Program evaluation is a critical tool for understanding and improving organizational activities and systems. This report updates the 1999 CDC Framework for Program Evaluation in Public Health (CDC. Framework for program evaluation in public health. MMWR Recomm Rep 1999;48[No. RR-11];1-40) by integrating major advancements in the fields of evaluation and public health, lessons learned from practical applications of the original framework, and current Federal agency policies and practices. A practical, nonprescriptive tool, the updated 2024 framework is designed to summarize and organize essential elements of program evaluation, and can be applied at any level from individual programs to broader systems by novices and experts for planning and implementing an evaluation. Although many of the key aspects from the 1999 framework remain, certain key differences exist. For example, this updated framework also includes six steps that describe the general process of evaluation planning and implementation, but some content and step names have changed (e.g., the first step has been renamed Assess context). The standards for high-quality evaluation remain central to the framework, although they have been updated to the five Federal evaluation standards. The most substantial change from the 1999 framework is the addition of three cross-cutting actions that are core tenets to incorporate within each evaluation step: engage collaboratively, advance equity, and learn from and use insights. The 2024 framework provides a guide for designing and conducting evaluation across many topics within and outside of public health that anyone involved in program evaluation efforts can use alone or in conjunction with other evaluation approaches, tools, or methods to build evidence, understand programs, and refine evidence-based decision-making to improve all program outcomes.

Evaluation can ensure the quality of public health programs. Systematic efforts to identify and fully engage everyone involved with or affected by a program can provide critical information about asthma programs and the broader environment in which they operate. To assist evaluators working at programs funded by the Centers for Disease Control and Prevention (CDC's) National Asthma Control Program (NACP), we developed a package of tools that build on the CDC's 1999 Framework for Program Evaluation in Public Health. The resulting suite of evaluation tools guides evaluators through a structured but flexible process, engaging a diverse array of interest holders and actively involving them in evaluation planning and implementation, all while strengthening their capacity to meaningfully contribute to the evaluation process. For our newest tool, our team reviewed the recent evaluation literature to create an enhanced version of the 1999 framework that describes important elements of professional evaluation practice. Although the original framework describes the steps to take in conducting an evaluation and the standards for a high-quality evaluation, our enhanced framework includes an explanation of how evaluators should approach their work: by incorporating critical reflection, interpersonal competence, situational awareness, and cultural responsiveness. In this article, we highlight many of the evaluation resources our team has created since the NACP's inception, culminating in a free e-text called Planting the Seeds of High-Quality Program Evaluation in Public Health. Public health professionals working in many types of programs - not just asthma - may find these resources useful.

After the hurricanes in 2017 in the U.S. Caribbean, it was essential to rebuild, strengthen, and sustain essential environmental health (EH) services and systems. The National Environmental Health Association, in partnership with the Centers for Disease Control and Prevention, developed an online mentorship program for newly hired and existing EH staff and health department leadership in Caribbean health departments. Participants were provided with both practical and didactic learning and were allowed to evaluate the program. Both mentors and mentees were highly satisfied with the knowledge and skills acquired, and mentees expressed it was relevant to their daily work. Based on the findings, we recommend both an online and a hybrid mentorship program for leadership- and inspector-level workforces in EH and potentially in other fields.

INTRODUCTION: Postpartum hemorrhage (PPH) is a significant cause of maternal mortality worldwide, particularly in low- and middle-income countries. It is essential to develop effective prediction models to identify women at risk of PPH and implement appropriate interventions to reduce maternal morbidity and mortality. This study aims to predict the occurrence of postpartum hemorrhage using machine learning models based on antenatal, intrapartum, and postnatal visit data obtained from the Kenya Antenatal and Postnatal Care Research Collective cohort. METHOD: Four machine learning models - logistic regression, naïve Bayes, decision tree, and random forest - were constructed using 67% training data (1,056/1,576). The training data was further split into 67% for model building and 33% cross validation. Once the models are built, the remaining 33% (520/1,576) independent test data was used for external validation to confirm the models' performance. Models were fine-tuned using feature selection through extra tree classifier technique. Model performance was assessed using accuracy, sensitivity, and area under the curve (AUC) of the receiver operating characteristics (ROC) curve. RESULT: The naïve Bayes model performed best with 0.95 accuracy, 0.97 specificity, and 0.76 AUC. Seven factors (anemia, limited prenatal care, hemoglobin concentrations, signs of pallor at intrapartum, intrapartum systolic blood pressure, intrapartum diastolic blood pressure, and intrapartum respiratory rate) were associated with PPH prediction in Kenyan population. DISCUSSION: This study demonstrates the potential of machine learning models in predicting PPH in the Kenyan population. Future studies with larger datasets and more PPH cases should be conducted to improve prediction performance of machine learning model. Such prediction algorithms would immensely help to construct a personalized obstetric path for each pregnant patient, improve resource allocation, and reduce maternal mortality and morbidity.

