Development and Diagnostic Potential of a Novel Bartonella henselae-Specific Immunoglobulin.

Bartonella henselae is a gram-negative rod-shaped bacterium and is the primary causative agent of Cat Scratch Disease (CSD). Although the prevalence of CSD is low in the human population, the possibility of developing multi-organ complications, especially in vulnerable individuals, remains a serious cause for concern. The immunofluorescent assay (IFA) is currently one of the most common laboratory tests for the detection of antibodies to B. henselae in serum, however, it has several disadvantages. The enzyme-linked immunosorbent assay (ELISA) technique offers a more quantitative, sensitive, and cost-effective alternative to conventional IFAs. Here, we report the purification of a novel bioidentical polyclonal antibody from discarded human serum for use as a standard in ELISAs against B. henselae. This novel method of antibody production overcomes the many limitations of animal-derived antibodies while also offering a more robust, reproducible, and scalable antibody production alternative for the diagnosis of CSD.

An Evaluation of Dose-Related HPV Vaccine Effectiveness Using Central Registries in Michigan.

BACKGROUND: Human papillomavirus (HPV) vaccine effectiveness (VE) evaluations provide important information for vaccination programs. We established a linkage between statewide central registries in Michigan to estimate HPV VE against in situ and invasive cervical lesions (CIN3+). METHODS: We linked females in Michigan's immunization and cancer registries using birth records to establish a cohort of 773,193 women with known vaccination history, of whom 3,838 were diagnosed with CIN3+. Residential address histories from a stratified random sample were used to establish a subcohort of 1,374 women without CIN3+ and 2,900 with CIN3+ among continuous Michigan residents. VE and 95% confidence intervals (CI) were estimated using cohort and case-cohort methods for up-to-date (UTD) vaccination and incomplete vaccination with 1 and 2 doses, and stratified by age at vaccination. RESULTS: Both analytic approaches demonstrated lower CIN3+ risk with UTD and non-UTD vaccination vs. no vaccination. The cohort analysis yielded VE estimates of 66% (95% CI, 60%-71%) for UTD, 33% (95% CI, 18%-46%) for 2 doses-not UTD, and 40% (95% CI, 27%-50%) for 1 dose. The case-cohort analysis yielded VE estimates of 72% (95% CI, 64%-79%) for UTD, 39% (95% CI, 10%-58%) for 2 doses-not UTD, and 48% (95% CI, 25%-63%) for 1 dose. VE was higher for vaccination at age <20 than ≥20 years. CONCLUSIONS: The statewide registry linkage found significant VE against CIN3+ with incomplete HPV vaccination, and an even higher VE with UTD vaccination. IMPACT: Future VE evaluations by number of doses for women vaccinated at younger ages may further clarify dose-related effectiveness.

Vaccine Coverage Across the Life Course in Michigan During the COVID-19 Pandemic: January‒September 2020.

Objectives. To assess the impact of the COVID-19 pandemic on immunization services across the life course. Methods. In this retrospective study, we used Michigan immunization registry data from 2018 through September 2020 to assess the number of vaccine doses administered, number of sites providing immunization services to the Vaccines for Children population, provider location types that administer adult vaccines, and vaccination coverage for children. Results. Of 12 004 384 individual vaccine doses assessed, 48.6%, 15.6%, and 35.8% were administered to children (aged 0-8 years), adolescents (aged 9-18 years), and adults (aged 19‒105 years), respectively. Doses administered overall decreased beginning in February 2020, with peak declines observed in April 2020 (63.3%). Overall decreases in adult doses were observed in all settings except obstetrics and gynecology provider offices and pharmacies. Local health departments reported a 66.4% decrease in doses reported. For children, the total number of sites administering pediatric vaccines decreased while childhood vaccination coverage decreased 4.4% overall and 5.8% in Medicaid-enrolled children. Conclusions. The critical challenge is to return to prepandemic levels of vaccine doses administered as well as to catch up individuals for vaccinations missed. (Am J Public Health. 2021;111(11):2027-2035. https://doi.org/10.2105/AJPH.2021.306474).

