Counting the Capital's cats: Estimating drivers of abundance of free-roaming cats with a novel hierarchical model.

Free-roaming cats are a conservation concern in many areas but identifying their impacts and developing mitigation strategies requires a robust understanding of their distribution and density patterns. Urban and residential areas may be especially relevant in this process because free-roaming cats are abundant in these anthropogenic landscapes. Here, we estimate the occupancy and density of free-roaming cats in Washington D.C. and relate these metrics to known landscape and social factors. We conducted an extended camera trap survey of public and private spaces across D.C. and analyzed data collected from 1483 camera deployments from 2018 to 2020. We estimated citywide cat distribution by fitting hierarchical occupancy models and further estimated cat abundance using a novel random thinning spatial capture-recapture model that allows for the use of photos that can and cannot be identified to individual. Within this model, we utilized individual covariates that provided identity exclusions between photos of unidentifiable cats with inconsistent coat patterns, thus increasing the precision of abundance estimates. This combined model also allowed for unbiased estimation of density when animals cannot be identified to individual at the same rate as for free-roaming cats whose identifiability depended on their coat characteristics. Cat occupancy and abundance declined with increasing distance from residential areas, an effect that was more pronounced in wealthier neighborhoods. There was noteworthy absence of cats detected in larger public spaces and forests. Realized densities ranged from 0.02 to 1.75 cats/ha in sampled areas, resulting in a district-wide estimate of ~7296 free-roaming cats. Ninety percent of cat detections lacked collars and nearly 35% of known individuals were ear-tipped, indicative of district Trap-Neuter-Return (TNR) programs. These results suggest that we mainly sampled and estimated the unowned cat subpopulation, such that indoor/outdoor housecats were not well represented. The precise estimation of cat population densities is difficult due to the varied behavior of subpopulations within free-roaming cat populations (housecats, stray and feral cats), but our methods provide a first step in establishing citywide baselines to inform data-driven management plans for free-roaming cats in urban environments.

Owned dog population size and ownership patterns in Costa Rica.

Dogs (Canis lupus familiaris) are one of the most common pets around the world but ownership patterns and human-dog interactions have been changing, particularly in developing nations. We conducted household surveys in Costa Rica to characterize dog ownership, the owned dog population, where dogs were confined at night and in the morning, and behaviors regarding selected dog care issues. We also compared these results to similar questionnaires used in Costa Rica over the past 20 years. We found 76% of households in Costa Rica owned at least one dog and on average there were about 1.4 dogs owned per household. These dog ownership rates are higher than previous estimates. The probability of owning a dog was highest on farms and lowest in single family dwellings without a yard, higher among respondents that owned their homes and decreasing with increasing human population density The total number of owned dogs in Costa Rica was estimated to be 2,222,032 (95% confidence intervals: 1,981,497-2,503,751). The sterilization rate for homed dogs in 2020 was approximately 62% (females: 67%, males: 61%) which is higher than the 18% of owned dogs that were sterilized in a 2003 survey. Overall, only 1.2% (95% CI: 0.3-2.5%) of owned dogs slept on the street with a slightly higher proportion on the street at 8 am. The number of owned dogs roaming the streets at night nation-wide was estimated to be 27,208 (95% CI: 7,557-56,619) compared to 43,142 (95% CI: 20,118-73,618) on the street at 8 am. The number of unowned free-roaming dogs in Costa Rica has never been estimated but we can generate some idea of the size of the unowned dog population by determining the proportion of free-roaming dogs on the street wearing collars. There was a negative relationship between human population density and owned dogs being on the street meaning fewer dogs roam the streets in highly populated areas compared to less populated areas. Overall, we identify trends against which future progress can be measured and provide information that are critical in designing effective humane dog management programs in Costa Rica in the future.

Direct and Indirect Factors Influencing Cat Outcomes at an Animal Shelter.

Animal shelters play a vital role for pets, such as transitioning animals between homes, from outdoor communities into homes, caring for unadoptable and community animals, and providing a breadth of veterinary and welfare services. The goal of shelters is to move cats to their appropriate outcome as quickly as possible, which for many animals, is to rehome them as quickly as possible through adoption. Therefore, the ability to identify pre-existing factors, particularly those occurring outside the walls of the shelter, which result in specific outcomes is vital. In this study, we used structural equation modeling to test four hypotheses addressing how to predict cat outcome from a shelter in Washington, D.C. We developed four hypotheses that described how cat outcomes could be predicted, based on four general factors: (1) The characteristics of the cats; (2) The location of origin; (3) The type and date of intake; (4) The length of stay. Using 4 years of data from the Humane Rescue Alliance in Washington, D.C., we found support for each of our hypotheses. Additionally, we tested and found support for a global model, which comprised an amalgamation of our all our predictors. From the global model, we can conclude that many factors are at play in predicting cat outcomes in this shelter and very likely in many others as well. Critically, these factors are interconnected, indicating, for example, that cat characteristics mediate the influence of intake location on outcome type. Furthermore, our study highlights the importance of incorporating influences beyond the shelter when attempting to understand cat outcomes. Therefore, to modify cat outcomes most efficiently, such as increasing adoption probabilities, our results show that efforts may be most effective when incorporating multiple factors.

