Shared and unique transcriptomic signatures of antidepressant and probiotics action in the mammalian brain.

Understanding the shared and divergent mechanisms across antidepressant (AD) classes and probiotics is critical for improving treatment for mood disorders. Here we examine the transcriptomic effects of bupropion (NDRI), desipramine (SNRI), fluoxetine (SSRI) and a probiotic formulation (Lacidofil®) on 10 regions across the mammalian brain. These treatments massively alter gene expression (on average, 2211 differentially expressed genes (DEGs) per region-treatment combination), highlighting the biological complexity of AD and probiotic action. Intersection of DEG sets against neuropsychiatric GWAS loci, sex-specific transcriptomic portraits of major depressive disorder (MDD), and mouse models of stress and depression reveals significant similarities and differences across treatments. Interestingly, molecular responses in the infralimbic cortex, basolateral amygdala and locus coeruleus are region-specific and highly similar across treatments, whilst responses in the Raphe, medial preoptic area, cingulate cortex, prelimbic cortex and ventral dentate gyrus are predominantly treatment-specific. Mechanistically, ADs concordantly downregulate immune pathways in the amygdala and ventral dentate gyrus. In contrast, protein synthesis, metabolism and synaptic signaling pathways are axes of variability among treatments. We use spatial transcriptomics to further delineate layer-specific molecular pathways and DEGs within the prefrontal cortex. Our study reveals complex AD and probiotics action on the mammalian brain and identifies treatment-specific cellular processes and gene targets associated with mood disorders.

Comprehensive Cardiovascular Risk Factor Control With a Mobile Health Cardiovascular Risk Self-Management Program.

BACKGROUND: Mobile health technology's impact on cardiovascular risk factor control is not fully understood. This study evaluates the association between interaction with a mobile health application and change in cardiovascular risk factors. METHODS AND RESULTS: Participants with hypertension with or without dyslipidemia enrolled in a workplace-deployed mobile health application-based cardiovascular risk self-management program between January 2018 and December 2022. Retrospective evaluation explored the influence of application engagement on change in blood pressure (BP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and weight. Multiple regression analyses examined the influence of guideline-based, nonpharmacological lifestyle-based digital coaching on outcomes adjusting for confounders. Of 102 475 participants, 49.1% were women. Median age was 53 (interquartile range, 43-61) years, BP was 134 (interquartile range, 124-144)/84 (interquartile range, 78-91) mm Hg, TC was 183 (interquartile range, 155-212) mg/dL, LDL-C was 106 (82-131) mg/dL, and body mass index was 30 (26-35) kg/m2. At 2 years, participants with baseline systolic BP ≥140 mm Hg reduced systolic BP by 18.6 (SEM, 0.3) mm Hg. At follow up, participants with baseline TC ≥240 mg/dL reduced TC by 65.7 (SEM, 4.6) mg/dL, participants with baseline LDL-C≥160 mg/dL reduced LDL-C by 66.6 (SEM, 6.2) mg/dL, and participants with baseline body mass index ≥30 kg/m2 lost 12.0 (SEM, 0.3) pounds, or 5.1% of body weight. Interaction with digital coaching was associated with greater reduction in all outcomes. CONCLUSIONS: A mobile health application-based cardiovascular risk self-management program was associated with favorable reductions in BP, TC, LDL-C, and weight, highlighting the potential use of this technology in comprehensive cardiovascular risk factor control.

Pharmacoinformatics-enabled Interventions Improved Care Coordination and Identified Pharmacy-Related Safety Issues in a Multicultural Medicare Population.

