Implant retention in a rabbit model of fracture-related infection.

Aims: Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model. Methods: Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST). Results: Greater bacterial burden in the early group compared to the delayed and control groups at revision surgery indicates a retraction of the infection from one to four weeks. Infection was cleared in all animals in the early and delayed groups at euthanasia, but not in the control group. Osteotomies healed in the early group, but bone healing was significantly compromised in the delayed and control groups. Conclusion: The duration of the infection from one to four weeks does not impact the success of infection clearance in this model. Bone healing, however, is impaired as the duration of the infection increases.

Single-cell sequencing shows mosaic aneuploidy in most human embryos.

Mammalian preimplantation embryos often contain chromosomal defects that arose in the first divisions after fertilization and affect a subpopulation of cells - an event known as mosaic aneuploidy. In this issue of the JCI, Chavli et al. report single-cell genomic sequencing data for rigorous evaluation of the incidence and degree of mosaic aneuploidy in healthy human in vitro fertilization (IVF) embryos. Remarkably, mosaic aneuploidy occurred in at least 80% of human blastocyst-stage embryos, with often less than 20% of cells showing defects. These findings confirm that mosaic aneuploidy is prevalent in human embryos, indicating that the process is a widespread event that rarely has clinical consequences. There are major implications for preimplantation genetic testing of aneuploidy (PGT-A), a test commonly used to screen and select IVF embryos for transfer. The application and benefit of this technology is controversial, and the findings provide more cause for caution on its use.

Exploring the Implementation of GaAsBi Alloys as Strain-Reducing Layers in InAs/GaAs Quantum Dots.

This paper investigates the effect of GaAsBi strain reduction layers (SRLs) on InAs QDs with different Bi fluxes to achieve nanostructures with improved temperature stability. The SRLs are grown at a lower temperature (370 °C) than the usual capping temperature for InAs QDs (510 °C). The study finds that GaAs capping at low temperatures reduces QD decomposition and leads to larger pyramidal dots but also increases the threading dislocation (TD) density. When adding Bi to the capping layer, a significant reduction in TD density is observed, but unexpected structural changes also occur. Increasing the Bi flux does not increase the Bi content but rather the layer thickness. The maximum Bi content for all layers is 2.4%. A higher Bi flux causes earlier Bi incorporation, along with the formation of an additional InGaAs layer above the GaAsBi layer due to In segregation from QD erosion. Additionally, the implementation of GaAsBi SRLs results in smaller dots due to enhanced QD decomposition, which is contrary to the expected function of an SRL. No droplets were detected on the surface of any sample, but we did observe regions of horizontal nanowires within the epilayers for the Bi-rich samples, indicating nanoparticle formation.

Decreasing implant load indicates spinal fusion when measured continuously.

Reliable and timely assessment of bone union between vertebrae is considered a key challenge after spinal fusion surgery. Recently, a novel sensor concept demonstrated the ability to objectively assess posterolateral fusion based on continuous implant load monitoring. The aim of this study was to investigate systematically the concept in a mono-segmental fusion model using an updated sensor setup. Three sheep underwent bilateral facetectomy at level L2-L3 and L4-L5. The segments were stabilized using two unconnected pedicle-screw-rod constructs per level. Sensing devices were attached to the rods between each pedicle screw pair and the loads were continuously monitored over 16 weeks. After euthanasia, the spines were biomechanically tested for their range of motion and high-resolution CT scans were performed to confirm the fusion success. After an initial increase in implant load until reaching a maximum (100 %) at approximately week 4, eleven out of twelve sensors measured a constant decrease in implant load to 52 ± 9 % at euthanasia. One sensor measurement was compromised by newly forming bone growing against the sensor clamp. Bridging bone at each facet and minor remnant segmental motion (<0.7°) confirmed the fusion of all motion segments. Data obtained by continuous measurement of implant loading of spinal screw-rod constructs enables objective monitoring of spinal fusion progression. The sensor concept provides valuable real-time information, offering quantifiable data as an alternative to traditional imaging techniques. However, the design of the current sensor concept needs to be matured, tailored to, and validated for the human spine.

Comparative bone healing with induced membrane technique (IMT) versus empty defects in septic and aseptic conditions in a novel rabbit humerus model.