Experimental field evidence shows milkweed contaminated with a common neonicotinoid decreases larval survival of monarch butterflies.

Neonicotinoid insecticides are the most widely used class of insecticides in the world and can have both lethal and sub-lethal effects on non-target organisms in agricultural areas. Monarch butterflies Danaus plexippus have experienced dramatic declines in recent decades and, given that a large proportion of milkweed on the landscape grows in agricultural areas, there is concern about the negative effects of neonicotinoids on this non-target insect. In the field, we exposed common milkweed Asclepias syriaca, an obligate host plant of monarch butterflies, to agriculturally realistic levels of clothianidin, a widely used neonicotinoid insecticide. We tested whether this treatment influenced the number of eggs laid and larval survival over 2 years. Milkweeds were transplanted into 60 experimental plots alongside a corn crop planted with a clothianidin seed coat and 60 control plots alongside an untreated corn crop. The number of eggs, larvae at each stage (first to fifth instar), and the presence of other arthropods were recorded weekly from June to the end of August and survival from egg to fifth instar was estimated using a Bayesian state-space statistical model. We counted more eggs in treated plots compared to control plots, suggesting a preference for treated milkweed. The number of plots with arthropods did not differ between treatments, but within treated plots, there was a greater decrease in the number of arthropods throughout the season. There was no evidence that monarchs selected plots with fewer arthropods for oviposition. Larval survival was lower in clothianidin-treated plots compared to control plots. Our results suggest milkweed near clothianidin-treated crops can reduce larval survival of monarch butterflies. While we provide some evidence that clothianidin could also act as an ecological trap for this species, further work is needed to identify additional components of fitness, including individual egg-laying rates and survival beyond the pupal stage. Our findings add to a growing body of evidence that neonicotinoids can negatively affect non-target organisms. ​.

Correction: Multistate matrix population model to assess the contributions and impacts on population abundance of domestic cats in urban areas including owned cats, unowned cats, and cats in shelters.

[This corrects the article DOI: 10.1371/journal.pone.0192139.].

Radio-tracking reveals how wind and temperature influence the pace of daytime insect migration.

Insects represent the most diverse and functionally important group of flying migratory animals around the globe, yet their small size makes tracking even large migratory species challenging. We attached miniaturized radio transmitters (less than 300 mg) to monarch butterflies ( Danaus plexippus) and common green darner dragonflies ( Anax junius) and tracked their autumn migratory movements through southern Ontario, Canada and into the United States using an automated array of over 100 telemetry towers. The farthest estimated distance a monarch travelled in a single day was 143 km at a wind-assisted groundspeed of 31 km h-1 (8.7 m s-1) and the farthest estimated distance a green darner travelled in a single day was 122 km with a wind-assisted groundspeed of up to 77 km h-1 (21.5 m s-1). For both species, increased temperature and wind assistance positively influenced the pace of migration, but there was no effect of precipitation. While limitations to tracking such small animals remain, our approach and results represent a fundamental advance in understanding the natural history of insect migration and environmental factors that govern their movements.

National contributions to global ecosystem values.

Current conservation templates prioritize biogeographic regions with high intensity ecosystem values, such as exceptional species richness or threat. Intensity-based targets are an important consideration in global efforts, but they do not capture all available opportunities to conserve ecosystem values, including those that accrue in low intensity over large areas. We assess six globally-significant ecosystem values-intact wilderness, freshwater availability, productive marine environments, breeding habitat for migratory wildlife, soil carbon storage, and latitudinal potential for range shift in the face of climate change-to highlight opportunities for high-impact broadly-distributed contributions to global conservation. Nations can serve as a cohesive block of policy that can profoundly influence conservation outcomes. Contributions to global ecosystem values that exceed what is predicted by a nation's area alone, can give rise to countries with the capacity to act as 'conservation superpowers', such as Canada and Russia. For these conservation superpowers, a relatively small number of national policies can have environmental repercussions for the rest of the world.

Migratory monarchs that encounter resident monarchs show life-history differences and higher rates of parasite infection.