BACKGROUND: Compared to White populations, multicultural older adults experience more gaps in preventive care (e.g., vaccinations, screenings, chronic condition monitoring), social determinants of health barriers (e.g., access to care, language, transportation), and disparities and inequities (e.g., comorbidities, disease burden, and health care costs). OBJECTIVES: This study aims to describe an informatics-based approach used to execute and evaluate results of a member-centric, pharmacoinformatics-informed engagement program to deliver culturally tailored microinterventions to close medication-related gaps in care utilizing multidisciplinary care coordination that leverages the expanded role of the pharmacist. The operational framework will be described, and the influence of the medication use processes will be reported in a multicultural Medicare Advantage cohort. METHODS: A pharmacoinformatics framework was leveraged to conduct a retrospective, observational cohort analysis of the program. Claims data were used to evaluate the influence of medication use process microinterventions from a large Medicare Advantage cohort of members who self-identify as Black and/or Hispanic, and have type 2 diabetes mellitus and/or hypertension, and meet eligibility criteria for multidisciplinary (e.g., nursing and pharmacy) care management (CM) and received pharmacy referral from January 1, 2022, through September 30, 2023. RESULTS: A total of 3,265 Medicare Advantage members (78.3% Black and 21.7% Hispanic) received CM and pharmacy referral. Pharmacovigilance reviews conducted during this timeframe identified 258 acute events that escalated member CM. Provider outreach (n = 185) informed of safety issues (drug duplication, n = 48; drug interactions, n = 21; drug-disease interactions, n = 5; noncompliance and/or dosing issues, n = 27). Outreach to members (n = 160) and providers (n = 164) informed of open quality-related measure gaps for medication adherence. CONCLUSION: The application of pharmacoinformatics by a payor-led multicultural clinical program demonstrated quality improvements in Medicare Advantage member identification including risk stratification, timely outreach for pharmacy-related safety issues, and improved efficiency of multidisciplinary care coordination involving medication use process workflows.

Comprehensiveness, Accuracy, and Readability of Exercise Recommendations Provided by an AI-Based Chatbot: Mixed Methods Study.

BACKGROUND: Regular physical activity is critical for health and disease prevention. Yet, health care providers and patients face barriers to implement evidence-based lifestyle recommendations. The potential to augment care with the increased availability of artificial intelligence (AI) technologies is limitless; however, the suitability of AI-generated exercise recommendations has yet to be explored. OBJECTIVE: The purpose of this study was to assess the comprehensiveness, accuracy, and readability of individualized exercise recommendations generated by a novel AI chatbot. METHODS: A coding scheme was developed to score AI-generated exercise recommendations across ten categories informed by gold-standard exercise recommendations, including (1) health condition-specific benefits of exercise, (2) exercise preparticipation health screening, (3) frequency, (4) intensity, (5) time, (6) type, (7) volume, (8) progression, (9) special considerations, and (10) references to the primary literature. The AI chatbot was prompted to provide individualized exercise recommendations for 26 clinical populations using an open-source application programming interface. Two independent reviewers coded AI-generated content for each category and calculated comprehensiveness (%) and factual accuracy (%) on a scale of 0%-100%. Readability was assessed using the Flesch-Kincaid formula. Qualitative analysis identified and categorized themes from AI-generated output. RESULTS: AI-generated exercise recommendations were 41.2% (107/260) comprehensive and 90.7% (146/161) accurate, with the majority (8/15, 53%) of inaccuracy related to the need for exercise preparticipation medical clearance. Average readability level of AI-generated exercise recommendations was at the college level (mean 13.7, SD 1.7), with an average Flesch reading ease score of 31.1 (SD 7.7). Several recurring themes and observations of AI-generated output included concern for liability and safety, preference for aerobic exercise, and potential bias and direct discrimination against certain age-based populations and individuals with disabilities. CONCLUSIONS: There were notable gaps in the comprehensiveness, accuracy, and readability of AI-generated exercise recommendations. Exercise and health care professionals should be aware of these limitations when using and endorsing AI-based technologies as a tool to support lifestyle change involving exercise.

Sex and cell-specific gene expression in corticolimbic brain regions associated with psychiatric disorders revealed by bulk and single-nuclei RNA sequencing.

BACKGROUND: There are sex-specific differences in the prevalence, symptomology and course of psychiatric disorders. However, preclinical models have primarily used males, such that the molecular mechanisms underlying sex-specific differences in psychiatric disorders are not well established. METHODS: In this study, we compared transcriptome-wide gene expression profiles in male and female rats within the corticolimbic system, including the cingulate cortex, nucleus accumbens medial shell (NAcS), ventral dentate gyrus and the basolateral amygdala (n = 22-24 per group/region). FINDINGS: We found over 3000 differentially expressed genes (DEGs) in the NAcS between males and females. Of these DEGs in the NAcS, 303 showed sex-dependent conservation DEGs in humans and were significantly enriched for gene ontology terms related to blood vessel morphogenesis and regulation of cell migration. Single nuclei RNA sequencing in the NAcS of male and female rats identified widespread sex-dependent expression, with genes upregulated in females showing a notable enrichment for synaptic function. Female upregulated genes in astrocytes, Drd3+MSNs and oligodendrocyte were also enriched in several psychiatric genome-wide association studies (GWAS). INTERPRETATION: Our data provide comprehensive evidence of sex- and cell-specific molecular profiles in the NAcS. Importantly these differences associate with anxiety, bipolar disorder, schizophrenia, and cross-disorder, suggesting an intrinsic molecular basis for sex-based differences in psychiatric disorders that strongly implicates the NAcS. FUNDING: This work was supported by funding from the Hope for Depression Research Foundation (MJM).