Background: Beginning in March 2021, Mexico vaccinated childcare workers with a single-dose CanSino Biologics (Adv5-nCoV) COVID-19 vaccine. Although CanSino is currently approved for use in 10 Latin American, Asian, and European countries, little information is available about its vaccine effectiveness (VE). Method(s): We evaluated CanSino VE within a childcare worker cohort that included 1,408 childcare facilities. Participants were followed during March-December 2021 and tested through SARS-CoV-2 RT-PCR or rapid antigen test if they developed any symptom compatible with COVID-19. Vaccination status was obtained through worker registries. VE was calculated as 100% x (1-hazard ratio for SARS-CoV-2 infection in fully vaccinated vs. unvaccinated participants), using an Andersen-Gill model adjusted for age, sex, state, and local viral circulation. Result(s): The cohort included 43,925 persons who were mostly (96%) female with a median age of 32 years; 37,646 (86%) were vaccinated with CanSino. During March-December 2021, 2,250 (5%) participants had laboratory-confirmed COVID-19, of whom 25 were hospitalized and 6 died. Adjusted VE was 20% (95% CI = 10-29%) against illness, 76% (42-90%) against hospitalization, and 94% (66-99%) against death. VE against illness declined from 48% (95% CI = 33-61) after 14-60 days following full vaccination to 20% (95% CI = 9-31) after 61-120 days. Conclusion(s): CanSino vaccine was effective at preventing COVID-19 illness and highly effective at preventing hospitalization and death. It will be useful to further evaluate duration of protection and assess the value of booster doses to prevent COVID-19 and severe outcomes. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2 prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3212 excess deaths (95% CrI: 2104-4591), representing an 18.5% (95% CrI: 13.0-25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortality patterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences.

Although evaluative thinking lies at the heart of what we do as evaluators and what we hope to promote in others through our efforts to build evaluation capacity, researchers have given limited attention to measuring this concept. We undertook a research study to better understand how instances of evaluative thinking may present in practice-based settings-specifically within four state asthma control programs funded by the Centers for Disease Control and Prevention's National Asthma Control Program. Through content analyses of documents as well as interviews and a subsequent focus group with four state asthma control programs' evaluators and program managers we identified and defined twenty-two indicators of evaluative thinking. Findings provide insights about what practitioners may wish to look for when they intend to build evaluative thinking and the types of data sources that may be more or less helpful in such efforts.

The article discusses the Revised 10 Essential Public Health Services and its application to the practice of environmental public health in 2023. Topics covered include key changes in the revision, and environmental health programs' possible help in delivering the 10 Essential Services in their communities, and support of broader public health initiatives. Also given is the resource located at www.cdc.gov/nceh/ehs/10-essential-services/index.html.

An author's name was misspelled in the byline on page 1420. “Keri N. Atlhoff” should read “Keri N. Althoff.” The error has been corrected in the published article.