Environmental change induces some wildlife populations to shift from migratory to resident behaviours. Newly formed resident populations could influence the health and behaviour of remaining migrants. We investigated migrant-resident interactions among monarch butterflies and consequences for life history and parasitism. Eastern North American monarchs migrate annually to Mexico, but some now breed year-round on exotic milkweed in the southern US and experience high infection prevalence of protozoan parasites. Using stable isotopes (δ2 H, δ13 C) and cardenolide profiles to estimate natal origins, we show that migrant and resident monarchs overlap during fall and spring migration. Migrants at sites with residents were 13 times more likely to have infections and three times more likely to be reproductive (outside normal breeding season) compared to other migrants. Exotic milkweed might either attract migrants that are already infected or reproductive, or alternatively, induce these states. Increased migrant-resident interactions could affect monarch parasitism, migratory success and long-term conservation.

Modeling the effect of surgical sterilization on owned dog population size in Villa de Tezontepec, Hidalgo, Mexico, using an individual-based computer simulation model.

Surgical sterilization programs for dogs have been proposed as interventions to control dog population size. Models can be used to help identify the long-term impact of reproduction control interventions for dogs. The objective of this study was to determine the projected impact of surgical sterilization interventions on the owned dog population size in Villa de Tezontepec, Hidalgo, Mexico. A stochastic, individual-based simulation model was constructed and parameterized using a combination of empirical data collected on the demographics of owned dogs in Villa de Tezontepec and data available from the peer-reviewed literature. Model outcomes were assessed using a 20-year time horizon. The model was used to examine: the effect of surgical sterilization strategies focused on: 1) dogs of any age and sex, 2) female dogs of any age, 3) young dogs (i.e., not yet reached sexual maturity) of any sex, and 4) young, female dogs. Model outcomes suggested that as surgical capacity increases from 21 to 84 surgeries/month, (8.6% to 34.5% annual sterilization) for dogs of any age, the mean dog population size after 20 years was reduced between 14% and 79% compared to the base case scenario (i.e. in the absence of intervention). Surgical sterilization interventions focused only on young dogs of any sex yielded greater reductions (81% - 90%) in the mean population size, depending on the level of surgical capacity. More focused sterilization targeted at female dogs of any age, resulted in reductions that were similar to focusing on mixed sex sterilization of only young dogs (82% - 92%). The greatest mean reduction in population size (90% - 91%) was associated with sterilization of only young, female dogs. Our model suggests that targeting sterilization to young females could enhance the efficacy of existing surgical dog population control interventions in this location, without investing extra resources.

Drivers of demographic decline across the annual cycle of a threatened migratory bird.

Migratory species are rapidly declining but we rarely know which periods of the annual cycle are limiting for most species. This knowledge is needed to effectively allocate conservation resources to the periods of the annual cycle that best promote species recovery. We examined demographic trends and response to human footprint for Canada warblers (Cardellina canadensis), a threatened Neotropical migrant, using range-wide data (1993-2016) from the Monitoring Avian Productivity and Survivorship (MAPS) program on the breeding grounds. Declines in abundance were steepest in the eastern breeding region, followed by the western region. Breeding productivity did not decline in any region. In contrast, we observed declining recruitment in all regions, low apparent survival in the east and west, and a decline in apparent survival in the east. Abundance declined with increasing disturbance around MAPS stations. Between 1993 and 2009, the human footprint index on the breeding range increased by 0.11% in contrast to a 14% increase on the wintering range. Landscape-scale disturbance on the breeding grounds may influence abundance in some regions; however, the observed trends in demography and footprint suggests limitation during the non-breeding period as the likely driver of overall declines, particularly for eastern populations.

Multistate matrix population model to assess the contributions and impacts on population abundance of domestic cats in urban areas including owned cats, unowned cats, and cats in shelters.

Concerns over cat homelessness, over-taxed animal shelters, public health risks, and environmental impacts has raised attention on urban-cat populations. To truly understand cat population dynamics, the collective population of owned cats, unowned cats, and cats in the shelter system must be considered simultaneously because each subpopulation contributes differently to the overall population of cats in a community (e.g., differences in neuter rates, differences in impacts on wildlife) and cats move among categories through human interventions (e.g., adoption, abandonment). To assess this complex socio-ecological system, we developed a multistate matrix model of cats in urban areas that include owned cats, unowned cats (free-roaming and feral), and cats that move through the shelter system. Our model requires three inputs-location, number of human dwellings, and urban area-to provide testable predictions of cat abundance for any city in North America. Model-predicted population size of unowned cats in seven Canadian cities were not significantly different than published estimates (p = 0.23). Model-predicted proportions of sterile feral cats did not match observed sterile cat proportions for six USA cities (p = 0.001). Using a case study from Guelph, Ontario, Canada, we compared model-predicted to empirical estimates of cat abundance in each subpopulation and used perturbation analysis to calculate relative sensitivity of vital rates to cat abundance to demonstrate how management or mismanagement in one portion of the population could have repercussions across all portions of the network. Our study provides a general framework to consider cat population abundance in urban areas and, with refinement that includes city-specific parameter estimates and modeling, could provide a better understanding of population dynamics of cats in our communities.

