele fraction (VAF) threshold and harnessed multiple gene-based tests for robust identification and association testing of heteroplasmy. Our simulation studies demonstrated that gene-based tests maintained an appropriate type I error rate at α = 0.001. Notably, when 5 % or more heteroplasmic variants within a target region were linked to an outcome, burden-extension tests (including the adaptive burden test, variable threshold burden test, and z-score weighting burden test) outperformed the sequence kernel association test (SKAT) and the original burden test. Applying this framework, we conducted association analyses on whole-blood derived heteroplasmy in 17,507 individuals of African and European ancestries (31 % of African Ancestry, mean age of 62, with 58 % women) with whole genome sequencing data. We performed both cohort- and ancestry-specific association analyses, followed by meta-analysis on both pooled samples and within each ancestry group. Our results suggest that mtDNA-encoded genes/regions are likely to exhibit varying rates in somatic aging, with the notably strong associations observed between heteroplasmy in the RNR1 and RNR2 genes (p < 0.001) and advance aging by the Original Burden test. In contrast, SKAT identified significant associations (p < 0.001) between diabetes and the aggregated effects of heteroplasmy in several protein-coding genes. Further research is warranted to validate these findings. In summary, our proposed statistical framework represents a valuable tool for facilitating association testing of heteroplasmy with disease traits in large human populations.

Sustainability of an Opt-Out Electronic-Health Record-Based Tobacco Treatment Consult Service at a Large Safety-Net Hospital: A 6-Year Analysis.

INTRODUCTION: Our safety-net hospital implemented a hospital-based tobacco treatment intervention in 2016. We previously showed the intervention, an "opt-out" Electronic Health Record (EHR)-based Best Practice Alert (BPA)+ order-set that triggers consultation to an inpatient Tobacco Treatment Consult (TTC) service for all patients who smoke, improves smoking abstinence. We now report on sustainability, 6 years after inception. AIMS AND METHODS: We analyzed data collected between July 2016-June 2022 of patients documented as "currently smoking" in the EHR. Across the 6 years, we used Pearson's correlation analysis to compare Adoption (clinician acceptance of the BPA+ order-set, thus generating consultation to the TTC service); Reach (number of consultations completed by the TTC service); and Effectiveness (receipt of pharmacotherapy orders between patients receiving and not receiving consultations). RESULTS: Among 39 558 adult admissions (July 2016-June 2022) with "currently smoking" status in the EHR for whom the BPA triggered, clinicians accepted the TTC order set on 50.4% (19 932/39 558), though acceptance varied across services (eg, Cardiology [71%] and Obstetrics-Gynecology 12%]). The TTC service consulted on 17% (6779/39 558) of patients due to staffing constraints. Consultations ordered (r = -0.28, p = .59) and completed (r = 0.45, p = .37) remained stable over 6-years. Compared to patients not receiving consultations, patients receiving consultations were more likely to receive pharmacotherapy orders overall (inpatient: 50.8% vs. 35.1%, p < .0001; at discharge: 27.1% vs. 10%, p < .0001) and in each year. CONCLUSIONS: The "opt-out" EHR-based TTC service is sustainable, though many did not receive consultations due to resource constraints. Health care systems should elevate the priority of hospital-based tobacco treatment programs to increase reach to underserved populations. IMPLICATIONS: Our study shows that opt-out approaches that utilize the EHR are a sustainable approach to providing evidence-based tobacco treatment to all hospitalized individuals who smoke, regardless of readiness to stop smoking and clinical condition.

Association analysis of mitochondrial DNA heteroplasmic variants: methods and application.