Clinical use of artificial intelligence requires AI-capable organizations.

Artificial intelligence-based algorithms are being widely implemented in health care, even as evidence is emerging of bias in their design, problems with implementation, and potential harm to patients. To achieve the promise of using of AI-based tools to improve health, healthcare organizations will need to be AI-capable, with internal and external systems functioning in tandem to ensure the safe, ethical, and effective use of AI-based tools. Ideas are starting to emerge about the organizational routines, competencies, resources, and infrastructures that will be required for safe and effective deployment of AI in health care, but there has been little empirical research. Infrastructures that provide legal and regulatory guidance for managers, clinician competencies for the safe and effective use of AI-based tools, and learner-centric resources such as clear AI documentation and local health ecosystem impact reviews can help drive continuous improvement.

Diverse environmental bacteria displaying activity against Phakopsora pachyrhizi, the cause of soybean rust.

The management of soybean rust (SBR) caused by the obligate fungus Phakopsora pachyrhizi mostly relies on the use of synthetic fungicides, especially in areas where the disease inflicts serious yield losses. The reliance on synthetic fungicides to manage this disease has resulted in resistance of P. pachyrhizi populations to most fungicides. In this study, bacteria isolated from diverse environments were evaluated for their biocontrol potential against P. pachyrhizi using soybean detached-leaf method and on-plant in the growth chamber, greenhouse, and field. Among 998 bacterial isolates evaluated using the detached-leaf method; 58% were isolated from plant-related materials, 27% from soil, 10% from insects, and 5% from other environments. Of the isolates screened, 73 were active (they had ⪖ 75% rust reduction) with an active rate of 7.3%. From the active isolates, 65 isolates were re-tested on-plant in the growth chamber for activity confirmation. In the confirmation test, 49 bacteria isolated from plant-related materials maintained their activity with a confirmation rate of 75%. The majority of bacteria with confirmed activity belonged to the taxonomic classes Bacilli and Gammaproteobacteria (70%). Active isolates were prioritized for greenhouse and field testing based on activity in the initial screen and confirmation test. Six bacterial isolates AFS000009 (Pseudomonas_E chlororaphis), AFS032321 (Bacillus subtilis), AFS042929 (Bacillus_C megaterium), AFS065981 (Bacillus_X simplex_A), AFS090698 (Bacillus_A thuringiensis_S), and AFS097295 (Bacillus_A toyonensis) were selected from those bacteria that maintained activity in the confirmation test and were evaluated in the greenhouse, and five among them were evaluated in the field. From the Alabama field evaluation, all bacterial isolates reduced rust infection as well as azoxystrobin (Quadris® at 0.3 L/ha) used as the fungicide control (P > 0.05). Moreover, the scanning electron micrographs demonstrated evidence of antagonistic activity of AFS000009 and AFS032321 against P. pachyrhizi urediniospores. Bacterial isolates that consistently showed activity comparable to that of azoxystrobin can be improved through fermentation and formulation optimization, developed, and deployed. These bacteria strains would provide a valuable alternative to the synthetic fungicides and could play a useful role in integrated disease management programs for this disease.

Competencies for the Use of Artificial Intelligence-Based Tools by Health Care Professionals.

PURPOSE: The expanded use of clinical tools that incorporate artificial intelligence (AI) methods has generated calls for specific competencies for effective and ethical use. This qualitative study used expert interviews to define AI-related clinical competencies for health care professionals. METHOD: In 2021, a multidisciplinary team interviewed 15 experts in the use of AI-based tools in health care settings about the clinical competencies health care professionals need to work effectively with such tools. Transcripts of the semistructured interviews were coded and thematically analyzed. Draft competency statements were developed and provided to the experts for feedback. The competencies were finalized using a consensus process across the research team. RESULTS: Six competency domain statements and 25 subcompetencies were formulated from the thematic analysis. The competency domain statements are: (1) basic knowledge of AI: explain what AI is and describe its health care applications; (2) social and ethical implications of AI: explain how social, economic, and political systems influence AI-based tools and how these relationships impact justice, equity, and ethics; (3) AI-enhanced clinical encounters: carry out AI-enhanced clinical encounters that integrate diverse sources of information in creating patient-centered care plans; (4) evidence-based evaluation of AI-based tools: evaluate the quality, accuracy, safety, contextual appropriateness, and biases of AI-based tools and their underlying data sets in providing care to patients and populations; (5) workflow analysis for AI-based tools: analyze and adapt to changes in teams, roles, responsibilities, and workflows resulting from implementation of AI-based tools; and (6) practice-based learning and improvement regarding AI-based tools: participate in continuing professional development and practice-based improvement activities related to use of AI tools in health care. CONCLUSIONS: The 6 clinical competencies identified can be used to guide future teaching and learning programs to maximize the potential benefits of AI-based tools and diminish potential harms.