Decline in Child Vaccination Coverage During the COVID-19 Pandemic - Michigan Care Improvement Registry, May 2016-May 2020.

On March 13, 2020, the United States declared a national state of emergency to control the pandemic spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). Public health response measures to mitigate the pandemic have centered on social distancing and quarantine policies, including shelter-in-place and stay-at-home orders. Michigan implemented a stay-at-home order on March 23, 2020, to facilitate social distancing (2). Such strategies might result in decreased accessibility to routine immunization services, leaving children at risk for vaccine-preventable diseases and their complications (3). To evaluate whether vaccination coverage has changed during the pandemic, data from the Michigan Care Improvement Registry (the state's immunization information system) (MCIR) were analyzed. Changes in vaccine doses administered to children and the effects of those changes on up-to-date status were examined for vaccinations recommended at milestone ages corresponding to the end of an Advisory Committee on Immunization Practices (ACIP) recommendation period for one or more vaccines (4).

Population Analysis of Anidulafungin in Infants to Older Adults With Confirmed or Suspected Invasive Candidiasis.

In a pooled population analysis, we investigated the pharmacokinetics of i.v. anidulafungin in four studies across a full range of adult and pediatric ages in patients with confirmed, suspected, or at high risk of invasive candidiasis (IC). Relationships between anidulafungin exposure and key efficacy end points (global response of success and all-cause mortality) and safety end points (all-cause hepatic or gastrointestinal adverse events) in all patients and separately in pediatric patients and the appropriate dosing regimen for IC treatment in pediatric patients were evaluated. Pediatric patients received a 3.0 mg/kg (maximum 200 mg) i.v. loading dose and 1.5 mg/kg (maximum 100 mg) daily thereafter. Adults received a 200 mg i.v. loading dose and 100 mg daily thereafter. Estimated systemic anidulafungin exposures were similar across age groups (neonates to adults) at the weight-based doses studied in pediatric patients. No clear associations were identified between anidulafungin exposure and efficacy or safety end points.

Safety, Efficacy and Pharmacokinetics of Anidulafungin in Patients 1 Month to <2 Years of Age With Invasive Candidiasis, Including Candidemia.

Nineteen patients 1 month to <2 years of age with (n = 16) or at high risk of (n = 3) invasive candidiasis received anidulafungin for 5-35 days (3 mg/kg day 1, 1.5 mg/kg daily thereafter) followed by optional fluconazole (NCT00761267). Most treatment-emergent adverse events were mild/moderate, and no treatment-related deaths occurred. End of intravenous therapy global response success rate was 68.8%. Pharmacokinetics were similar to adult patients.

Collaborative Learning in Radiology: From Peer Review to Peer Learning and Peer Coaching.

BACKGROUND: A Radiology Research Alliance Task Force was assembled in 2018 to review the literature on peer review and report on best practices for peer learning and peer coaching. FINDINGS: This report provides a historical perspective on peer review and the transition to peer collaborative learning and peer coaching. Most forms of current peer review have fulfilled regulatory requirements but have failed to significantly impact quality improvement or learning opportunities. Peer learning involves joint intellectual efforts by two or more individuals to study best practices and review error collaboratively. Peer coaching is a process in which individuals in a trusted environment work to expand, refine, and build new skills in order to facilitate self-directed learning and professional growth. We discuss the value in creating opportunities for peer learning and peer coaching. CONCLUSION: Peer collaborative learning combined with peer coaching provides opportunities for teams to learn and grow together, benefit from each other's expertise and experience, improve faculty morale, and provide more opportunities for collaborations between faculty.

Effect of intra-op morphine on children with OSA undergoing tonsillectomy.