Boron nitride nanotubes (BNNT) are produced by many different methods leading to variances in physicochemical characteristics and impurities in the final product. These differences can alter the toxicity profile. The importance of understanding the potential pathological implications of this high aspect ratio nanomaterial is increasing as new approaches to synthesize and purify in large scale are being developed. In this review, we discuss the various factors of BNNT production that can influence its toxicity followed by summarizing the toxicity findings from in vitro and in vivo studies conducted to date, including a review of particle clearance observed with various exposure routes. To understand the risk to workers and interpret relevance of toxicological findings, exposure assessment at manufacturing facilities was discussed. Workplace exposure assessment of BNNT from two manufacturing facilities measured boron concentrations in personal breathing zones from non-detectable to 0.95 µg/m3 and TEM structure counts of 0.0123 ± 0.0094 structures/cm3, concentrations well below what was found with other engineered high aspect ratio nanomaterials like carbon nanotubes and nanofibers. Finally, using a purified BNNT, a “read-across” toxicity assessment was performed to demonstrate how known hazard data and physicochemical characteristics can be utilized to evaluate potential inhalation toxicity concerns. Graphical [Figure not available: see fulltext.]. © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Adjuvants can increase the magnitude and durability of the immune response generated by the vaccine antigen. Aluminum salts (Alum) remain the main adjuvant licensed for human use. A few new adjuvants have been licensed for use in human vaccines since the 1990s. QS-21, a mixture of saponin compounds, was included in the AS01-adjuvanted Shingrix vaccine. Here, we investigated the adjuvant effects of VSA-1, a newly developed semisynthetic analog of QS-21, on promoting protection in mice after vaccination with the inactivated split virus vaccine. The adjuvant effects of VSA-1 on improving vaccine efficacy after prime immunization were evident as shown by significantly higher levels of hemagglutination-inhibiting antibody titers and enhanced homologous protection compared to those by QS-21 and Alum adjuvants. The adjuvant effects of VSA-1 on enhancing heterosubtypic protection after two doses of adjuvanted vaccination were comparable to those of QS-21. T cell immunity played an important role in conferring cross-protection by VSA-1-adjuvanted vaccination. Overall, the findings in this study suggest that VSA-1 exhibits desirable adjuvant properties and a unique pattern of innate and adaptive immune responses, contributing to improved homologous and heterosubtypic protection by inactivated split influenza vaccination in mice.

In 2016 the United States Centers for Disease Control and Prevention (CDC) established a Nuclear/Radiological Training and Exercise Preparedness (TEP) Program to better prepare its workforce to respond to a nuclear/radiological incident. The TEP program is comprised of staff across CDC programs with a variety of specialties such as epidemiologists, clinicians, data managers, communicators, environmental health specialists, at risk population specialists and health physicists. Key TEP activities include the preparation of the CDC Nuclear/Radiological Incident Response and Recovery Annex that describes CDC's roles and responsibilities in the event of a nuclear/radiological incident; establishment of an Incident Management System (IMS) structure to reflect an agency-wide response consistent with CDC's All Hazards Plan; and completion of nuclear/radiological public health preparedness and response training and exercises. In addition to training sessions on the various radiation topics, the TEP program includes seminars on the various roles and responsibilities of the task forces defined in IMS during a response. The TEP program includes a range of discussion-based (seminars, workshops, tabletop exercises) and operations-based (drills and functional exercises) activities aimed at enhancing IMS staff capabilities and capacity to be prepared to respond to a nuclear/radiological incident. In summary, the CDC's Nuclear/Radiological TEP Program prepares knowledgeable, well-trained staff, or a radiation-savvy workforce, ready for a robust response to a nuclear/radiological emergency.

With increasing use of rituximab and other B-cell depleting monoclonal antibodies for multiple indications, infectious complications are being recognized. We summarize clinical findings of patients on rituximab with arboviral diseases identified through literature review or consultation with the Centers for Disease Control and Prevention. We identified 21 patients on recent rituximab therapy who were diagnosed with an arboviral disease caused by West Nile, tick-borne encephalitis, eastern equine encephalitis, Cache Valley, Jamestown Canyon, and Powassan viruses. All reported patients had neuroinvasive disease. The diagnosis of arboviral infection required molecular testing in 20 (95%) patients. Median illness duration was 36 days (range, 12 days-1 year) and 15/19 (79%) patients died from their illness. Patients on rituximab with arboviral disease can have a severe or prolonged course with an absence of serologic response. Patients should be counseled about mosquito and tick bite prevention when receiving rituximab and other B-cell depleting therapies.