Real-world Application of Racial and Ethnic Imputation and Cohort Balancing Techniques to Deliver Equitable Clinical Trial Recruitment.

Enhancing diversity and inclusion in clinical trial recruitment, especially for historically marginalized populations including Black, Indigenous, and People of Color individuals, is essential. This practice ensures that generalizable trial results are achieved to deliver safe, effective, and equitable health and healthcare. However, recruitment is limited by two inextricably linked barriers - the inability to recruit and retain enough trial participants, and the lack of diversity amongst trial populations whereby racial and ethnic groups are underrepresented when compared to national composition. To overcome these barriers, this study describes and evaluates a framework that combines 1) probabilistic and machine learning models to accurately impute missing race and ethnicity fields in real-world data including medical and pharmacy claims for the identification of eligible trial participants, 2) randomized controlled trial experimentation to deliver an optimal patient outreach strategy, and 3) stratified sampling techniques to effectively balance cohorts to continuously improve engagement and recruitment metrics.

Leveraging Clinical Informatics to Address the Quintuple Aim for End-of-Life Care.

As the population of older adults grows at an unprecedented rate, there is a large gap to provide culturally tailored end-of-life care. This study describes a payor-led, informatics-based approach to identify Medicare members who may benefit from a Compassionate CareSM Program (CCP), which was designed to provide specialized care management services and support to members who have end-stage and/or life-limiting illnesses by addressing the quintuple aim. Potential participants are identified through machine learning models whereby nurse care managers then provide tailored outreach via telephone. A retrospective, observational cohort analysis of propensity-weighted Medicare members was performed to compare decedents who did or did not participate in the CCP. This program enhanced the end-of-life care experience while providing equitable outcomes regardless of age, gender, and geography and decreased inpatient (-37%) admissions with concomitant reduced (-59%) medical spend when compared to decedents that did not utilize the end-of-life care management program.

Considering Clinician Competencies for the Implementation of Artificial Intelligence-Based Tools in Health Care: Findings From a Scoping Review.

BACKGROUND: The use of artificial intelligence (AI)-based tools in the care of individual patients and patient populations is rapidly expanding. OBJECTIVE: The aim of this paper is to systematically identify research on provider competencies needed for the use of AI in clinical settings. METHODS: A scoping review was conducted to identify articles published between January 1, 2009, and May 1, 2020, from MEDLINE, CINAHL, and the Cochrane Library databases, using search queries for terms related to health care professionals (eg, medical, nursing, and pharmacy) and their professional development in all phases of clinical education, AI-based tools in all settings of clinical practice, and professional education domains of competencies and performance. Limits were provided for English language, studies on humans with abstracts, and settings in the United States. RESULTS: The searches identified 3476 records, of which 4 met the inclusion criteria. These studies described the use of AI in clinical practice and measured at least one aspect of clinician competence. While many studies measured the performance of the AI-based tool, only 4 measured clinician performance in terms of the knowledge, skills, or attitudes needed to understand and effectively use the new tools being tested. These 4 articles primarily focused on the ability of AI to enhance patient care and clinical decision-making by improving information flow and display, specifically for physicians. CONCLUSIONS: While many research studies were identified that investigate the potential effectiveness of using AI technologies in health care, very few address specific competencies that are needed by clinicians to use them effectively. This highlights a critical gap.

The development and implementation of a new hospital performance measure to assess hospital contributions to community health and equity.