OBJECTIVES: 1. To compare outcomes after tonsillectomy for pediatric patients with obstructive sleep apnea (OSA) given morphine intra-operatively and post operatively compared to those who were not - specifically Recovery Room (RR) time, length of stay (LOS), Emergency Department (ER) visits. STUDY DESIGN: Retrospective case series with chart review. SETTING: Tertiary care children's hospital. SUBJECTS AND METHODS: All children between 1 and 17 years old who had undergone tonsillectomy in a single institution from 2013 to 2016. Comparison between children who had received morphine intra-operatively was made for outcomes. RESULTS: 556 patients were included, 73 patients had morphine intraoperatively and 483 did not; these latter children were older (8.8 vs 6.5 years, P < 0.001), and had fewer episodes of obstructive apnea and hypopnea (AHI 4.47 vs 10.15, p = 0.003) than children who did not receive intra-op morphine. There were no differences in co-morbidities including asthma, whether they had a sleep study, time in the operating room, emergence time, RR time, airway complications, IMC/PICU admission for respiratory distress, ER visits, readmissions, bleeding or post-discharge nurse phone calls. There was a longer LOS (25.9 vs 21.4 h, P = 0.011) for the group receiving intra-op morphine. CONCLUSION: Children with OSA who receive intra-op morphine have a longer LOS suggesting that its use should be examined more closely in this population.

Down regulation of p-coumarate 3-hydroxylase in petunia uniquely alters the profile of emitted floral volatiles.

Petunia × hybrida cv 'Mitchell Diploid' floral volatile benzenoid/phenylpropanoid (FVBP) biosynthesis ultimately produces floral volatiles derived sequentially from phenylalanine, cinnamic acid, and p-coumaric acid. In an attempt to better understand biochemical steps after p-coumaric acid production, we cloned and characterized three petunia transcripts with high similarity to p-coumarate 3-hydroxylase (C3H), hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyl transferase (HCT), and caffeoyl shikimate esterase (CSE). Transcript accumulation of PhC3H and PhHCT was highest in flower limb tissue during open flower stages. PhCSE transcript accumulation was also highest in flower limb tissue, but it was detected earlier at initial flower opening with a bell-shaped distribution pattern. Down regulation of endogenous PhC3H transcript resulted in altered transcript accumulation of many other FVBP network transcripts, a reduction in floral volatiles, and the emission of a novel floral volatile. Down regulation of PhHCT transcript did not have as large of an effect on floral volatiles as was observed for PhC3H down regulation, but eugenol and isoeugenol emissions were significantly reduced on the downstream floral volatiles. Together these results indicate that PhC3H is involved in FVBP biosynthesis and the reduction of PhC3H transcript influences FVBP metabolism at the network level. Additional research is required to illustrate PhHCT and PhCSE functions of petunia.

Postoperative Bleeding Associated with Ibuprofen Use after Tonsillectomy: A Meta-analysis.

OBJECTIVE: To better quantify the risk of ibuprofen-associated posttonsillectomy hemorrhage (PTH). DATA SOURCES: PUBMED/MEDLINE, Web of Science, and Cochrane Clinical Trials Database. REVIEW METHOD: Literature searches were performed for English-language publications containing the terms tonsillectomy, ibuprofen, and tonsillectomy from database inception to May 2017. Human clinical trials, prospective cohort studies, and retrospective cohort studies related to tonsillectomy, ibuprofen use, and posttonsillectomy hemorrhage among pediatric patients were selected. Electronic searches revealed 151 studies, of which 12 were deemed eligible for analysis. Studies were weighted according to level of evidence and risk of bias. RESULTS: Pooling of results across all studies showed a statistically significant increase in PTH among the patients taking ibuprofen (odds ratio, 1.38; 95% confidence interval, 1.11-1.72). The I2 statistic of 20.8% demonstrates overall low study heterogeneity and good comparability of the results. CONCLUSION: Our meta-analysis of available cohort studies and randomized controlled trials (RCTs) shows possible increased tendency to PTH with the use of ibuprofen. This has not been demonstrated in other studies and systematic reviews because their analyses were limited by use of multiple nonsteroidal anti-inflammatory drugs and inclusion of studies limited to the perioperative period and low sample size. However, the current analysis is limited due to inclusion of many retrospective cohort studies with unclear follow-up and no blinding. Further RCTs will be required to investigate this trend toward increased PTH.