BACKGROUND: In 2012, the US Department of Health and Human Services updated their HIV treatment guidelines to recommend antiretroviral therapy (ART) for all people with HIV (PWH) regardless of CD4 count. We investigated recent trends and disparities in early receipt of ART prescription and subsequent viral suppression (VS). METHODS: We examined data from ART-naïve PWH newly presenting to HIV care at 13 North American AIDS Cohort Collaboration on Research and Design clinical cohorts in the United States during 2012-2018. We calculated the cumulative incidence of early ART (within 30 days of entry into care) and early VS (within 6 months of ART initiation) using the Kaplan-Meier survival function. Discrete time-to-event models were fit to estimate unadjusted and adjusted associations of early ART and VS with sociodemographic and clinical factors. RESULTS: Among 11 853 eligible ART-naïve PWH, the cumulative incidence of early ART increased from 42% in 2012 to 82% in 2018. The cumulative incidence of early VS among the 8613 PWH who initiated ART increased from 83% in 2012 to 93% in 2018. In multivariable models, factors independently associated with delayed ART and VS included non-Hispanic/Latino Black race, residence in the South census region, being a male with injection drug use acquisition risk, and history of substance use disorder (SUD; all P ≤ .05). CONCLUSIONS: Early ART initiation and VS have substantially improved in the United States since the release of universal treatment guidelines. Disparities by factors related to social determinants of health and SUD demand focused attention on and services for some subpopulations.

BACKGROUND: Adolescents living with HIV (ALHIV) experience higher mortality and are more likely to have poor antiretroviral therapy (ART) adherence and unsuppressed viral load (VL) compared to adults. Enhanced adherence counseling (EAC) is a client-centered counseling strategy that aims to identify and address barriers to optimal ART use and can be tailored to the unique needs of adolescents. This study aimed to better understand adherence barriers among ALHIV with suspected treatment failure and their experience with EAC to inform future programming. METHODS: A qualitative study was conducted in Homa Bay and Turkana counties, Kenya in 2019 with adolescents and caregivers of children and adolescents living with HIV with suspected treatment failure after 6months on ART and who had received 1 EAC sessions. Sixteen focus group discussions (FGDs) were conducted; five FGDs each were held with adolescents 12-14years (n=48) and 15-19years (n=36). Caregivers (n=52) participated in six FGDs. Additionally, 17 healthcare workers providing pediatric/adolescent HIV services participated in in-depth interviews. Audio recordings were transcribed and translated from Kiswahili or Dholuo into English and coded using MAXQDA software. Data were thematically analyzed by participant group. RESULTS: Participants identified adolescents' fear of being stigmatized due to their HIV status and their relationship with and level of support provided by caregivers. This underpinned and often undermined adolescents' ART-taking behavior and progress towards more independent medication management. Adolescents were generally satisfied with EAC and perceived it to be important in improving adherence and reducing VL. However, problems were noted with facility-based, individual EAC counseling, including judgmental attitudes of providers and difficulties traveling to and keeping EAC clinic appointments. Participant-suggested improvements to EAC included peer support groups in addition to individual counseling, allowing for greater flexibility in the timing and location of sessions and greater caregiver involvement. CONCLUSIONS: The findings provide opportunities to better tailor EAC interventions to promote improved ALHIV adherence and caregiver-supported disease management. Multi-prong EAC interventions that include peer-led and community approaches and target adolescent and caregiver treatment literacy may improve EAC delivery, address issues contributing to poor adherence, and position adolescents to achieve viral suppression. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04915469.

BACKGROUND: Beginning in March 2021, Mexico vaccinated childcare workers with a single-dose CanSino Biologics (Adv5-nCoV) COVID-19 vaccine. Although CanSino is currently approved for use in 10 Latin American, Asian, and European countries, little information is available about its vaccine effectiveness (VE). METHODS: We evaluated CanSino VE within a childcare worker cohort that included 1,408 childcare facilities. Participants were followed during March-December 2021 and tested through SARS-CoV-2 RT-PCR or rapid antigen test if they developed any symptom compatible with COVID-19. Vaccination status was obtained through worker registries. VE was calculated as 100% × (1-hazard ratio for SARS-CoV-2 infection in fully vaccinated vs. unvaccinated participants), using an Andersen-Gill model adjusted for age, sex, state, and local viral circulation. RESULTS: The cohort included 43,925 persons who were mostly (96%) female with a median age of 32 years; 37,646 (86%) were vaccinated with CanSino. During March-December 2021, 2,250 (5%) participants had laboratory-confirmed COVID-19, of whom 25 were hospitalized and 6 died. Adjusted VE was 20% (95% CI = 10-29%) against illness, 76% (42-90%) against hospitalization, and 94% (66-99%) against death. VE against illness declined from 48% (95% CI = 33-61) after 14-60 days following full vaccination to 20% (95% CI = 9-31) after 61-120 days. CONCLUSIONS: CanSino vaccine was effective at preventing COVID-19 illness and highly effective at preventing hospitalization and death. It will be useful to further evaluate duration of protection and assess the value of booster doses to prevent COVID-19 and severe outcomes.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