BACKGROUND: Long bone defects resulting from primary trauma or secondary to debridement of fracture-related infection (FRI) remain a major clinical challenge. One approach often used is the induced membrane technique (IMT). The effectiveness of the IMT in infected versus non-infected settings remains to be definitively established. In this study we present a new rabbit humerus model and compare the IMT approach between animals with prior infection and non-infected equivalents. METHODS: A 5 mm defect was created in the humerus of New Zealand White rabbits (n = 53) and fixed with a 2.5 mm stainless steel plate. In the non-infected groups, the defect was either left empty (n = 6) or treated using the IMT procedure (PMMA spacer for 3 weeks, n = 6). Additionally, both approaches were applied in animals that were inoculated with Staphylococcus aureus 4 weeks prior to defect creation (n = 5 and n = 6, respectively). At the first and second revision surgeries, infected and necrotic tissues were debrided and processed for bacteriological quantification. In the IMT groups, the PMMA spacer was removed 3 weeks post implantation and replaced with a beta-tricalcium phosphate scaffold and bone healing observed for a further 10 weeks. Infected groups also received systemic antibiotic therapy. The differences in bone healing between the groups were evaluated radiographically using a modification of the radiographic union score for tibial fractures (RUST) and by semiquantitative histopathology on Giemsa-Eosin-stained sections. RESULTS: The presence of S. aureus infection at revision surgery was required for inclusion to the second stage. At the second revision surgery all collected samples were culture negative confirming successful treatment. In the empty defect group, bone healing was increased in the previously infected animals compared with non-infected controls as revealed by radiography with significantly higher RUST values at 6 weeks (p = 0.0281) and at the end of the study (p = 0.0411) and by histopathology with increased cortical bridging (80% and 100% in cis and trans cortical bridging in infected animals compared to 17% and 67% in the non-infected animals). With the IMT approach, both infected and non-infected animals had positive healing assessments. CONCLUSION: We successfully developed an in vivo model of bone defect healing with IMT with and without infection. Bone defects can heal after an infection with even better outcomes compared to the non-infected setting, although in both cases, the IMT achieved better healing.

The effects of CenteringPregnancy on maternal and infant health outcomes: a moderation analysis.

BACKGROUND: CenteringPregnancy (CP) has been expected to produce beneficial outcomes for women and their infants. However, previous studies paid little attention to testing variations in CP's effects across women from different demographic groups. This study aimed to test how multiple demographic factors (obesity, race, ethnicity, marital status and socioeconomic status) moderate CP's effects on health outcomes. METHODS: This study employed a quasi-experimental design. De-identified hospital birth data were collected from 216 CP participants and 1159 non-CP participants. We estimated the average treatment effect of CP on outcome variables as a baseline. Then we estimated the average marginal effect of CP by adding each of the moderating variables in regression adjustment models. RESULTS: CP produced salutary effects among those who were obese or overweight and unmarried as well as women with lower socioeconomic status. These salutary effects were also strengthened as maternal age increased. However, CP was ineffective for Hispanic/Latinx women. CONCLUSIONS: CP produced more beneficial health outcomes for high-risk women such as obese, unmarried women and those with lower socioeconomic status. These are meaningful findings from a public health perspective.

A practical guide to selecting facial fillers.

BACKGROUND: Dermal fillers have created a multi-billion-dollar industry. They are the second most popular form of injectable, as they primarily address volume loss, augmentation, and provide immediate results. The most popular form includes hyaluronic acid-based fillers, however, alternatives exist. OBJECTIVE: To create clinical charts to help with filler selection, injection, and addressing common complications. METHODS: The current literature and expert opinions form our two senior authors were used to create a numerical and color-coded chart based on G-prime for filler selection, as well as an anatomical table with current recommendations and pearls. We have also included a safety table with current clinical recommendation to deal with common filler-related complications. CONCLUSION: Fillers are a safe and reliable method to achieve augmentation. Filler selection in various anatomical planes plays a significant role in achieving favorable results.

Deliberative panels as a source of public knowledge: A large-sample test of the Citizens' Initiative Review.