We rigorously assessed a comprehensive association testing framework for heteroplasmy, employing both simulated and real-world data. This framework employed a variant allele fraction (VAF) threshold and harnessed multiple gene-based tests for robust identification and association testing of heteroplasmy. Our simulation studies demonstrated that gene-based tests maintained an appropriate type I error rate at α=0.001. Notably, when 5% or more heteroplasmic variants within a target region were linked to an outcome, burden-extension tests (including the adaptive burden test, variable threshold burden test, and z-score weighting burden test) outperformed the sequence kernel association test (SKAT) and the original burden test. Applying this framework, we conducted association analyses on whole-blood derived heteroplasmy in 17,507 individuals of African and European ancestries (31% of African Ancestry, mean age of 62, with 58% women) with whole genome sequencing data. We performed both cohort- and ancestry-specific association analyses, followed by meta-analysis on both pooled samples and within each ancestry group. Our results suggest that mtDNA-encoded genes/regions are likely to exhibit varying rates in somatic aging, with the notably strong associations observed between heteroplasmy in the RNR1 and RNR2 genes (p<0.001) and advance aging by the Original Burden test. In contrast, SKAT identified significant associations (p<0.001) between diabetes and the aggregated effects of heteroplasmy in several protein-coding genes. Further research is warranted to validate these findings. In summary, our proposed statistical framework represents a valuable tool for facilitating association testing of heteroplasmy with disease traits in large human populations.

Association of Common and Rare Variants with Alzheimer's Disease in over 13,000 Diverse Individuals with Whole-Genome Sequencing from the Alzheimer's Disease Sequencing Project.

Alzheimer's Disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. Here, we investigated the association between AD and both common variants and aggregates of rare coding and noncoding variants in 13,371 individuals of diverse ancestry with whole genome sequence (WGS) data. Pooled-population analyses identified genetic variants in or near APOE, BIN1, and LINC00320 significantly associated with AD (p < 5×10-8). Population-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and noncoding variants in this region. Finally, we observed suggestive associations (p < 5×10-5) of aggregates of rare coding rare variants in ABCA7 among non-Hispanic Whites (p=5.4×10-6), and rare noncoding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p=7.2×10-8). Complementary pooled-population and population-specific analyses offered unique insights into the genetic architecture of AD.

A Longitudinal Study of Perceptions of the Massachusetts Menthol Ban and Its Impact on Smoking Behaviors among Marginalized Individuals.

Menthol cigarettes have had a profound adverse effect on public health. On 1 June 2020, Massachusetts became the first state to ban the sale of menthol cigarettes. We explored how perceptions of the ban and smoking behaviors changed over time among a group of 27 individuals who smoked menthol cigarettes at our safety-net hospital. In a convergent mixed methods study, we administered questionnaires and interviews simultaneously at two timepoints: 1 month pre-ban and 6 months post-ban. Pre-ban, we assessed perceptions of the ban and anticipated smoking behaviors after the ban. Post-ban, we assessed participants' actual smoking behaviors and elicited suggestions to avoid unintended consequences that might undermine intended policy effects. Several respondents perceived the Massachusetts ban as positive because it could promote smoking cessation, prevent youth initiation, and mitigate unfair targeting of socioeconomically disadvantaged populations. Others perceived the ban as an overreach of government policy, financially motivated, and unfairly targeting the Black community. Many continued to smoke menthol cigarettes obtained outside Massachusetts. Individuals suggested promoting tobacco treatment for people affected by the ban and a national ban to circumvent out-of-state purchasing of menthol cigarettes. Our findings suggest that in order to be most effective, healthcare systems must promote tobacco treatment and ensure that treatment is accessible to all individuals affected by the ban.

A Financial Incentives Program to Promote Smoking Cessation Among Recently Hospitalized Individuals: Feasibility and Acceptability Study.