To the Editor.We read with concern the manuscript by Gill et al1 that described autopsy findings for 2 adolescents who died after COVID-19 vaccination. The authors correctly stated that the Centers for Disease Control and Prevention (CDC) performed testing for SARS-CoV-2 and found no evidence of SARS-CoV-2 infection in autopsy tissues from the decedents. However, the authors did not include findings from far more thorough immunohistochemical and molecular testing performed by the CDC for each patient. We believe that all of the CDC's findings should be considered carefully, and that the omission of these data has important implications for the conclusions of this paper.

There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with human immunodeficiency virus (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCL) in the modern antiretroviral therapy (ART) era. NA-ACCORD and COMPLETE are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study 52, 64, 101, 500 and 246 PWH with histological confirmation of TCL, primary CNS, Burkitt's, diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL) respectively and 450 TCL without HIV were eligible for analysis. At the time of TCL diagnosis, Anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. While PWH with TCL diagnosed between 1996-2009, experienced a low 5-year survival probability at 0.23 (95% CI: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010-2016 (0.69; 95% CI: 0.48, 1; p=0.04) in contrast to TCL among PWoH (0.45; 95% CI: 0.41, 0.51; p=0.53). Similarly, PWH with ALCL diagnosed between 1996-2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt's (0.43; 95% CI:0.33, 0.57; p=0.09) and DLBCL (0.17; 95% CI: 0.06, 0.46; p=0.11) and behind HL (0.57; 95% CI: 0.50, 0.65; p <0.0001). Despite a small number, those diagnosed between 2010-2016, experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison to PWoH (0.76; 95% CI: 0.66, 0.87; p=0.58). Thus, our analysis confirms improved overall survival for aggressive B and T-cell malignancies among PWH in the last decade.

BACKGROUND: Integrase strand transfer inhibitor (InSTI)-based regimens have been recommended as first-line antiretroviral therapy (ART) for adults with HIV. But data on long-term effects of InSTI-based regimens on virologic outcomes remain limited. Here we examined whether InSTI improved long-term virologic outcomes compared with efavirenz (EFV). METHODS: We included adults from the North American AIDS Cohort Collaboration on Research and Design who initiated their first ART regimen containing either InSTI or EFV between 2009 and 2016. We estimated differences in the proportion virologically suppressed up to 7 years of follow-up in observational intention-to-treat and per-protocol analyses. RESULTS: Of 15 318 participants, 5519 (36%) initiated an InSTI-based regimen and 9799 (64%) initiated the EFV-based regimen. In observational intention-to-treat analysis, 81.3% of patients in the InSTI group and 67.3% in the EFV group experienced virologic suppression at 3 months after ART initiation, corresponding to a difference of 14.0% (95% CI 12.4-15.6). At 1 year after ART initiation, the proportion virologically suppressed was 89.5% in the InSTI group and 90.2% in the EFV group, corresponding to a difference of -0.7% (95% CI -2.1 to 0.8). At 7 years, the proportion virologically suppressed was 94.5% in the InSTI group and 92.5% in the EFV group, corresponding to a difference of 2.0% (95% CI -7.3 to 11.3). The observational per-protocol results were similar to intention-to-treat analyses. CONCLUSIONS: Although InSTI-based initial ART regimens had more rapid virologic response than EFV-based regimens, the long-term virologic effect was similar. Our findings may inform guidelines regarding preferred initial regimens for HIV treatment.