Evolving US media and political systems, coupled with escalating misinformation campaigns, have left the public divided over objective facts featured in policy debates. The public also has lost much of its confidence in the institutions designed to adjudicate those epistemic debates. To counter this threat, civic entrepreneurs have devised institutional reforms to revitalize democratic policymaking. One promising intervention is the Citizens' Initiative Review (CIR), which has been adopted into law in Oregon and tested in several other states, as well as Switzerland and Finland. Each CIR gathers a demographically stratified random sample of registered voters to form a deliberative panel, which hears from pro and con advocates and neutral experts while assessing the merits of a ballot measure. After four-to-five days of deliberation, each CIR writes an issue guide for voters that identifies key factual findings, along with the most important pro and con arguments. This study pools the results of survey experiments conducted on thirteen CIRs held from 2010 to 2018, resulting in a dataset that includes 67,120 knowledge scores collected from 10,872 registered voters exposed to 82 empirical claims. Analysis shows that reading the CIR guide had a positive effect on voters' policy knowledge, with stronger effects for those holding greater faith in deliberation. We found little evidence of directional motivated reasoning but some evidence that reading the CIR statement can spark an accuracy motivation. Overall, the main results show how trust in peer deliberation provides one path out of the maze of misinformation shaping voter decisions during elections.

Unhealthy herds and the predator-spreader: Understanding when predation increases disease incidence and prevalence.

Disease ecologists now recognize the limitation behind examining host-parasite interactions in isolation: community members-especially predators-dramatically affect host-parasite dynamics. Although the initial paradigm was that predation should reduce disease in prey populations ("healthy herds hypothesis"), researchers have realized that predators sometimes increase disease in their prey. These "predator-spreaders" are now recognized as critical to disease dynamics, but empirical research on the topic remains fragmented. In a narrow sense, a "predator-spreader" would be defined as a predator that mechanically spreads parasites via feeding. However, predators affect their prey and, subsequently, disease transmission in many other ways such as altering prey population structure, behavior, and physiology. We review the existing evidence for these mechanisms and provide heuristics that incorporate features of the host, predator, parasite, and environment to understand whether or not a predator is likely to be a predator-spreader. We also provide guidance for targeted study of each mechanism and quantifying the effects of predators on parasitism in a way that yields more general insights into the factors that promote predator spreading. We aim to offer a better understanding of this important and underappreciated interaction and a path toward being able to predict how changes in predation will influence parasite dynamics.

In Vitro Testing and Clinical Handling of a Novel Implant Positioning Technology for Proximal Humeral Plating.

BACKGROUND AND OBJECTIVES: Fractures of the proximal humerus are common, particularly in elderly populations. Anatomical locking plates target stabilization with a multitude of screws spanning into the humeral head. Sound implant placement and screw length determination are key for a successful clinical outcome but are difficult to obtain from planar X-rays. A novel implant positioning technology for proximal humerus plating (Xin1) outputs screw lengths suggestions and plate position based on hole projections in conventional X-ray images. This study investigated the performance of a prototype Xin1 system in a postmortem (in vitro) experiment as well as in a clinical handling test. MATERIALS AND METHODS: For in vitro testing, twelve shoulders from six anatomical specimens were randomized into two groups to compare the Xin1 technique to the conventional operation in terms of surgical precision, procedure time and X-ray exposure. For the clinical trial, 11 patients undergoing plating of the proximal humerus were included. The aim was to investigate clinical handling of the Xin1 marker clip and to retrospectively evaluate the system performance in a real-life fracture situation. Image pairs before and after insertion of the proximal screws were retrospectively processed to investigate the influence of potential bone fragment shifts on the system output. RESULTS: In the postmortem experiment, the use of the system significantly improved the surgical precision (52% error reduction), procedure time (38% shorter) and radiation exposure (64% less X-rays). Clinical handling demonstrated seamless embedding of the marker clip into existing clinical workflows without adverse events reported. Retrospective X-ray analysis on six eligible patients revealed differences in the calculated screw lengths of ≤2 mm before and after screw insertion for five patients. In one patient, the screw lengths differed up to 8 mm, which might indicate displacement of the head fragment. CONCLUSIONS: Results suggest a strong potential of the Xin1 assistance technology to enhance the surgical procedure and patient outcomes in the rising incidence of osteoporotic humeral fractures. Robust performance in a real-life fracture situation was observed. In-depth validation of the system is, however, needed before placing it into clinical practice.