BACKGROUND: Hospitalization is an opportunity to engage underserved individuals in tobacco treatment who may not otherwise have access to it. Tobacco treatment interventions that begin during hospitalization and continue for at least 1 postdischarge month are effective in promoting smoking cessation. However, there is low usage of postdischarge tobacco treatment services. Financial incentives for smoking cessation are an intervention in which participants receive incentives, such as cash payments or vouchers for goods, to encourage individuals to stop smoking or to reward individuals for maintaining abstinence. OBJECTIVE: We sought to determine the feasibility and acceptability of a novel postdischarge financial incentive intervention that uses a smartphone application paired to measurements of exhaled carbon monoxide (CO) concentration levels to promote smoking cessation in individuals who smoke cigarettes. METHODS: We collaborated with Vincere Health, Inc. to tailor their mobile application that uses facial recognition features, a portable breath test CO monitor, and smartphone technology to deliver financial incentives to a participant's digital wallet after the completion of each CO test. The program includes 3 racks. Track 1: Noncontingent incentives for conducting CO tests. Track 2: Combination of noncontingent and contingent incentives for CO levels <10 parts per million (ppm). Track 3: Contingent incentives only for CO levels <10 ppm. After obtaining informed consent, we pilot-tested the program from September to November 2020 with a convenience sample of 33 hospitalized individuals at Boston Medical Center, a large safety-net hospital in New England. Participants received text reminders to conduct CO tests twice daily for 30 days postdischarge. We collected data on engagement, CO levels, and incentives earned. We measured feasibility and acceptability quantitatively and qualitatively at 2 and 4 weeks. RESULTS: Seventy-six percent (25/33) completed the program and 61% (20/33) conducted at least 1 breath test each week. Seven patients had consecutive CO levels <10 ppm during the last 7 days of the program. Engagement with the financial incentive intervention as well as in-treatment abstinence was highest in Track 3 that delivered financial incentives contingent on CO levels <10 ppm. Participants reported high program satisfaction and that the intervention helped motivate smoking cessation. Participants suggested increasing program duration to at least 3 months and adding supplemental text messaging to increase motivation to stop smoking. CONCLUSIONS: Financial incentives paired to measurements of exhaled CO concentration levels is a novel smartphone-based tobacco cessation approach that is feasible and acceptable. Future studies should examine the efficacy of the intervention after it is refined to add a counseling or text-messaging component.

Cohort profile: the South African National Health Laboratory Service (NHLS) National HIV Cohort.

PURPOSE: South Africa's National Health Laboratory Service (NHLS) National HIV Cohort was established in 2015 to facilitate monitoring, evaluation and research on South Africa's National HIV Treatment Programme. In South Africa, 84.8% of people living with HIV know their HIV status; 70.7% who know their status are on ART; and 87.4% on ART are virologically suppressed. PARTICIPANTS: The NHLS National HIV Cohort includes the laboratory data of nearly all patients receiving HIV care in the public sector since April 2004. Patients are included in the cohort if they have received a CD4 count or HIV RNA viral load (VL) test. Using an anonymised unique patient identifier that we have developed and validated to linked test results, we observe patients prospectively through their laboratory results as they receive HIV care and treatment. Patients in HIV care are seen for laboratory monitoring every 6-12 months. Data collected include age, sex, facility location and test results for CD4 counts, VLs and laboratory tests used to screen for potential treatment complications. FINDINGS TO DATE: From April 2004 to April 2018, 63 million CD4 count and VL tests were conducted at 5483 facilities. 12.6 million unique patients had at least one CD4 count or VL, indicating they had accessed HIV care, and 7.1 million patients had a VL test indicating they had started antiretroviral therapy. The creation of NHLS National HIV Cohort has enabled longitudinal research on all lab-monitored patients in South Africa's national HIV programme, including analyses of (1) patient health at presentation; (2) care outcomes such as 'CD4 recovery', 'retention in care' and 'viral resuppression'; (3) patterns of transfer and re-entry into care; (4) facility-level variation in care outcomes; and (5) impacts of policies and guideline changes. FUTURE PLANS: Continuous updating of the cohort, integration with available clinical data, and expansion to include tuberculosis and other lab-monitored comorbidities.

Integrating Social Determinants of Health With Tobacco Treatment for Individuals With Opioid Use Disorder: Feasibility and Acceptability Study of Delivery Through Text Messaging.