OBJECTIVE: To develop and implement a measure of how US hospitals contribute to community health with a focus on equity. DATA SOURCES: Primary data from public comments and hospital surveys and secondary data from the IBM Watson Top 100 Hospitals program collected in the United States in 2020 and 2021. STUDY DESIGN: A thematic analysis of public comments on the proposed measure was conducted using an iterative grounded approach for theme identification. A cross-sectional survey of 207 hospitals was conducted to assess self-attestation to 28 community health best practice standards in the revised measure. An analysis of hospital rankings before and after inclusion of the new measure was performed. DATA COLLECTION/EXTRACTION METHODS: Public comment on the proposed measure was collected via an online survey, email, and virtual meetings in 2020. The survey of hospitals was conducted online by IBM in 2021. The analysis of hospital ranking compared the 2020 and 2021 IBM Watson Top 100 Hospitals program results. PRINCIPAL FINDINGS: More than 650 discrete comments from 83 stakeholders were received and analyzed during measure development. Key themes identified in thematic analysis included equity, fairness, and community priorities. Hospitals that responded to a cross-sectional survey reported meeting on average 76% of applicable best practice standards. Least met standards included providing emergent buprenorphine treatment for opioid use disorder (53%), supporting an evidence-based home visiting program (53%), and establishing a returning citizens employment program (27%). Thirty-seven hospitals shifted position in the 100 Top Hospital rankings after the inclusion of the new measure. CONCLUSIONS: There is broad interest in measuring hospital contributions to community health with a focus on equity. Many highly ranked hospitals report meeting best practice standards, but significant gaps remain. Improving measurement to incentivize greater hospital contributions to community health and equity is an important priority.

Digital Health Interventions to Enhance Prevention in Primary Care: Scoping Review.

BACKGROUND: Disease prevention is a central aspect of primary care practice and is comprised of primary (eg, vaccinations), secondary (eg, screenings), tertiary (eg, chronic condition monitoring), and quaternary (eg, prevention of overmedicalization) levels. Despite rapid digital transformation of primary care practices, digital health interventions (DHIs) in preventive care have yet to be systematically evaluated. OBJECTIVE: This review aimed to identify and describe the scope and use of current DHIs for preventive care in primary care settings. METHODS: A scoping review to identify literature published from 2014 to 2020 was conducted across multiple databases using keywords and Medical Subject Headings terms covering primary care professionals, prevention and care management, and digital health. A subgroup analysis identified relevant studies conducted in US primary care settings, excluding DHIs that use the electronic health record (EHR) as a retrospective data capture tool. Technology descriptions, outcomes (eg, health care performance and implementation science), and study quality as per Oxford levels of evidence were abstracted. RESULTS: The search yielded 5274 citations, of which 1060 full-text articles were identified. Following a subgroup analysis, 241 articles met the inclusion criteria. Studies primarily examined DHIs among health information technologies, including EHRs (166/241, 68.9%), clinical decision support (88/241, 36.5%), telehealth (88/241, 36.5%), and multiple technologies (154/241, 63.9%). DHIs were predominantly used for tertiary prevention (131/241, 54.4%). Of the core primary care functions, comprehensiveness was addressed most frequently (213/241, 88.4%). DHI users were providers (205/241, 85.1%), patients (111/241, 46.1%), or multiple types (89/241, 36.9%). Reported outcomes were primarily clinical (179/241, 70.1%), and statistically significant improvements were common (192/241, 79.7%). Results were summarized across the following 5 topics for the most novel/distinct DHIs: population-centered, patient-centered, care access expansion, panel-centered (dashboarding), and application-driven DHIs. The quality of the included studies was moderate to low. CONCLUSIONS: Preventive DHIs in primary care settings demonstrated meaningful improvements in both clinical and nonclinical outcomes, and across user types; however, adoption and implementation in the US were limited primarily to EHR platforms, and users were mainly clinicians receiving alerts regarding care management for their patients. Evaluations of negative results, effects on health disparities, and many other gaps remain to be explored.

Effectiveness of Contact Tracing for Viral Disease Mitigation and Suppression: Evidence-Based Review.

