Invasive fungal infections are rare in pediatric and young adult autologous hematopoietic stem cell transplant patients.

BACKGROUND: Pediatric and young adult patients undergoing autologous hematopoietic stem cell transplant (auto-HSCT) face a crucial, yet understudied, risk of invasive fungal infections (IFI), especially compared to allogeneic transplants. This gap underscores the need for research in pediatric patients undergoing auto-HSCT. Our objective was to evaluate the incidence of IFI in pediatric and young adult patients during the first year after auto-HSCT. MATERIALS AND METHODS: We conducted a single-center retrospective analysis of 150 pediatric and young adult auto-HSCT patients who underwent transplant from January 2013 to January 2023. We focused on IFI incidence within the first-year post transplant, using the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria for IFI identification. RESULTS: Among the 150 patients analyzed, with 240 unique transplant episodes, the primary indication was neuroblastoma (37.3%), and micafungin was extensively used for prophylaxis (82.7%). There was an absence of IFI from yeast and mold species, suggesting a low IFI risk in this cohort. The incidence of IFI in pediatric auto-HSCT recipients receiving micafungin primary antifungal prophylaxis is rare. CONCLUSIONS: The findings advocate for further research to refine prophylaxis guidelines and highlight the need for individualized risk assessment to optimize post-transplant care.

Treatment Access among Younger Medicaid Beneficiaries with Multiple Myeloma.

PURPOSE: Continuous Medicaid coverage prior to a cancer diagnosis has been associated with earlier detection and better outcomes, for patients with solid tumors. In this study, we aimed to determine if this was observed among patients with multiple myeloma, a hematologic cancer where there are no routine screening tests and most are diagnosed through acute medical events. MATERIALS AND METHODS: This is an analysis of the Merative MarketScan Multistate Medicaid Database, a claims-based dataset. In total, 1105 patients < 65 years old were included in the analyses. Among them, 66% had continuous enrollment (at least 6 months enrollment prior to myeloma), and 34% had discontinuous enrollment (2-6 months enrollment prior to myeloma). Multivariable Cox regression was used to estimate the association between continuous enrollment status and receipt of myeloma treatment within 1 year of index date. RESULTS: Only 54% of all Medicaid enrollees received myeloma therapy and only 12% received stem cell transplant within the 1st year. Those with continuous enrollment were less likely to receive any treatment (adjusted hazard ratio [aHR] 0.59; 95% confidence interval [CI] 0.59-0.70; P < .001) and to receive stem cell transplant (aHR 0.51; 95% CI 0.32-0.81; P = .005). CONCLUSION: Patients with continuous Medicaid coverage prior to diagnosis were less likely to receive myeloma therapy. Future studies should examine whether myeloma patients with continuous Medicaid enrollment have more chronic financial instability and/or higher medical needs and, thus, have higher barriers to care.

Asymptomatic Incidence of Monoclonal Gammopathy of Undetermined Significance and Preclinical Duration to Myeloma Diagnosis: A Modeling Study.

Background Monoclonal gammopathy of undetermined significance (MGUS) is the premalignant condition of multiple myeloma (MM). Given a lack of population-based screening for MGUS and its asymptomatic nature, the epidemiology of MGUS remains unknown. This study estimated age- and race/ethnicity-specific MGUS incidence and preclinical duration from MGUS to MM in the United States. Methods A previously published modeling approach was used to calculate national MGUS incidence using estimates of MGUS prevalence, MM incidence, MM-specific and all-cause mortality, and population age distribution from the National Health and Nutrition Examination Survey, 1999-2004, and Surveillance, Epidemiology, and End Results, 2000-2021. The estimated MGUS prevalence was divided by MGUS incidence to obtain preclinical duration of MM. Results MGUS incidence for non-Hispanic white (NHW) populations was 52, 86, 142, and 181 and for non-Hispanic black (NHB) population was 110, 212, 392, and 570 per 100,000 person-years at ages 50, 60, 70, and 80, respectively. The average preclinical duration was 20.5 (95% confidence interval, CI: 16.5, 26.1) years for the NHW population and 14.2 (95% CI: 11.5, 17.6) years for the NHB population. The cumulative risk of developing MGUS in age 50-85 was 2.8% (95% CI: 1.7%, 4.2%) for the NHW population and 6.1% (95% CI: 3.8%, 10.0%) for the NHB population. Conclusion NHB populations had a higher MGUS incidence rate at all ages and a shorter preclinical duration of MM compared to their NHW counterparts. Impact This study provides insights into the epidemiology of MGUS and enhances our understanding of the natural history of MM.