BACKGROUND: Individuals with opioid use disorder (OUD) have a high prevalence of smoking and frequently experience unmet social determinants of health (SDOH), which may be barriers to smoking cessation. Hospitalization is an opportunity to encourage smoking cessation. Unfortunately, many clinicians do not provide tobacco treatment to support the maintenance of cessation achieved during hospitalization. Interventions are required to support these high-risk individuals after hospital discharge. OBJECTIVE: This study aimed to test the feasibility and acceptability of a 28-day SMS text messaging program tailored to individuals with OUD, which provides smoking cessation support and addresses unmet SDOH needs. METHODS: From July to December 2019, we enrolled 25 individuals who were hospitalized with tobacco dependence and OUD at our large safety net hospital. The SMS text messaging program was initiated during hospitalization and continued for 28 days. Participants were enrolled in either the ready to quit within 30 days or the not ready to quit within 30 days program based on their readiness to quit. Automated SMS text messages were sent twice daily for 4 weeks. The topics included health and cost benefits of quitting, both general and opioid specific (16 messages); managing mood and stress (8 messages); motivation, coping strategies, and encouragement (18 messages); addressing medication misconceptions (5 messages); links to resources to address substance use (2 messages providing links to the Massachusetts Substance Use Helpline and Boston Medical Center resources), tobacco dependence (1 message providing a link to the Massachusetts Quitline), and unmet SDOH needs (6 messages assessing SDOH needs with links to resources if unmet SDOH needs were identified). Questionnaires and interviews were conducted at baseline and at 2 and 4 weeks after enrollment. RESULTS: The participants were 56% (14/25) female, 36% (9/25) African American, 92% (23/25) unemployed, and 96% (24/25) Medicaid insured. Approximately 84% (21/25) activated the program, and none of the participants unsubscribed. Approximately 57% (12/21) completed either the 2- or 4-week questionnaires. Program satisfaction was high (overall mean 6.7, SD 0.8, range 1-7). Many perceived that the SMS text messaging program provided social support, companionship, and motivation to stop smoking. Messages about the health benefits of quitting were well received, whereas messages on how quitting cigarettes may prevent relapse from other substances had mixed views, highlighting the importance of tailoring interventions to patient preferences. CONCLUSIONS: SMS text messaging to promote smoking cessation and address SDOH needs may be an effective tool for improving quit rates and health outcomes in individuals with tobacco dependence and OUD. Our study adds to the growing body of evidence that SMS text messaging approaches are feasible and acceptable for providing tobacco treatment to all individuals who smoke, even among low-income populations who have OUD and are not ready to quit.

Hospitalization as an opportunity to engage underserved individuals in shared decision-making for lung cancer screening: results from two randomized pilot trials.

PURPOSE: Medicare requires tobacco dependence counseling and shared decision-making (SDM) for lung cancer screening (LCS) reimbursement. We hypothesized that initiating SDM during inpatient tobacco treatment visits would increase LCS among patients with barriers to proactively seeking outpatient preventive care. METHODS: We collected baseline assessments and performed two pilot randomized trials at our safety-net hospital. Pilot 1 tested feasibility, acceptability, and preliminary efficacy of a nurse practitioner initiating SDM for LCS during hospitalization (Inpatient SDM). We collected qualitative data on barriers encountered during Pilot 1. Pilot 2 added a community health worker (CHW) to address barriers to LCS completion (Inpatient SDM + CHW-navigation). For both studies, preliminary efficacy was an intention-to-treat analysis of LCS completion at 3 months between intervention and comparator (furnishing of LCS decision aid only) groups. RESULTS: Baseline assessments showed that patients preferred in-person LCS discussions versus self-reviewing materials; overall 20% had difficulty understanding written information. In Pilot 1, 4% (2/52) in Inpatient SDM versus 2% (1/48, comparator) completed LCS (p = 0.6), despite 89% (89/100) desiring LCS. Primary care providers noted that competing priorities and patient factors (e.g., social barriers to keeping appointments) prevented the intervention from working as intended. In Pilot 2, 50% (5/10) in Inpatient SDM + CHW-navigation versus 9% (1/11, comparator) completed LCS (p < 0.05). Many patients were ineligible due to recent diagnostic chest CT (Pilot 1: 255/659; Pilot 2: 239/527). CONCLUSIONS: Inpatient SDM + CHW-navigation shows promise to improve LCS rates among underserved patients who smoke, but feasibility is limited by recent diagnostic chest CT among inpatients. Implementing CHW-navigation in other clinical settings may facilitate LCS for underserved patients. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT03276806 (8 September 2017); NCT03793894 (4 January 2019).