Reducing Door-to-Needle Times for Ischaemic Stroke to a Median of 30 Minutes at a Community Hospital.

BACKGROUND: Alteplase is an effective treatment for ischaemic stroke patients, and it is widely available at all primary stroke centres. The effectiveness of alteplase is highly time-dependent. Large tertiary centres have reported significant improvements in their door-to-needle (DTN) times. However, these same improvements have not been reported at community hospitals. METHODS: Red Deer Regional Hospital Centre (RDRHC) is a community hospital of 370 beds that serves approximately 150,000 people in their acute stroke catchment area. The RDRHC participated in a provincial DTN improvement initiative, and implemented a streamlined algorithm for the treatment of stroke patients. During this intervention period, they implemented the following changes: early alert of an incoming acute stroke patient to the neurologist and care team, meeting the patient immediately upon arrival, parallel work processes, keeping the patient on the Emergency Medical Service stretcher to the CT scanner, and administering alteplase in the imaging area. Door-to-needle data were collected from July 2007 to December 2017. RESULTS: A total of 289 patients were treated from July 2007 to December 2017. In the pre-intervention period, 165 patients received alteplase and the median DTN time was 77 minutes [interquartile range (IQR): 60-103 minutes]; in the post-intervention period, 104 patients received alteplase and the median DTN time was 30 minutes (IQR: 22-42 minutes) (p < 0.001). The annual number of patients that received alteplase increased from 9 to 29 in the pre-intervention period to annual numbers of 41 to 63 patients in the post-intervention period. CONCLUSION: Community hospitals staffed with community neurologists can achieve median DTN times of 30 minutes or less.

CONTEXTE: L'altéplase est un traitement efficace dans le cas de patients victimes d'AVC ischémiques et demeure largement disponible dans les centres de soins de niveau primaire dédiés aux AVC. Cela dit, son efficacité dépend fortement des délais en fonction desquels on peut l'administrer. À cet égard, les centres de soins de niveau tertiaire ont fait état d'importantes améliorations en ce qui regarde leurs délais entre l'arrivée de patients et l'injection d'un traitement thrombolytique. Toutefois, il semble que de telles améliorations n'ont pas été signalées dans les hôpitaux communautaires. MÉTHODES: Le Red Deer Regional Hospital Centre (RDRHC) est un hôpital communautaire de 370 lits qui dessert approximativement 150 000 personnes dans sa zone d'attraction. Cet hôpital a participé à une initiative provinciale de réduction des délais mentionnés ci-dessus. Pour ce faire, il a mis au point un algorithme simplifié en vue du traitement de patients victimes d'AVC. Au cours de cette période d'intervention, les mesures de changement suivantes ont donc été adoptées : des alertes précoces transmises à un neurologue et aux équipes soignantes au moment de l'admission de patients victimes d'AVC aigus ; des rencontres immédiates avec les patients, et ce, dès leur arrivée à l'hôpital ; des processus de travail menés de façon parallèle ; le maintien des patients dans une civière d'ambulance jusqu'à temps qu'on puisse les conduire à un tomodensitomètre ; enfin, le fait d'administrer l'altéplase en fonction de la zone atteinte révélée par imagerie. Soulignons enfin que nos données en matière de réduction des délais ont été collectées de juillet 2007 à décembre 2017. RÉSULTATS: Au total, 289 patients ont été traités durant cette période. Au cours de la période antérieure à l'initiative évoquée précédemment, 165 patients ont bénéficié d'un traitement à l'altéplase ; les délais médians entre l'arrivée des patients et l'injection de ce médicament thrombolytique étaient alors de 77 minutes (EI : 60-103 minutes). Une fois mise en place l'initiative de réduction des délais, 104 patients ont reçu un traitement à l'altéplase ; cette fois, les délais médians du RDRHC étaient de 30 minutes (EI : 22-42 minutes ; p < 0,001). Fait à noter, le nombre annuel de patients ayant bénéficié de l'altéplase est passé de 9 à 29 durant la période pré-initiative et de 41 à 63 lors de la période post-initiative. CONCLUSION: Dans le cas des hôpitaux communautaires disposant de neurologues réguliers, il est possible de parvenir à des délais de 30 minutes ou moins entre l'arrivée de patients et l'injection d'un traitement thrombolytique.