Trajectory of Sleep, Depression, and Quality of Life in Pediatric HSCT Recipients.

Disrupted sleep is commonly reported during hematopoietic stem cell transplant. In this study, we use actigraphy to measure sleep parameters, and qualitative measures of quality of life, depression, and sleep in pediatric and young adult transplant recipients to describe their time course through transplant. Eight patients had evaluable actigraphy data, and 10 patients completed the surveys. The median age of the 6 male and 7 female participants was 13.94 years old. Sleep duration and efficiency measured by actigraphy were suboptimal prior to transplant, then declined to a nadir between Day +7 to +14. Self-reported sleep quality, depression, and quality of life were worst at Day +14 to +30 but improved by Day +100. Findings support efforts to improve sleep, which may improve recovery, mental health and quality of life.

Estimating the health effects of COVID-19-related immunisation disruptions in 112 countries during 2020-30: a modelling study.

BACKGROUND: There have been declines in global immunisation coverage due to the COVID-19 pandemic. Recovery has begun but is geographically variable. This disruption has led to under-immunised cohorts and interrupted progress in reducing vaccine-preventable disease burden. There have, so far, been few studies of the effects of coverage disruption on vaccine effects. We aimed to quantify the effects of vaccine-coverage disruption on routine and campaign immunisation services, identify cohorts and regions that could particularly benefit from catch-up activities, and establish if losses in effect could be recovered. METHODS: For this modelling study, we used modelling groups from the Vaccine Impact Modelling Consortium from 112 low-income and middle-income countries to estimate vaccine effect for 14 pathogens. One set of modelling estimates used vaccine-coverage data from 1937 to 2021 for a subset of vaccine-preventable, outbreak-prone or priority diseases (ie, measles, rubella, hepatitis B, human papillomavirus [HPV], meningitis A, and yellow fever) to examine mitigation measures, hereafter referred to as recovery runs. The second set of estimates were conducted with vaccine-coverage data from 1937 to 2020, used to calculate effect ratios (ie, the burden averted per dose) for all 14 included vaccines and diseases, hereafter referred to as full runs. Both runs were modelled from Jan 1, 2000, to Dec 31, 2100. Countries were included if they were in the Gavi, the Vaccine Alliance portfolio; had notable burden; or had notable strategic vaccination activities. These countries represented the majority of global vaccine-preventable disease burden. Vaccine coverage was informed by historical estimates from WHO-UNICEF Estimates of National Immunization Coverage and the immunisation repository of WHO for data up to and including 2021. From 2022 onwards, we estimated coverage on the basis of guidance about campaign frequency, non-linear assumptions about the recovery of routine immunisation to pre-disruption magnitude, and 2030 endpoints informed by the WHO Immunization Agenda 2030 aims and expert consultation. We examined three main scenarios: no disruption, baseline recovery, and baseline recovery and catch-up. FINDINGS: We estimated that disruption to measles, rubella, HPV, hepatitis B, meningitis A, and yellow fever vaccination could lead to 49 119 additional deaths (95% credible interval [CrI] 17 248-134 941) during calendar years 2020-30, largely due to measles. For years of vaccination 2020-30 for all 14 pathogens, disruption could lead to a 2·66% (95% CrI 2·52-2·81) reduction in long-term effect from 37 378 194 deaths averted (34 450 249-40 241 202) to 36 410 559 deaths averted (33 515 397-39 241 799). We estimated that catch-up activities could avert 78·9% (40·4-151·4) of excess deaths between calendar years 2023 and 2030 (ie, 18 900 [7037-60 223] of 25 356 [9859-75 073]). INTERPRETATION: Our results highlight the importance of the timing of catch-up activities, considering estimated burden to improve vaccine coverage in affected cohorts. We estimated that mitigation measures for measles and yellow fever were particularly effective at reducing excess burden in the short term. Additionally, the high long-term effect of HPV vaccine as an important cervical-cancer prevention tool warrants continued immunisation efforts after disruption. FUNDING: The Vaccine Impact Modelling Consortium, funded by Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation. TRANSLATIONS: For the Arabic, Chinese, French, Portguese and Spanish translations of the abstract see Supplementary Materials section.

The Chalcidoidea bush of life: evolutionary history of a massive radiation of minute wasps.