Prognostic and therapeutic potential of microRNAs for fracture healing processes and non-union fractures: A systematic review.

BACKGROUND: Approximately 10% of all bone fractures result in delayed fracture healing or non-union; thus, the identification of biomarkers and prognostic factors is of great clinical interest. MicroRNAs (miRNAs) are known to be involved in the regulation of the bone healing process and may serve as functional markers for fracture healing. AIMS AND METHODS: This systematic review aimed to identify common miRNAs involved in fracture healing or non-union fractures using a qualitative approach. A systematic literature search was performed with the keywords 'miRNA and fracture healing' and 'miRNA and non-union fracture'. Any original article investigating miRNAs in fracture healing or non-union fractures was screened. Eventually, 82 studies were included in the qualitative analysis for 'miRNA and fracture healing', while 19 were selected for the 'miRNA and fracture non-union' category. RESULTS AND CONCLUSIONS: Out of 151 miRNAs, miR-21, miR-140 and miR-214 were the most investigated miRNAs in fracture healing in general. miR-31-5p, miR-221 and miR-451-5p were identified to be regulated specifically in non-union fractures. Large heterogeneity was detected between studies investigating the role of miRNAs in fracture healing or non-union in terms of patient population, sample types and models used. Nonetheless, our approach identified some miRNAs with the potential to serve as biomarkers for non-union fractures, including miR-31-5p, miR-221 and miR-451-5p. We provide a discussion of involved pathways and suggest on alignment of future research in the field.

Season and prey identity mediate the effect of predators on parasites in rodents: a test of the healthy herds hypothesis.

The healthy herds hypothesis (HHH) suggests that predators decrease parasitism in their prey. Repeated tests of this hypothesis across a range of taxa and ecosystems have revealed significant variation in the effect of predators on parasites in prey. Differences in the response to predators (1) between prey taxa, (2) between seasons, and (3) before and after catastrophic disturbance are common in natural systems, but typically ignored in empirical tests of the HHH. We used a predator exclusion experiment to measure the effect of these heterogeneities on the tri-trophic interaction among predators, parasites and prey. We experimentally excluded mammalian predators from the habitats of hispid cotton rats (Sigmodon hispidus) and cotton mice (Peromyscus gossypinus) and measured the effect of exclusion on gastrointestinal parasites in these rodents. Our experiment spanned multiple seasons and before and after a prescribed burn. We found that the exclusion of the same predators had opposite effects on the parasites of small mammal prey species. Additionally, we found that the effect of mammal exclusion on parasitism differed before versus after fire disturbance. Finally, we saw that the effect of predator exclusion was highly dependent on prey capture season. Significant effects of exclusion emerged primarily in the fall and winter months. The presence of so many different effects in one relatively simple system suggests that predator effects on parasites in prey are highly context dependent.

Epidemic time series similarity is related to geographic distance and age structure.

Objective: More similar locations may have similar infectious disease dynamics. There is clear overlap in putative causes for epidemic similarity, such as geographic distance, age structure, and population size. We compare the effects of these potential drivers on epidemic similarity compared to a baseline assumption that differences in the basic reproductive number (R 0) will translate to differences in epidemic trajectories. Methods: Using COVID-19 case counts from United States counties, we explore the importance of geographic distance, population size differences, and age structure dissimilarity on resulting epidemic similarity. Results: We find clear effects of geographic space, age structure, population size, and R 0 on epidemic similarity, but notably the effect of age structure was stronger than the baseline assumption that differences in R 0 would be most related to epidemic similarity. Conclusions: Together, this highlights the role of spatial and demographic processes on SARS-CoV2 epidemics in the United States.

Continuous Implant Load Monitoring to Assess Bone Healing Status-Evidence from Animal Testing.