Effect of Capacity for Care on cat admission trends at the Guelph Humane Society, 2011-2015.

In recent years, there has been a growing concern regarding populations of cats who are homeless. Shelters are constantly overwhelmed by the influx of cats without caregivers and are seeking solutions to enhance positive outcomes for them. In 2014, the Guelph Humane Society implemented a population management program to expedite the movement of cats through the shelter by decreasing the average nonhuman animal's length of stay using scheduled intakes to control for overcrowding and by implementing strategies to increase adoption rates. This study investigated the time trends in admission rates of cats to the Guelph Humane Society to assess the effectiveness of a population management program called Capacity for Care using a generalized linear autoregressive moving average model. From January 2011 to December 2015, a total of 3295 live cats were admitted to the Guelph Humane Society. When the analysis was adjusted to account for admissions of kittens, there was a significant reduction in admissions for adult cats (p < .01) following the introduction of the population management program. The results also showed a strong seasonal peak in total admissions during the summer months.

A general modeling framework for describing spatially structured population dynamics.

Variation in movement across time and space fundamentally shapes the abundance and distribution of populations. Although a variety of approaches model structured population dynamics, they are limited to specific types of spatially structured populations and lack a unifying framework. Here, we propose a unified network-based framework sufficiently novel in its flexibility to capture a wide variety of spatiotemporal processes including metapopulations and a range of migratory patterns. It can accommodate different kinds of age structures, forms of population growth, dispersal, nomadism and migration, and alternative life-history strategies. Our objective was to link three general elements common to all spatially structured populations (space, time and movement) under a single mathematical framework. To do this, we adopt a network modeling approach. The spatial structure of a population is represented by a weighted and directed network. Each node and each edge has a set of attributes which vary through time. The dynamics of our network-based population is modeled with discrete time steps. Using both theoretical and real-world examples, we show how common elements recur across species with disparate movement strategies and how they can be combined under a unified mathematical framework. We illustrate how metapopulations, various migratory patterns, and nomadism can be represented with this modeling approach. We also apply our network-based framework to four organisms spanning a wide range of life histories, movement patterns, and carrying capacities. General computer code to implement our framework is provided, which can be applied to almost any spatially structured population. This framework contributes to our theoretical understanding of population dynamics and has practical management applications, including understanding the impact of perturbations on population size, distribution, and movement patterns. By working within a common framework, there is less chance that comparative analyses are colored by model details rather than general principles.

Quantitative tools for implementing the new definition of significant portion of the range in the U.S. Endangered Species Act.

In 2014, the Fish and Wildlife Service (FWS) and National Marine Fisheries Service announced a new policy interpretation for the U.S. Endangered Species Act (ESA). According to the act, a species must be listed as threatened or endangered if it is determined to be threatened or endangered in a significant portion of its range (SPR). The 2014 policy seeks to provide consistency by establishing that a portion of the range should be considered significant if the associated individuals' "removal would cause the entire species to become endangered or threatened." We reviewed 20 quantitative techniques used to assess whether a portion of a species' range is significant according to the new guidance. Our assessments are based on the 3R criteria-redundancy (i.e., buffering from catastrophe), resiliency (i.e., ability to withstand stochasticity), and representation (i.e., ability to evolve)-that the FWS uses to determine if a species merits listing. We identified data needs for each quantitative technique and considered which methods could be implemented given the data limitations typical of rare species. We also identified proxies for the 3Rs that may be used with limited data. To assess potential data availability, we evaluated 7 example species by accessing data in their species status assessments, which document all the information used during a listing decision. In all species, an SPR could be evaluated with at least one metric for each of the 3Rs robustly or with substantial assumptions. Resiliency assessments appeared most constrained by limited data, and many species lacked information on connectivity between subpopulations, genetic variation, and spatial variability in vital rates. These data gaps will likely make SPR assessments for species with complex life histories or that cross national boundaries difficult. Although we reviewed techniques for the ESA, other countries require identification of significant areas and could benefit from this research.