BACKGROUND: Contact tracing in association with quarantine and isolation is an important public health tool to control outbreaks of infectious diseases. This strategy has been widely implemented during the current COVID-19 pandemic. The effectiveness of this nonpharmaceutical intervention is largely dependent on social interactions within the population and its combination with other interventions. Given the high transmissibility of SARS-CoV-2, short serial intervals, and asymptomatic transmission patterns, the effectiveness of contact tracing for this novel viral agent is largely unknown. OBJECTIVE: This study aims to identify and synthesize evidence regarding the effectiveness of contact tracing on infectious viral disease outcomes based on prior scientific literature. METHODS: An evidence-based review was conducted to identify studies from the PubMed database, including preprint medRxiv server content, related to the effectiveness of contact tracing in viral outbreaks. The search dates were from database inception to July 24, 2020. Outcomes of interest included measures of incidence, transmission, hospitalization, and mortality. RESULTS: Out of 159 unique records retrieved, 45 (28.3%) records were reviewed at the full-text level, and 24 (15.1%) records met all inclusion criteria. The studies included utilized mathematical modeling (n=14), observational (n=8), and systematic review (n=2) approaches. Only 2 studies considered digital contact tracing. Contact tracing was mostly evaluated in combination with other nonpharmaceutical interventions and/or pharmaceutical interventions. Although some degree of effectiveness in decreasing viral disease incidence, transmission, and resulting hospitalizations and mortality was observed, these results were highly dependent on epidemic severity (R0 value), number of contacts traced (including presymptomatic and asymptomatic cases), timeliness, duration, and compliance with combined interventions (eg, isolation, quarantine, and treatment). Contact tracing effectiveness was particularly limited by logistical challenges associated with increased outbreak size and speed of infection spread. CONCLUSIONS: Timely deployment of contact tracing strategically layered with other nonpharmaceutical interventions could be an effective public health tool for mitigating and suppressing infectious outbreaks by decreasing viral disease incidence, transmission, and resulting hospitalizations and mortality.

Effectiveness of non-pharmaceutical interventions related to social distancing on respiratory viral infectious disease outcomes: A rapid evidence-based review and meta-analysis.

OBJECTIVES: Non-pharmaceutical interventions (e.g. quarantine and isolation) are used to mitigate and control viral infectious disease, but their effectiveness has not been well studied. For COVID-19, disease control efforts will rely on non-pharmaceutical interventions until pharmaceutical interventions become widely available, while non-pharmaceutical interventions will be of continued importance thereafter. METHODS: This rapid evidence-based review provides both qualitative and quantitative analyses of the effectiveness of social distancing non-pharmaceutical interventions on disease outcomes. Literature was retrieved from MEDLINE, Google Scholar, and pre-print databases (BioRxiv.org, MedRxiv.org, and Wellcome Open Research). RESULTS: Twenty-eight studies met inclusion criteria (n = 28). Early, sustained, and combined application of various non-pharmaceutical interventions could mitigate and control primary outbreaks and prevent more severe secondary or tertiary outbreaks. The strategic use of non-pharmaceutical interventions decreased incidence, transmission, and/or mortality across all interventions examined. The pooled attack rates for no non-pharmaceutical intervention, single non-pharmaceutical interventions, and multiple non-pharmaceutical interventions were 42% (95% confidence interval = 30% - 55%), 29% (95% confidence interval = 23% - 36%), and 22% (95% confidence interval = 16% - 29%), respectively. CONCLUSION: Implementation of multiple non-pharmaceutical interventions at key decision points for public health could effectively facilitate disease mitigation and suppression until pharmaceutical interventions become available. Dynamics around R 0 values, the susceptibility of certain high-risk patient groups to infection, and the probability of asymptomatic cases spreading disease should be considered.

Leveraging artificial intelligence for pandemic preparedness and response: a scoping review to identify key use cases.

Artificial intelligence (AI) represents a valuable tool that could be widely used to inform clinical and public health decision-making to effectively manage the impacts of a pandemic. The objective of this scoping review was to identify the key use cases for involving AI for pandemic preparedness and response from the peer-reviewed, preprint, and grey literature. The data synthesis had two parts: an in-depth review of studies that leveraged machine learning (ML) techniques and a limited review of studies that applied traditional modeling approaches. ML applications from the in-depth review were categorized into use cases related to public health and clinical practice, and narratively synthesized. One hundred eighty-three articles met the inclusion criteria for the in-depth review. Six key use cases were identified: forecasting infectious disease dynamics and effects of interventions; surveillance and outbreak detection; real-time monitoring of adherence to public health recommendations; real-time detection of influenza-like illness; triage and timely diagnosis of infections; and prognosis of illness and response to treatment. Data sources and types of ML that were useful varied by use case. The search identified 1167 articles that reported on traditional modeling approaches, which highlighted additional areas where ML could be leveraged for improving the accuracy of estimations or projections. Important ML-based solutions have been developed in response to pandemics, and particularly for COVID-19 but few were optimized for practical application early in the pandemic. These findings can support policymakers, clinicians, and other stakeholders in prioritizing research and development to support operationalization of AI for future pandemics.