Background and Objectives: Fracture healing is currently assessed through qualitative evaluation of radiographic images, which is highly subjective in nature. Radiographs can only provide snapshots in time, which are limited due to logistics and radiation exposure. We recently proposed assessing the bone healing status through continuous monitoring of the implant load, utilizing an implanted sensor system, the Fracture Monitor. The device telemetrically transmits statistically derived implant parameters via the patient's mobile phone to assist physicians in diagnostics and treatment decision-making. This preclinical study aims to systematically investigate the device safety and performance in an animal setting. Materials and Methods: Mid-shaft tibial osteotomies of different sizes (0.6-30 mm) were created in eleven Swiss mountain sheep. The bones were stabilized with either a conventional Titanium or stainless-steel locking plate equipped with a Fracture Monitor. Data were continuously collected over the device's lifetime. Conventional radiographs and clinical CT scans were taken longitudinally over the study period. The radiographs were systematically scored and CTs were evaluated for normalized bone volume in the defect. The animals were euthanized after 9 months. The sensor output was correlated with the radiologic parameters. Tissue samples from the device location were histologically examined. Results: The sensors functioned autonomously for 6.5-8.4 months until energy depletion. No macroscopic or microscopic adverse effects from device implantation were observed. The relative implant loads at 4 and 8 weeks post-operation correlated significantly with the radiographic scores and with the normalized bone volume metric. Conclusions: Continuous implant load monitoring appears as a relevant approach to support and objectify fracture healing assessments and carries a strong potential to enable patient-tailored rehabilitation in the future.

Continuous Rod Load Monitoring to Assess Spinal Fusion Status-Pilot In Vivo Data in Sheep.

Background and Objectives: Spinal fusion is an effective and widely accepted intervention. However, complications such as non-unions and hardware failures are frequently observed. Radiologic imaging and physical examination are still the gold standards in the assessment of spinal fusion, despite multiple limitations including radiation exposure and subjective image interpretation. Furthermore, current diagnostic methods only allow fusion assessment at certain time points and require the patient's presence at the hospital or medical practice. A recently introduced implantable sensor system for continuous and wireless implant load monitoring in trauma applications carries the potential to overcome these drawbacks, but transferability of the principle to the spine has not been demonstrated yet. Materials and Methods: The existing trauma sensor was modified for attachment to a standard pedicle-screw-rod system. Two lumbar segments (L2 to L4) of one Swiss white alpine sheep were asymmetrically instrumented. After facetectomy, three sensors were attached to the rods between each screw pair and activated for measurement. The sheep was euthanized 16 weeks postoperatively. After radiological assessment the spine was explanted and loaded in flexion-extension to determine the range of motion of the spinal segments. Sensor data were compared with mechanical test results and radiologic findings. Results: The sensors measured physiological rod loading autonomously over the observation period and delivered the data daily to bonded smartphones. At euthanasia the relative rod load dropped to 67% of the respective maximum value for the L23 segment and to 30% for the L34 segment. In agreement, the total range of motion of both operated segments was lower compared to an intact reference segment (L23: 0.57°; L34: 0.49°; intact L45: 4.17°). Radiologic assessment revealed fusion mass in the facet joint gaps and bilateral bridging bone around the joints at both operated segments. Conclusions: Observations of this single-case study confirm the basic ability of continuous rod load measurement to resolve the spinal fusion process as indicated by a declining rod load with progressing bone fusion. A strong clinical potential of such technology is eminent, but further data must be collected for final proof of principle.

Process, resource and success factors associated with chimeric antigen receptor T-cell therapy for multiple myeloma.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy represents a new frontier in multiple myeloma. It is important to understand critical success factors (CSFs) that may optimize its use in this therapeutic area. Methods: We estimated the CAR-T process using time-driven activity-based costing. Information was obtained through interviews at four US oncology centers and with payer representatives, and through publicly available data. Results: The CAR-T process comprises 13 steps which take 177 days; it was estimated to include 46 professionals and ten care settings. CSFs included proactive collaboration, streamlined reimbursement and CAR-T administration in alternative settings when possible. Implementing CSFs may reduce episode time and costs by 14.4 and 13.2%, respectively. Conclusion: Our research provides a blueprint for improving efficiencies in CAR-T therapy, thereby increasing its sustainability for multiple myeloma.