Estimation of local time-varying reproduction numbers in noisy surveillance data.

A valuable metric in understanding local infectious disease dynamics is the local time-varying reproduction number, i.e. the expected number of secondary local cases caused by each infected individual. Accurate estimation of this quantity requires distinguishing cases arising from local transmission from those imported from elsewhere. Realistically, we can expect identification of cases as local or imported to be imperfect. We study the propagation of such errors in estimation of the local time-varying reproduction number. In addition, we propose a Bayesian framework for estimation of the true local time-varying reproduction number when identification errors exist. And we illustrate the practical performance of our estimator through simulation studies and with outbreaks of COVID-19 in Hong Kong and Victoria, Australia. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

Extending and Running the Mosquito Small RNA Genomics Resource Pipeline.

The Mosquito Small RNA Genomics (MSRG) resource is a repository of analyses on the small RNA transcriptomes of mosquito cell cultures and somatic and gonadal tissues. This resource allows for comparing the regulation dynamics of small RNAs generated from transposons and viruses across mosquito species. This chapter covers the procedures to set up the MSRG resource pipeline as a new installation by detailing the necessary collection of genome reference and annotation files and lists of microRNAs (miRNAs) hairpin sequences, transposon repeats consensus sequences, and virus genome sequences. Proper execution of the MSRG resource pipeline yields outputs amenable to biologists to further analyze with desktop and spreadsheet software to gain insights into the balance between arthropod endogenous small RNA populations and the proportions of virus-derived small RNAs that include Piwi-interacting RNAs (piRNAs) and endogenous small interfering RNAs (siRNAs).

Text-messaging to promote smoking cessation among individuals with opioid use disorder: quantitative and qualitative evaluation.

INTRODUCTION: Individuals with opioid use disorder (OUD) who smoke cigarettes have high tobacco-related comorbidities, lack of access to tobacco treatment, lack of inclusion in smoking cessation trials, and remain understudied in the mobile health field. The purpose of this study was to understand patients' with OUD perceptions of 1) text message programs to promote smoking cessation, 2) content and features to include in such a program, and 3) how message content should be framed. METHODS: From December 2018 to February 2019, we recruited 20 hospitalized individuals with a concurrent diagnosis of OUD and tobacco dependence at Boston Medical Center (BMC), the largest safety-net hospital in New England. We surveyed participants' cell phone use, their interest in a text message program to promote smoking cessation, and their reactions to and ratings of a series of 26 prototype texts. We then conducted open-ended interviews to elicit content and suggestions on how text message interventions can improve motivation to increase smoking cessation among individuals with OUD. The interviews also included open-ended inquiries exploring message ratings and message content, inquiries about preferences for message duration, frequency, and personalization. RESULTS: Quantitative analysis of questionnaire data indicated that the majority of participants owned a cell phone (95%, 19/20). Most participants (60%, 12/20) reported that they would be interested or very interested in receiving text messages about smoking cessation. Text messages about the health benefits of quitting were rated the highest among various categories of text messages. Qualitative analysis showed that almost every participant felt that text messages would help motivate smoking cessation given the support it would provide. CONCLUSIONS: This study demonstrates that individuals with OUD who smoke cigarettes perceive that a text message program designed to promote smoking cessation would motivate and support smoking cessation efforts. Our findings demonstrate that such a program is feasible as participants own cell phones, frequently send and receive text messages, and have unlimited text message plans. Findings from this study provide valuable insight into content and features to include when developing text message programs to address barriers to smoking cessation in individuals who have OUD and smoke cigarettes.

A mixed methods study to inform and evaluate a longitudinal nurse practitioner/community health worker intervention to address social determinants of health and chronic obstructive pulmonary disease self-management.