Chalcidoidea are mostly parasitoid wasps that include as many as 500 000 estimated species. Capturing phylogenetic signal from such a massive radiation can be daunting. Chalcidoidea is an excellent example of a hyperdiverse group that has remained recalcitrant to phylogenetic resolution. We combined 1007 exons obtained with Anchored Hybrid Enrichment with 1048 ultra-conserved elements (UCEs) for 433 taxa including all extant families, >95% of all subfamilies, and 356 genera chosen to represent the vast diversity of the superfamily. Going back and forth between the molecular results and our collective knowledge of morphology and biology, we detected bias in the analyses that was driven by the saturation of nucleotide data. Our final results are based on a concatenated analysis of the least saturated exons and UCE datasets (2054 loci, 284 106 sites). Our analyses support an expected sister relationship with Mymarommatoidea. Seven previously recognized families were not monophyletic, so support for a new classification is discussed. Natural history in some cases would appear to be more informative than morphology, as illustrated by the elucidation of a clade of plant gall associates and a clade of taxa with planidial first-instar larvae. The phylogeny suggests a transition from smaller soft-bodied wasps to larger and more heavily sclerotized wasps, with egg parasitism as potentially ancestral for the entire superfamily. Deep divergences in Chalcidoidea coincide with an increase in insect families in the fossil record, and an early shift to phytophagy corresponds with the beginning of the "Angiosperm Terrestrial Revolution". Our dating analyses suggest a middle Jurassic origin of 174 Ma (167.3-180.5 Ma) and a crown age of 162.2 Ma (153.9-169.8 Ma) for Chalcidoidea. During the Cretaceous, Chalcidoidea may have undergone a rapid radiation in southern Gondwana with subsequent dispersals to the Northern Hemisphere. This scenario is discussed with regard to knowledge about the host taxa of chalcid wasps, their fossil record and Earth's palaeogeographic history.

Understanding Stakeholder Dissemination Preferences for an Agriculture, Forestry, and Fishing Injury Surveillance System.

Researchers and epidemiologists are working to improve the capture of agriculture, forestry, and fishing (AgFF) injuries in a variety of ways. A critical component of any surveillance system is the dissemination of information. The purpose of this paper is to report on a survey conducted with AgFF injury surveillance stakeholders to understand preferred dissemination strategies. The survey was distributed using REDCap via web link to organizational stakeholders, which included advisory board members, safety trainers, industry managers and workers, and research collaborators. In total, there were 75 respondents (21% response rate). Occupation and industry influenced preference in update methods. Regarding the length and breadth of updates, 63% of respondents prefer reports (one to five pages), followed by 57% desiring a summary (less than one page), while only 24% wanted a detailed analysis. Social media and news preferences were also different among stakeholders. Surveillance data were desired for 1) trend analysis, 2) tailoring activities and solutions for education, training, outreach and interventions and 3) for research purposes such as grant proposals and evaluation. The dissemination of injury surveillance data should be tailored to the intended audience. Greater attention needs to be paid to the ways in which we share our findings.

Disentangling age, gender, and racial/ethnic disparities in multiple myeloma burden: a modeling study.

Multiple myeloma (MM) is a hematological malignancy that is consistently preceded by an asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Disparities by age, gender, and race/ethnicity in both MGUS and MM are well-established. However, it remains unclear whether these disparities can be explained by increased incidence of MGUS and/or accelerated progression from MGUS to MM. Here, we fit a mathematical model to nationally representative data from the United States and showed that the difference in MM incidence can be explained by an increased incidence of MGUS among male and non-Hispanic Black populations. We did not find evidence showing differences in the rate of progression from MGUS to MM by either gender or race/ethnicity. Our results suggest that screening for MGUS among high-risk groups (e.g., non-Hispanic Black men) may hold promise as a strategy to reduce the burden and MM health disparities.

Does ignoring transmission dynamics lead to underestimation of the impact of interventions against mosquito-borne disease?