INTRODUCTION: Because of low pediatric HIV prevalence, more tests are needed to find 1 HIV-positive child compared with adults. In Uganda, the number needed to test (NNT) to find 1 new HIV-positive child was 64 in outpatient departments (OPDs) and 31 through index testing. We aimed to develop and validate a pediatric (1.5-14 years) screening tool to optimize testing approaches. METHODS: Phase 1 evaluated the performance of 10 screening questions in 14 OPDs using a variable selection algorithm to evaluate combinations of screening questions. Using logistic regression, we identified the number of screening questions with the best predictive accuracy using the receiver operation characteristic curve. Phase 2 validated the proposed tool in 15 OPDs and 7 orphan and vulnerable children programs. We estimated sensitivity, specificity, and NNT accounting for intercluster correlations. RESULTS: A total of 3482 children were enrolled. The optimal model included reported HIV-positive maternal status or 2/5 symptoms (sickly in the last 3 months, recurring skin problems, weight loss, not growing well, and history of tuberculosis). The proposed tool had sensitivity of 83.6% [95% confidence interval (CI): 68.1 to 92.4] and specificity of 62.5% (95% CI: 55.0 to 69.4). The tool was validated in a sample of 11,342 children; sensitivity was 87.8% (95% CI: 80.9 to 92.5) and specificity 62.6% (95% CI: 54.8 to 69.7) across OPDs and community sites. In OPDs, sensitivity was 88.1% (95% CI: 80.8 to 92.8) and specificity 69.0% (95% CI: 61.9 to 75.3). The NNT was 43 (95% CI: 28 to 67) across settings and 28 (95% CI: 20 to 38) for OPD. CONCLUSIONS: This HIV screening tool has high sensitivity and reasonable specificity, increasing testing efficiency and yield for children and adolescents.

Two outbreaks of Shiga toxin-producing Escherichia coli O121:H19 associated with wheat flour, in the United States of America and Canada, involved strains with an unusual phenotype, delayed lactose utilization (DLU). These strains do not ferment lactose when initially cultured on MacConkey agar (MAC), but lactose fermentation occurs following subculture to a second plate of MAC. The prevalence of DLU was determined by examining the -galactosidase activity of 49 strains of E. coli O121, and of 37 other strains of E. coli. Twenty four of forty three O121:H19 and one O121:NM displayed DLU. Two strains (O121:NM and O145:H34) did not have detectable -galactosidase activity. -glucuronidase activity of O121 strains was also determined. All but six DLU strains had normal -glucuronidase activity. -glucuronidase activity was suppressed on MAC for 17 of 23 O121 non-DLU strains. Genomic analysis found that DLU strains possessed an insertion sequence, IS600 (1267 bp), between lacZ (-galactosidase) and lacY (-galactoside permease), that was not present in strains exhibiting normal lactose utilization. The insert might reduce the expression of -galactoside permease, delaying import of lactose, resulting in the DLU phenotype. The high probability of DLU should be considered when using lactose-containing media for the isolation of STEC O121. 2021

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. METHODS: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. RESULTS: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). CONCLUSIONS: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.

BACKGROUND: Understanding advances in the care and treatment of adults with HIV as well as remaining gaps requires comparing differences in mortality between persons entering care for HIV and the general population. OBJECTIVE: To assess the extent to which mortality among persons entering HIV care in the United States is elevated over mortality among matched persons in the general U.S. population and trends in this difference over time. DESIGN: Observational cohort study. SETTING: Thirteen sites from the U.S. North American AIDS Cohort Collaboration on Research and Design. PARTICIPANTS: 82 766 adults entering HIV clinical care between 1999 and 2017 and a subset of the U.S. population matched on calendar time, age, sex, race/ethnicity, and county using U.S. mortality and population data compiled by the National Center for Health Statistics. MEASUREMENTS: Five-year all-cause mortality, estimated using the Kaplan-Meier estimator of the survival function. RESULTS: Overall 5-year mortality among persons entering HIV care was 10.6%, and mortality among the matched U.S. population was 2.9%, for a difference of 7.7 (95% CI, 7.4 to 7.9) percentage points. This difference decreased over time, from 11.1 percentage points among those entering care between 1999 and 2004 to 2.7 percentage points among those entering care between 2011 and 2017. LIMITATION: Matching on available covariates may have failed to account for differences in mortality that were due to sociodemographic factors rather than consequences of HIV infection and other modifiable factors. CONCLUSION: Mortality among persons entering HIV care decreased dramatically between 1999 and 2017, although those entering care remained at modestly higher risk for death in the years after starting care than comparable persons in the general U.S. population. PRIMARY FUNDING SOURCE: National Institutes of Health.