BACKGROUND: Individuals with low socioeconomic status experience higher prevalence and worse outcomes of chronic obstructive pulmonary disease (COPD). We undertook a quality improvement initiative at our safety net hospital in which a nurse practitioner (NP)/community health worker (CHW) team followed patients with COPD, frequent admissions, and unmet SDOH needs from hospitalization through one month post-discharge. We report our mixed methods approach to inform development and preliminary evaluation of this intervention. METHODS: We first assessed characteristics of patients admitted with COPD in 2018 (n = 1811), performing multivariable logistic regression to identify factors associated with ≥ 2 admissions per year. We then tested a standardized tool to screen for unmet SDOH needs in a convenience sample of 51 frequently hospitalized patients with COPD. From January-July 2019, we pilot tested the NP/CHW intervention with 57 patients, reviewed NP/CHW logs, and conducted qualitative interviews with 16 patient participants to explore impressions of the intervention. RESULTS: Patients with Medicaid insurance, mental health disorders, cardiac disease, and substance use disorder had increased odds of having ≥ 2 admissions. COPD severity, comorbidities, and unmet SDOH needs made COPD self-management challenging. Seventy-four percent of frequently admitted patients with COPD completing SDOH screening had unmet SDOH needs. Patients perceived that the NP/CHW intervention addressed these barriers by connecting them to resources and providing emotional support. CONCLUSIONS: Many patients with COPD admitted at our safety-net hospital experience unmet SDOH needs that impede COPD self-management. A longitudinal NP/CHW intervention to address unmet SDOH needs following discharge appears feasible and acceptable.

Estimation of local time-varying reproduction numbers in noisy surveillance data.

A valuable metric in understanding local infectious disease dynamics is the local time-varying reproduction number, i.e. the expected number of secondary local cases caused by each infected individual. Accurate estimation of this quantity requires distinguishing cases arising from local transmission from those imported from elsewhere. Realistically, we can expect identification of cases as local or imported to be imperfect. We study the propagation of such errors in estimation of the local time-varying reproduction number. In addition, we propose a Bayesian framework for estimation of the true local time-varying reproduction number when identification errors exist. And we illustrate the practical performance of our estimator through simulation studies and with outbreaks of COVID-19 in Hong Kong and Victoria, Australia.

Assessment of a COVID-19 Control Plan on an Urban University Campus During a Second Wave of the Pandemic.

Importance: The COVID-19 pandemic has severely disrupted US educational institutions. Given potential adverse financial and psychosocial effects of campus closures, many institutions developed strategies to reopen campuses in the fall 2020 semester despite the ongoing threat of COVID-19. However, many institutions opted to have limited campus reopening to minimize potential risk of spread of SARS-CoV-2. Objective: To analyze how Boston University (BU) fully reopened its campus in the fall of 2020 and controlled COVID-19 transmission despite worsening transmission in Boston, Massachusetts. Design, Setting, and Participants: This multifaceted intervention case series was conducted at a large urban university campus in Boston, Massachusetts, during the fall 2020 semester. The BU response included a high-throughput SARS-CoV-2 polymerase chain reaction testing facility with capacity to deliver results in less than 24 hours; routine asymptomatic screening for COVID-19; daily health attestations; adherence monitoring and feedback; robust contact tracing, quarantine, and isolation in on-campus facilities; face mask use; enhanced hand hygiene; social distancing recommendations; dedensification of classrooms and public places; and enhancement of all building air systems. Data were analyzed from December 20, 2020, to January 31, 2021. Main Outcomes and Measures: SARS-CoV-2 diagnosis confirmed by reverse transcription-polymerase chain reaction of anterior nares specimens and sources of transmission, as determined through contact tracing. Results: Between August and December 2020, BU conducted more than 500 000 COVID-19 tests and identified 719 individuals with COVID-19, including 496 students (69.0%), 11 faculty (1.5%), and 212 staff (29.5%). Overall, 718 individuals, or 1.8% of the BU community, had test results positive for SARS-CoV-2. Of 837 close contacts traced, 86 individuals (10.3%) had test results positive for COVID-19. BU contact tracers identified a source of transmission for 370 individuals (51.5%), with 206 individuals (55.7%) identifying a non-BU source. Among 5 faculty and 84 staff with SARS-CoV-2 with a known source of infection, most reported a transmission source outside of BU (all 5 faculty members [100%] and 67 staff members [79.8%]). A BU source was identified by 108 of 183 undergraduate students with SARS-CoV-2 (59.0%) and 39 of 98 graduate students with SARS-CoV-2 (39.8%); notably, no transmission was traced to a classroom setting. Conclusions and Relevance: In this case series of COVID-19 transmission, BU used a coordinated strategy of testing, contact tracing, isolation, and quarantine, with robust management and oversight, to control COVID-19 transmission in an urban university setting.