The mental demands of leadership in complex adaptive systems.

After a decade of calls for healthcare transformation, there is a convergence of themes in our general orienting models. The core metaphor of health system as machine (with closed boundaries, linear functions, and controlled predictable outputs) has given way to health as ecosystem (with open boundaries, non-linear functions, multiple interdependencies, and no single locus of control over outcomes). Current developmental psychology theory suggests that people construct their reality, and interact with their world, based on the epistemology (or "action-logic" or "mindset") of their stage of development. Through this lens, the skills for leading large-scale change in our increasingly complex world require significant cognitive and interpersonal development. The concept of vertical development may be an underemphasized aspect of system change. This article will discuss a new set of leadership skills and frameworks that emerge in the nexus of complex adaptive systems and adult development theory.

Sleep study indices and early post-tonsillectomy outcomes.

OBJECTIVES: To investigate the relationships between preoperative sleep study findings of children undergoing adenotonsillectomy anesthesia emergence time, recovery room time, and length of stay. STUDY DESIGN: Retrospective case series with chart review. SETTING: Tertiary care children's hospital. SUBJECTS AND METHODS: All children aged 1-17 years who had undergone adenotonsillectomy between 2013 and 2016 were included. Apnea-hypopnea index (AHI), central apnea index (CAI), oxygen saturation nadir, and end-tidal carbon dioxide were compared with the in-operating room times, recovery room time, and length of stay. RESULTS: Three hundred and fourteen patients with a mean age of 6.67 (95% CI 6.25-7.09) years were included. Mean AHI was 9.14 (95% CI 7.33-10.95), mean CI was 0.88 (95% CI 0.50-1.26), mean oxygen saturation nadir was 82.9% (95% CI 81.41-84.32), mean end-tidal carbon dioxide was 50.3 (95% CI 49.39-51.15). Mean emergence time was 16 min (95% CI 15:11-17:13 min), recovery room time was 66 min (95% CI 1:00-1:11 h), and length of stay was 25.7 h (95% CI 21:43-30:00 h). When controlled for age, gender and BMI, linear regression showed that children with a higher AHI had a significantly longer operating room and operative times (p < 0.001), emergence time (p < 0.001) and length of stay (p = 0.01). CAI was related to shorter total operating room times (p = 0.03). AHI, oxygen saturation nadir, CAI and end-tidal carbon dioxide were not associated with recovery room time. CONCLUSION: Preoperative sleep study indices are associated with longer in-operating room times and length of stay, and can be useful in planning operating room and hospital flow.

Association of ibuprofen use with post-tonsillectomy bleeding in older children.