New vector-control technologies to fight mosquito-borne diseases are urgently needed, the adoption of which depends on efficacy estimates from large-scale cluster-randomised trials (CRTs). The release of Wolbachia-infected mosquitoes is one promising strategy to curb dengue virus (DENV) transmission, and a recent CRT reported impressive reductions in dengue incidence following the release of these mosquitoes. Such trials can be affected by multiple sources of bias, however. We used mathematical models of DENV transmission during a CRT of Wolbachia-infected mosquitoes to explore three such biases: human movement, mosquito movement and coupled transmission dynamics between trial arms. We show that failure to account for each of these biases would lead to underestimated efficacy, and that the majority of this underestimation is due to a heretofore unrecognised bias caused by transmission coupling. Taken together, our findings suggest that Wolbachia-infected mosquitoes could be even more promising than the recent CRT suggested. By emphasising the importance of accounting for transmission coupling between arms, which requires a mathematical model, we highlight the key role that models can play in interpreting and extrapolating the results from trials of vector control interventions.

Mortality in the US Populations With Monoclonal Gammopathy of Undetermined Significance.

This cohort study analyzes a nationally representative sample with a screening test for monoclonal gammopathy of undetermined significance (MGUS) to evaluate overall survival of populations with MGUS compared with those without MGUS among the general population in the US.

The morphological diversity of Mymaridae (Hymenoptera): an atlas of scanning electron micrographs. Part 1. General overview and structure of the head.

This is the first in a series of studies that aim to provide a comprehensive overview of the morphological diversity of Mymaridae (Hymenoptera), a monophyletic family of small parasitic wasps that are postulated as the sister group of other Chalcidoidea. The external cranial morphology of 65-75 genera and subgenera of Mymaridae (fairyflies) is described and illustrated with almost 430 scanning electron micrographs, including 73 micrographs of the anterior, 68 of the posterior, 75 of the dorsal, 75 of the lateral, and 67 of the ventral views of the head, plus 71 micrographs of the ventral view of the mouthparts. Twenty-one annotated figures illustrate the terms used for morphological structures. Two appendices list the 64 morphological terms and 5 measurements that are defined and illustrated, and the 116 currently recognized valid genera and subgenera of Mymaridae, including collection localities for those that are illustrated. Discussion of head morphology characteristic of Mymaridae is preceded by an overview that includes discussion of best practices for taxonomic descriptions and why these and accurate identifications require well preserved and imaged specimens. Aspects of intraspecific variation, colour, secondary sexual dimorphism, setation (chaetotaxy), surface sculpture and morphometrics are also treated as all of these are often important for describing and distinguishing species. Many of the features illustrated have not previously been used in Mymaridae systematics but may prove to be useful for helping to identify and describe genera and species.

Cell Therapy Informatics: Updates on the Integration of HCT/IEC Functionalities into an Electronic Medical Record System in the US to Promote Efficiency, Patient Safety, Research, and Data Interoperability.

The use of electronic health/medical record (EMR) systems has streamlined medical practice and improved efficiency of clinical care in recent years. However, EMR systems are not generally well designed to support research and tracking of longitudinal outcomes across populations, which are particularly important in hematopoietic stem cell transplantation (HCT) and immune effector cell therapy (IEC), where data reporting to registries and regulatory agencies are often required. Since its formation in 2014, the HCT EMR user group has worked with a large EMR vendor (Epic) to develop many functionalities within the EMR to improve the care of HCT/IEC patients and facilitate the capture of HCT/IEC data in an easily interoperable format. Awareness and the widespread adoption of these new tools among transplant centers remains a challenge, however. In this report, we aim to increase awareness and adoption of these new features in the Epic EMR across the transplantation community, advocate for the use of data standards, and promote future collaboration with other commercial EMRs to develop standardized HCT/IEC content to improve patient care and facilitate interoperable data exchange.

The Impact of Emerging Plasmodium knowlesi on Accurate Diagnosis by Light Microscopy: A Systematic Review and Modeling Analysis.

The five major Plasmodium spp. that cause human malaria appear similar under light microscopy, which raises the possibility that misdiagnosis could routinely occur in clinical settings. Assessing the extent of misdiagnosis is of particular importance for monitoring P. knowlesi, which cocirculates with the other Plasmodium spp. We performed a systematic review and meta-analysis of studies comparing the performance of microscopy and polymerase chain reaction (PCR) for diagnosing malaria in settings with co-circulation of the five Plasmodium spp. We assessed the extent to which co-circulation of Plasmodium parasites affects diagnostic outcomes. We fit a Bayesian hierarchical latent class model to estimate variation in microscopy sensitivity and specificity measured against PCR as the gold standard. Mean sensitivity of microscopy was low, yet highly variable across Plasmodium spp., ranging from 65.7% (95% confidence interval: 48.1-80.3%) for P. falciparum to 0.525% (95% confidence interval 0.0210-3.11%) for P. ovale. Observed PCR prevalence was positively correlated with estimated microscopic sensitivity and negatively correlated with estimated microscopic specificity, though the strength of the associations varied by species. Our analysis suggests that cocirculation of Plasmodium spp. undermines the accuracy of microscopy. Sensitivity was considerably lower for P. knowlesi, P. malariae, and P. ovale. The negative association between specificity and prevalence imply that less frequently encountered species may be misdiagnosed as more frequently encountered species. Together, these results suggest that the burden of P. knowlesi, P. malariae, and P. ovale may be underappreciated in a clinical setting.