Patients with multiple myeloma can now be treated with chimeric antigen receptor T-cell (CAR-T) therapy. We studied how CAR-T therapy is used for multiple myeloma. We also studied things that could help make this therapy easier for doctors to use. The CAR-T process takes 13 steps and 177 days. It begins with the choice to use the therapy and ends about 100 days after it is used. The process uses 46 different healthcare professionals and ten different locations. We found several possible changes that can improve this process. Of these changes, three stand out. First, improved teamwork between members of the care team can help them prepare for and resolve possible problems. Second, reducing insurance red tape will make it easier to provide CAR-T therapy to patients. Third, allowing use of CAR-T therapy in places other than hospitals can help more patients receive this therapy. If applied, these three things may lower the time needed to treat patients by 14.4% and may reduce costs by 13.2%.

An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection.

Local antibiotic therapy is increasingly being recognised for its role in preventing and treating orthopaedic device-related infection (ODRI). A bioresorbable, injectable gentamicin-loaded hydrogel has been developed to deliver local antibiotics at the time of surgery with potential for both prevention and treatment of ODRI. In a prophylaxis model, the antibiotic hydrogel was compared with systemic perioperative antibiotic prophylaxis alone in twelve sheep (six per group) at the time of intramedullary (IM) nail insertion to the tibia, which was inoculated with methicillin-sensitive Staphylococcus aureus (MSSA). In a treatment model of single-stage revision surgery, adjunctive antibiotic-loaded hydrogel was compared with systemic antibiotics alone in a single stage revision of MSSA infection associated with a tibia intramedullary nail in eleven sheep (five/six per group). The primary endpoint was quantitative microbiological results of soft tissue, bone and sonicate fluid from explanted hardware at the time of euthanasia. At euthanasia, the control sheep that received no local antibiotics in the prophylaxis model were all culture-positive (median 1x108, range 7x106-3x108 colony forming units, CFU) while only two of six sheep receiving local gentamicin had any culture positive biopsies (median 1x101, range 0 - 1x105 CFU). For the treatment model, sheep receiving only systemic antibiotics were all culture-positive (median 8x105, range 2x103- 9x106 CFU) while only two of six sheep treated with gentamicin-loaded hydrogel had any culture positive biopsies (median 3x102, range 0 - 7x104 CFU). Local gentamicin concentrations measured in extracellular fluid in the tibial canal show a burst release of gentamicin from the hydrogel. Serum gentamicin concentrations peaked in both models at one day post application and were below detection limit thereafter. This study has demonstrated the effective use of a locally delivered antibiotic hydrogel for both the prevention and treatment of ODRI that is superior to that of systemic antibiotics alone. Future studies will endeavour to translate from preclinical to clinical research trials.

Infectious disease: Dog diets may drive transmission cycles in human Guinea worm disease.

Domestic dogs have an important role in the ecology of transmission of the Guinea worm, a debilitating human parasite. A new study documents how fish content in dogs' diets can predict Guinea worm infection status, suggesting additional avenues for control.

Investigating Flubendazole as an Anthelmintic Treatment for Guinea Worm (Dracunculus medinensis): Clinical Trials in Laboratory-Reared Ferrets and Domestic Dogs in Chad.

Dracunculus medinensis (Guinea worm [GW]), a zoonotic nematode targeted for eradication, has been managed using interventions aimed at humans; however, increases in domestic dog GW infections highlight the need for novel approaches. We conducted two clinical trials evaluating the efficacy of subcutaneously injected flubendazole (FBZ) as a treatment of GW infection. The first trial was conducted administering FBZ to experimentally infected ferrets; the second trial involved administering FBZ or a placebo to domestic dogs in the Republic of Tchad (Chad). We found contrasting results between the two trials. When adult gravid female GW were recovered from ferrets treated with FBZ, larvae presented in poor condition, with low to no motility, and an inability to infect copepods. Histopathology results indicated a disruption to morulae development within uteri of worms from treated animals. Results from the trial in Chadian dogs failed to indicate significant treatment of or prevention against GW infection. However, the difference in treatment intervals (1 month for ferrets and 6 months for dogs) or the timing of treatment (ferrets were treated later in the GW life-cycle than dogs) could explain different responses to the subcutaneous FBZ injections. Both trials provided valuable data guiding the use of FBZ in future trials (such as decreasing treatment intervals or increasing the dose of FBZ in dogs to increase exposure), and highlighted important lessons learned during the implementation of a field-based, double-blinded randomized control trial in Chadian dogs.