OBJECTIVE: Evaluate post-tonsillectomy outcomes in children discharged with ibuprofen versus those without. METHODS: This was a retrospective review of children who underwent tonsillectomy ±â€¯adenoidectomy from 2012 to 2016 at a tertiary care children's hospital. Main outcome measures included bleed rates, ER visits, and nurse phone calls. RESULTS: Seven hundred and seventy-three patients were included; 504 had ibuprofen at discharge (ID) and 269 did not (NID). There were significant differences in mean age, 6.7 years in the ID group years versus 8.6 for the NID group (P < 0.001). Indication for surgery was sleep apnea in 70.5% of ID patients and 44.0% of NID patients (P < 0.001). Post-tonsillectomy bleeds occurred in 8.7% in the ID group and 5.9% of the NID group (P = 0.168). Other outcome measures revealed no significant differences between the two groups. There was no significant difference in the outcome measures between patients with sleep apnea or recurrent tonsillitis. Age was important; 12.1% of children 9-18 years versus 4.8% in children 3.1-6 years (P = 0.006) had post-tonsillectomy bleeding. For children 9-18 years old, 16.7% in the ID group bled versus 7.5% in the NID group (P = 0.039). Logistical regression revealed that age contributed to post-op bleeding, and ibuprofen contributed to number of ER visits. CONCLUSION: Ibuprofen is associated with significantly elevated post-tonsillectomy bleeding in older children, further research is needed and other analgesics should be considered.

Thinking about complexity in health: A systematic review of the key systems thinking and complexity ideas in health.

RATIONALE, AIMS, AND OBJECTIVES: As the Sustainable Development Goals are rolled out worldwide, development leaders will be looking to the experiences of the past to improve implementation in the future. Systems thinking and complexity science (ST/CS) propose that health and the health system are composed of dynamic actors constantly evolving in response to each other and their context. While offering practical guidance for steering the next development agenda, there is no consensus as to how these important ideas are discussed in relation to health. This systematic review sought to identify and describe some of the key terms, concepts, and methods in recent ST/CS literature. METHOD: Using the search terms "systems thinkin * AND health OR complexity theor* AND health OR complex adaptive system* AND health," we identified 516 relevant full texts out of 3982 titles across the search period (2002-2015). RESULTS: The peak number of articles were published in 2014 (83) with journals specifically focused on medicine/healthcare (265) and particularly the Journal of Evaluation in Clinical Practice (37) representing the largest number by volume. Dynamic/dynamical systems (n = 332), emergence (n = 294), complex adaptive system(s) (n = 270), and interdependent/interconnected (n = 263) were the most common terms with systems dynamic modelling (58) and agent-based modelling (43) as the most common methods. CONCLUSIONS: The review offered several important conclusions. First, while there was no core ST/CS "canon," certain terms appeared frequently across the reviewed texts. Second, even as these ideas are gaining traction in academic and practitioner communities, most are concentrated in a few journals. Finally, articles on ST/CS remain largely theoretical illustrating the need for further study and practical application. Given the challenge posed by the next phase of development, gaining a better understanding of ST/CS ideas and their use may lead to improvements in the implementation and practice of the Sustainable Development Goals.

Effect of aperture number on pollen germination, survival and reproductive success in Arabidopsis thaliana.

Background and Aims: Pollen grains of flowering plants display a fascinating diversity of forms, including diverse patterns of apertures, the specialized areas on the pollen surface that commonly serve as the sites of pollen tube initiation and, therefore, might play a key role in reproduction. Although many aperture patterns exist in angiosperms, pollen with three apertures (triaperturate) constitutes the predominant pollen type found in eudicot species. The aim of this study was to explore whether having three apertures provides selective advantages over other aperture patterns in terms of pollen survival, germination and reproductive success, which could potentially explain the prevalence of triaperturate pollen among eudicots. Methods: The in vivo pollen germination, pollen tube growth, longevity and competitive ability to sire seeds were compared among pollen grains of Arabidopsis thaliana with different aperture numbers. For this, an arabidopsis pollen aperture series was used, which included the triaperturate wild type, as well as mutants without an aperture (inaperturate) and with more than three apertures. Key Results: Aperture number appears to influence pollen grain performance. In most germination and longevity experiments, the triaperturate and inaperturate pollen grains performed better than pollen with higher aperture numbers. In mixed pollinations, in which triaperturate and inaperturate pollen were forced to compete with each other, the triaperturate pollen outperformed the inaperturate pollen. Conclusions: Triaperturate pollen grains might provide the best trade-off among various pollen performance traits, thus explaining the prevalence of this morphological trait in the eudicot clade.