The morphological diversity of Mymaridae (Hymenoptera): an atlas of scanning electron micrographs. Part 2. Structure of the mesosoma.

This is the second in a series of studies that aim to provide a comprehensive overview of the morphological diversity of Mymaridae (Hymenoptera) or fairyflies, a monophyletic family of small parasitic wasps postulated to be the sister group of all other Chalcidoidea. The external morphology of the mesosoma of about 6575 taxa, representing 5565% of the 115 currently valid described genera and subgenera, is described and illustrated with almost 269 scanning electron micrographs, including 77 micrographs of the dorsal, 71 micrographs of the lateral, 59 micrographs of the ventral, 53 micrographs of the anterior, and 9 micrographs of the posterior views of the mesosoma. Twenty annotated figures of the external and major internal structures are given. Two appendices list the morphological terms used, and names of the 75 genera and subgenera of Mymaridae illustrated. The variety of characters and their features that could be used to help define morphologically the genera, and possibly also the species, of Mymaridae is discussed.

Secondary Impact of the Coronavirus Disease 19 Pandemic on Patients and the Cellular Therapy Healthcare Ecosystem.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly impacted global health and healthcare delivery systems. To characterize the secondary effects of the COVID-19 pandemic and mitigation strategies used in the delivery of hematopoietic stem cell transplantation (HSCT) care, we performed a comprehensive literature search encompassing changes in specific donor collection, processing practices, patient outcomes, and patient-related concerns specific to HSCT and HSCT-related healthcare delivery. In this review, we summarize the available literature on the secondary impacts the COVID-19 pandemic on the fields of HSCT and cellular therapy. The COVID-19 pandemic has had numerous secondary impacts on patients undergoing HSCT and the healthcare delivery systems involved in providing complex care to HSCT recipients. Institutions must identify these influences on outcomes and adjust accordingly to maintain and improve outcomes for the transplantation and cellular therapy community.

Projecting vaccine demand and impact for emerging zoonotic pathogens.

BACKGROUND: Despite large outbreaks in humans seeming improbable for a number of zoonotic pathogens, several pose a concern due to their epidemiological characteristics and evolutionary potential. To enable effective responses to these pathogens in the event that they undergo future emergence, the Coalition for Epidemic Preparedness Innovations is advancing the development of vaccines for several pathogens prioritized by the World Health Organization. A major challenge in this pursuit is anticipating demand for a vaccine stockpile to support outbreak response. METHODS: We developed a modeling framework for outbreak response for emerging zoonoses under three reactive vaccination strategies to assess sustainable vaccine manufacturing needs, vaccine stockpile requirements, and the potential impact of the outbreak response. This framework incorporates geographically variable zoonotic spillover rates, human-to-human transmission, and the implementation of reactive vaccination campaigns in response to disease outbreaks. As proof of concept, we applied the framework to four priority pathogens: Lassa virus, Nipah virus, MERS coronavirus, and Rift Valley virus. RESULTS: Annual vaccine regimen requirements for a population-wide strategy ranged from > 670,000 (95% prediction interval 0-3,630,000) regimens for Lassa virus to 1,190,000 (95% PrI 0-8,480,000) regimens for Rift Valley fever virus, while the regimens required for ring vaccination or targeting healthcare workers (HCWs) were several orders of magnitude lower (between 1/25 and 1/700) than those required by a population-wide strategy. For each pathogen and vaccination strategy, reactive vaccination typically prevented fewer than 10% of cases, because of their presently low R0 values. Targeting HCWs had a higher per-regimen impact than population-wide vaccination. CONCLUSIONS: Our framework provides a flexible methodology for estimating vaccine stockpile needs and the geographic distribution of demand under a range of outbreak response scenarios. Uncertainties in our model estimates highlight several knowledge gaps that need to be addressed to target vulnerable populations more accurately. These include surveillance gaps that mask the true geographic distribution of each pathogen, details of key routes of spillover from animal reservoirs to humans, and the role of human-to-human transmission outside of healthcare settings. In addition, our estimates are based on the current epidemiology of each pathogen, but pathogen evolution could alter vaccine stockpile requirements.