Prediction of genome-wide effects of single nucleotide variants on transcription factor binding.

Single nucleotide variants (SNVs) located in transcriptional regulatory regions can result in gene expression changes that lead to adaptive or detrimental phenotypic outcomes. Here, we predict gain or loss of binding sites for 741 transcription factors (TFs) across the human genome. We calculated 'gainability' and 'disruptability' scores for each TF that represent the likelihood of binding sites being created or disrupted, respectively. We found that functional cis-eQTL SNVs are more likely to alter TF binding sites than rare SNVs in the human population. In addition, we show that cancer somatic mutations have different effects on TF binding sites from different TF families on a cancer-type basis. Finally, we discuss the relationship between these results and cancer mutational signatures. Altogether, we provide a blueprint to study the impact of SNVs derived from genetic variation or disease association on TF binding to gene regulatory regions.

Effectiveness of an Opt-Out Electronic Heath Record-Based Tobacco Treatment Consult Service at an Urban Safety Net Hospital.

BACKGROUND: To address the burden of tobacco use in underserved populations, our safety net hospital developed a tobacco treatment intervention consisting of an "opt-out" electronic health record-based best practice alert + order set, which triggers consultation to an inpatient tobacco treatment consult (TTC) service for all hospitalized smokers. RESEARCH QUESTION: We sought to understand if the intervention would increase patient-level outcomes (receipt of tobacco treatment during hospitalization and at discharge; 6-month smoking abstinence) and improve hospital-wide performance on tobacco treatment metrics. DESIGN AND METHODS: We conducted two retrospective quasi-experimental analyses to examine effectiveness of the TTC service. Using a pragmatic design and multivariable logistic regression, we compared patient-level outcomes of receipt of nicotine replacement therapy and 6-month quit rates between smokers seen by the service (n = 505) and eligible smokers not seen because of time constraints (n = 680) between July 2016 and December 2016. In addition, we conducted an interrupted time series analysis to examine the effect of the TTC service on hospital-level performance measures, comparing reported Joint Commission measure rates for inpatient (Tob-2) and postdischarge (Tob-3) tobacco treatment preimplementation (January 2015-June 2016) vs postimplementation (July 2016-December 2017) of the intervention. RESULTS: Compared with inpatient smokers not seen by the TTC service, smokers seen by the TTC service had higher odds of receiving nicotine replacement during hospitalization (260 of 505 [51.5%] vs 244 of 680 [35.9%]; adjusted ORs [AOR], 1.93 [95% CI, 1.5-2.45]) and at discharge (164 of 505 [32.5%] vs 84 of 680 [12.4%]; AOR, 3.41 [95% CI, 2.54-4.61]), as well as higher odds of 6-month smoking abstinence (75 of 505 [14.9%] vs 68 of 680 [10%]; AOR, 1.48 [95% CI, 1.03-2.12]). Hospital-wide, the intervention was associated with a change in slope trends for Tob-3 (P < .01), but not for Tob-2. INTERPRETATION: The "opt-out" electronic health record-based TTC service at our large safety net hospital was effective at improving both patient-level outcomes and hospital-level performance metrics, and could be implemented at other safety net hospitals that care for hard-to-reach smokers.