Navigating systems ideas for health practice: Towards a common learning device.

Systems thinking and reference to complexity science have gained currency in health sector practice and research. The extent to which such ideas might represent a mere passing fad or might more usefully be mobilized to tackle wicked problems in health systems is a concern underpinning this paper. Developing the usefulness of the systems idea requires appreciating how systems ideas are used essentially as constructs conceptually bounded by practitioners. Systems are used for purposes of understanding and engaging the reality of health issues, with the intent of transforming the reality into one that is more manageable, equitable, and sustainable. We examine some manifestations of the systems idea in health practice and the traditions of systems practice that variously make use of them. This provides a platform for proposing a systems thinking in (health) practice heuristic: a learning device supporting how different tools and methods can address "wicked problems" in health praxis. The device is built on the use of "conversation" as a metaphor to help practitioners use systems ideas in tandem with existing disciplinary and professional skills and methods. We consider how the application of the heuristic requires, and helps to develop, human characteristics of humility, empathy, and recognition of fallibility.

Vaccination Timeliness at Age 24 Months in Michigan Children Born 2006-2010.

INTRODUCTION: Delays in vaccination can stymie the development of herd immunity, and a large proportion of children in the U.S. are known not to receive vaccines on time. This study quantifies delays in vaccination, compares vaccination timeliness to the proportion of children vaccinated, and evaluates the impact of combination vaccine use and timely administration of hepatitis B vaccine birth dose on vaccine timeliness among Michigan children. METHODS: This retrospective cohort study used data from the Michigan Care Improvement Registry-the state immunization information system-for children born 2006-2010. Children aged 24 months as of December 31, 2012, were included. The proportion of children with timely administration of vaccine doses was calculated, and the mean days of vaccination delay with SD were reported. RESULTS: Among 620,592 Michigan children, 42.2% had received all vaccines, but only 13.2% were vaccinated on time by age 24 months. Children's vaccinations were delayed an average of 59.2 (SD=91.2) days by age 24 months for all recommended vaccine doses. Children who received a timely hepatitis B vaccine birth dose or who received a combination vaccine had less delay in vaccination. CONCLUSIONS: Michigan children have high vaccination coverage based on standard measures but few receive these vaccines on time. Promoting use of combination vaccines may improve parental compliance with timely vaccination of children.

The application of systems thinking concepts, methods, and tools to global health practices: An analysis of case studies.

OBJECTIVES: This review of systems thinking (ST) case studies seeks to compile and analyse cases from ST literature and provide practitioners with a reference for ST in health practice. Particular attention was given to (1) reviewing the frequency and use of key ST terms, methods, and tools in the context of health, and (2) extracting and analysing longitudinal themes across cases. METHODS: A systematic search of databases was conducted, and a total of 36 case studies were identified. A combination of integrative and inductive qualitative approaches to analysis was used. RESULTS: Most cases identified took place in high-income countries and applied ST retrospectively. The most commonly used ST terms were agent/stakeholder/actor (n = 29), interdependent/interconnected (n = 28), emergence (n = 26), and adaptability/adaptation (n = 26). Common ST methods and tools were largely underutilized. Social network analysis was the most commonly used method (n = 4), and innovation or change management history was the most frequently used tool (n = 11). Four overarching themes were identified; the importance of the interdependent and interconnected nature of a health system, characteristics of leaders in a complex adaptive system, the benefits of using ST, and barriers to implementing ST. CONCLUSIONS: This review revealed that while much has been written about the potential benefits of applying ST to health, it has yet to completely transition from theory to practice. There is however evidence of the practical use of an ST lens as well as specific methods and tools. With clear examples of ST applications, the global health community will be better equipped to understand and address key health challenges.