BACKGROUND: The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole genome sequencing (WGS) across two CDC Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community and healthcare-associated disease and assess transmission. METHODS: C. difficile isolates from CDI cases over three months between 2016 and 2017 underwent WGS. Cases were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. Cases were epidemiologically classified as healthcare (HCA) or community (CA) associated. RESULTS: Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were ST42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%), and ST41 (77.8%). ST1 was more frequent in NY than MN (10.8% vs 3.1%). Thirty three pairs were closely related genomically, 14 of which had potential patient-patient transmission supported by chart review. DISCUSSION: The genomic epidemiology of C. difficile across two regions of the US indicates the presence of a diverse strain profile and limited direct transmission.

Certain communities in the United States experience greater opioid-involved overdose mortality than others. Interventions to stem overdose benefit from contextual understandings of communities' needs and strengths in addressing the opioid crisis. This project aims to understand multiple stakeholder perspectives on the opioid epidemic in communities disproportionately affected by opioid-involved overdose mortality. Methods: We performed a rapid-cycle qualitative assessment study utilizing in-depth interviews with community stakeholders and observations of community meetings in eight communities in Allegheny County, Pennsylvania, USA, disproportionately impacted by opioid-involved overdose mortality. Stakeholder categories included: current and past illicit users of opioids; medical and social service providers; emergency medical services; law enforcement; spouse or other family members of illicit users/former users of opioids; government officials; school officials; community members. Content analysis was utilized to identify themes and answer study questions. Regular feedback to stakeholders was provided to support targeted interventions. Results: We performed semi-structured, in-depth interviews with 130 community stakeholders and 29 community meeting observations in 2018-2019. Participants perceived similar economic and social determinants as origins of the opioid overdose epidemic including lack of economic resources, loss of jobs, transient populations and dilapidated housing. However, they differed in their awareness of and attention to the epidemic. Awareness was dependent on the visibility of opioid use (presence of paraphernalia litter, location of drug users, media coverage, and relationship to users). Overall, there was good knowledge of naloxone for opioid overdose reversal but less knowledge about local syringe services programs. Perceptions of harm reduction efforts were ambivalent. Conclusions: Members of communities impacted by the opioid epidemic perceived that economic downturn was a major factor in the opioid overdose epidemic. However, the varied beliefs within and between communities suggest that interventions need to be tailored according to the cultural norms of place.

IMPORTANCE: People with HIV (PWH) are often coinfected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), leading to increased risk of developing hepatocellular carcinoma (HCC), but few cohort studies have had sufficient power to describe the trends of HCC incidence and risk among PWH in the combination antiretroviral therapy (cART) era. OBJECTIVE: To determine the temporal trends of HCC incidence rates (IRs) and to compare rates by risk factors among PWH in the cART era. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) study, which was conducted between 1996 and 2015. NA-ACCORD pooled individual-level data from 22 HIV clinical and interval cohorts of PWH in the US and Canada. PWH aged 18 years or older with available CD4 cell counts and HIV RNA data were enrolled. Data analyses were completed in March 2020. EXPOSURES: HBV infection was defined as detection of either HBV surface antigen, HBV e antigen, or HBV DNA in serum or plasma any time during observation. HCV infection was defined by detection of anti-HCV seropositivity, HCV RNA, or detectable genotype in serum or plasma at any time under observation. MAIN OUTCOMES AND MEASURES: HCC diagnoses were identified on the basis of review of medical records or cancer registry linkage. RESULTS: Of 10 283 PWH with 723 441 person-years of follow-up, the median (interquartile range) age at baseline was 43 (36-51) years, 93 017 (85.1%) were male, 44 752 (40.9%) were White, 44 322 (40.6%) were Black, 21 343 (19.5%) had HCV coinfection, 6348 (5.8%) had HBV coinfection, and 2082 (1.9%) had triple infection; 451 individuals received a diagnosis of HCC by 2015. Between the early (1996-2000) and modern (2006-2015) cART eras, the crude HCC IR increased from 0.28 to 0.75 case per 1000 person-years. HCC IRs remained constant among HIV-monoinfected persons or those coinfected with HBV, but from 1996 to 2015, IRs increased among PWH coinfected with HCV (from 0.34 cases/1000 person-years in 1996 to 2.39 cases/1000 person-years in 2015) or those with triple infection (from 0.65 cases/1000 person-years in 1996 to 4.49 cases/1000 person-years in 2015). Recent HIV RNA levels greater than or equal to 500 copies/mL (IR ratio, 1.8; 95% CI, 1.4-2.4) and CD4 cell counts less than or equal to 500 cells/μL (IR ratio, 1.3; 95% CI, 1.0-1.6) were associated with higher HCC risk in the modern cART era. People who injected drugs had higher HCC risk compared with men who had sex with men (IR ratio, 2.0; 95% CI, 1.3-2.9), adjusted for HBV-HCV coinfection. CONCLUSIONS AND RELEVANCE: HCC rates among PWH increased significantly over time from 1996 to 2015. PWH coinfected with viral hepatitis, those with higher HIV RNA levels or lower CD4 cell counts, and those who inject drugs had higher HCC risk.