Quality Improvement in Hematopoietic Stem Cell Transplant and Cellular Therapy: Using the Model for Improvement to impact Outcomes.

Quality improvement and quality assurance form a complementary and independent relationship. Quality assurance measures compliance against industry standards using audits, whereas quality improvement is a continuous process focused on processes and systems that can improve care. The Model for Improvement is a robust quality improvement tool that transplant and cellular therapy teams can use to redesign healthcare processes. The Model for Improvement uses several components addressed in sequence to organize and critically evaluate improvement activities. Unlike other health sciences clinical research, quality improvement projects, and research are based on dynamic hypotheses that develop into observable, serial tests of change with continuous collection and feedback of performance data to stakeholders.

Inferring person-to-person networks of Plasmodium falciparum transmission: are analyses of routine surveillance data up to the task?

BACKGROUND: Inference of person-to-person transmission networks using surveillance data is increasingly used to estimate spatiotemporal patterns of pathogen transmission. Several data types can be used to inform transmission network inferences, yet the sensitivity of those inferences to different data types is not routinely evaluated. METHODS: The influence of different combinations of spatial, temporal, and travel-history data on transmission network inferences for Plasmodium falciparum malaria were evaluated. RESULTS: The information content of these data types may be limited for inferring person-to-person transmission networks and may lead to an overestimate of transmission. Only when outbreaks were temporally focal or travel histories were accurate was the algorithm able to accurately estimate the reproduction number under control, Rc. Applying this approach to data from Eswatini indicated that inferences of Rc and spatiotemporal patterns therein depend upon the choice of data types and assumptions about travel-history data. CONCLUSIONS: These results suggest that transmission network inferences made with routine malaria surveillance data should be interpreted with caution.

A Medication Adherence Promotion System to Reduce Late Kidney Allograft Rejection: A Quality Improvement Study.

RATIONALE & OBJECTIVE: Adolescent and young adult kidney transplant recipients have a high risk of rejection related to suboptimal adherence. Multicomponent interventions improve adherence in controlled trials, but clinical implementation is lacking. We describe an initiative to reduce allograft rejection using evidence-based adherence promotion strategies. STUDY DESIGN: Interrupted time series. SETTING & PARTICIPANTS: Kidney transplant recipients cared for at Cincinnati Children's Hospital ≥ 1 year after transplant and taking ≥1 immunosuppressive medication(s) from 2014 through 2017. QUALITY IMPROVEMENT ACTIVITIES: The following interventions, collectively called MAPS (Medication Adherence Promotion System), were implemented over 14 months: (1) adherence promotion training for clinical staff, 2) electronic health record-supported adherence risk screening, (3) systematic assessment of medication adherence barriers, (4) designation of specific staff to address adherence barriers, (5) shared decision-making with the patients to overcome adherence barriers, (6) follow-up evaluation to assess progress, and (7) optional electronic medication monitoring. OUTCOMES: Primary Outcome: Late acute rejection. Process measures were conducted to assess barriers, identify barriers, and perform interventions. The secondary outcomes/balancing measures were de novo donor-specific antibodies (DSA), biopsy rate, and rejections per biopsy. ANALYTICAL APPROACH: Time series analysis using statistical process control evaluated patient-days between acute rejections as well as monthly rejections per 100 patient-months before and after implementation. To control for known rejection risk factors including changes in treatment and case mix, multivariable analyses were performed. RESULTS: The monthly rejection rate fell from 1.61 rejections per 100 patient-months in the 26 months before implementation to 0.88 rejections per 100 patient-months in the 22 months after implementation. In the multivariable analysis, MAPS was associated with a 50% reduction in rejection incidence (incidence rate ratio, 0.50 [95% CI, 0.27-0.91]; P = 0.02). DSA and time since transplant (per each additional year) were also associated with rejection incidence (incidence rate ratio, 2.27 [P = 0.02] and 0.87 [P = 0.02], respectively). LIMITATIONS: Single-center study, and potential confounding by unmeasured variables. CONCLUSIONS: Clinical implementation of evidence-based adherence-promotion strategies was associated with a 50% reduction in acute rejection incidence over 2 years.