BACKGROUND: Studies suggest lower risk of breast cancer in women with versus without HIV. These estimates may be biased by lower life expectancy and younger age distribution of women with HIV. Our analysis evaluated this bias and characterized secular trends in breast cancer among women with HIV initiating ART. We hypothesized breast cancer risk would increase over time as mortality decreased. SETTING: Women with HIV prescribed ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1997-2016. METHODS: We estimated breast cancer hazard (cause-specific hazard ratios [csHR]) and cumulative incidence accounting for competing risks (subdistribution hazard ratios [sdHR]) to assess changes in breast cancer risk over time. This was assessed overall (1997-2016) and within/across calendar periods. Analyses were adjusted for race/ethnicity and inverse probability weighted for cohort. Cumulative incidence was graphically assessed by calendar period and race/ethnicity. RESULTS: We observed 11,587 women during 1997-2016, contributing 63 incident breast cancer diagnoses and 1,353 deaths (73,445 person-years [median follow-up=4.5 years]). Breast cancer cumulative incidence was 3.2% for 1997-2016. We observed no secular trends in breast cancer hazard or cumulative incidence. There were annual declines in the hazard and cumulative incidence of death (csHR and sdHR: 0.89, 95% CI 0.87, 0.91) which remained within and across calendar periods. CONCLUSION: These findings contradict the hypothesis of increasing breast cancer risk with declining mortality over time among women with HIV, suggesting limited impact of changing mortality on breast cancer risk. Additional inquiry is merited as survival improves among women with HIV.

BACKGROUND: Persons with HIV (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk. METHODS: In six US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (Years 2-5) and long-term (Years 6-11) suppression and lowest pre-suppression CD4 count <200 and ≥200 cells/µL, Poisson regression models estimated hospitalization incidence rate ratios (aIRR) comparing patients by time-updated CD4 count category, adjusted for cohort, age, gender, calendar year, suppression duration, and lowest pre-suppression CD4 count. RESULTS: The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% White. Among patients with lowest pre-suppression CD4 <200 cells/μL (44%), patients with current CD4 200-350 versus >500 cells/μL had an aIRR of 1.44 during early suppression (95% CI 1.01-2.06), and 1.67 (1.03-2.72) during long-term suppression. Among patients with lowest pre-suppression CD4 ≥200 (56%), patients with current CD4 351-500 versus >500 cells/μL had an aIRR of 1.22 (0.93-1.60) during early suppression and 2.09 (1.18-3.70) during long-term suppression. CONCLUSIONS: Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates, and could potentially benefit from targeted clinical management strategies.

From 2005 to 2018, among 32013 adults entering HIV care in the US, median time to ART prescription declined from 69 to 6 days, median CD4 count at entry into care increased from 300 to 362 cells/µL, and median CD4 count at ART prescription increased from 160 to 364 cells/µL.