Migration distance as a selective episode for wing morphology in a migratory insect.

BACKGROUND: Selective pressures that occur during long-distance migration can influence morphological traits across a range of taxa. In flying insects, selection should favour individuals that have wing morphologies that increase energy efficiency and survival. In monarch butterflies, differences in wing morphology between migratory and resident populations suggest that migratory populations have undergone selection for larger (as measured by length and area) and more elongated (as measured by roundness and aspect ratio) forewings. However, selection on wing morphology may also occur within migratory populations, particularly if individuals or populations consistently migrate different distances. RESULTS: Using 613 monarch butterflies that were collected on the Mexican wintering grounds between 1976 - 2014, we tested whether monarch wing traits were associated with migratory distance from their natal areas in eastern North America (migration range: 774-4430 km), as inferred by stable-hydrogen (δ2H) and -carbon (δ13C) isotopic measurements. Monarchs that migrated farther distances to reach their overwintering sites tended to have longer and larger wings, suggesting positive selective pressure during migration on wing length and area. There was no relationship between migration distances and either roundness or aspect ratio. CONCLUSIONS: Our results provide correlative evidence that the migratory period may act as a selective episode on monarch butterfly wing morphology, although selection during other portions of the annual cycle, as well as extensive mixing of individuals from various natal locations on the breeding grounds, likely counteracts directional selection of migration on morphology.

Regional climate on the breeding grounds predicts variation in the natal origin of monarch butterflies overwintering in Mexico over 38 years.

Addressing population declines of migratory insects requires linking populations across different portions of the annual cycle and understanding the effects of variation in weather and climate on productivity, recruitment, and patterns of long-distance movement. We used stable H and C isotopes and geospatial modeling to estimate the natal origin of monarch butterflies (Danaus plexippus) in eastern North America using over 1000 monarchs collected over almost four decades at Mexican overwintering colonies. Multinomial regression was used to ascertain which climate-related factors best-predicted temporal variation in natal origin across six breeding regions. The region producing the largest proportion of overwintering monarchs was the US Midwest (mean annual proportion = 0.38; 95% CI: 0.36-0.41) followed by the north-central (0.17; 0.14-0.18), northeast (0.15; 0.11-0.16), northwest (0.12; 0.12-0.16), southwest (0.11; 0.08-0.12), and southeast (0.08; 0.07-0.11) regions. There was no evidence of directional shifts in the relative contributions of different natal regions over time, which suggests these regions are comprising the same relative proportion of the overwintering population in recent years as in the mid-1970s. Instead, interannual variation in the proportion of monarchs from each region covaried with climate, as measured by the Southern Oscillation Index and regional-specific daily maximum temperature and precipitation, which together likely dictate larval development rates and food plant condition. Our results provide the first robust long-term analysis of predictors of the natal origins of monarchs overwintering in Mexico. Conservation efforts on the breeding grounds focused on the Midwest region will likely have the greatest benefit to eastern North American migratory monarchs, but the population will likely remain sensitive to regional and stochastic weather patterns.

Polymorphisms in drug-metabolizing enzymes and steady-state exemestane concentration in postmenopausal patients with breast cancer.

Discovery of clinical and genetic predictors of exemestane pharmacokinetics was attempted in 246 postmenopausal patients with breast cancer enrolled on a prospective clinical study. A sample was collected 2 h after exemestane dosing at a 1- or 3-month study visit to measure drug concentration. The primary hypothesis was that patients carrying the low-activity CYP3A4*22 (rs35599367) single-nucleotide polymorphism (SNP) would have greater exemestane concentration. Additional SNPs in genes relevant to exemestane metabolism (CYP1A1/2, CYP1B1, CYP3A4, CYP4A11, AKR1C3/4, AKR7A2) were screened in secondary analyses and adjusted for clinical covariates. CYP3A4*22 was associated with a 54% greater exemestane concentration (P<0.01). Concentration was greater in patients who reported White race, had elevated aminotransferases, renal insufficiency, lower body mass index and had not received chemotherapy (all P<0.05), and CYP3A4*22 maintained significance after adjustment for covariates (P<0.01). These genetic and clinical predictors of exemestane concentration may be useful for treatment individualization in patients with breast cancer.

Owned dog ecology and demography in Villa de Tezontepec, Hidalgo, Mexico.

Dog overpopulation in developing countries has negative implications for the health and safety of people, including the transmission of zoonotic diseases, physical attacks and intimidation to humans and animals, as well as impacts on canine welfare. Understanding the ecology and demographic characteristics of a dog population can help in the planning and monitoring of canine population control programs. Little data exist regarding demography and dynamics of domestic dog populations in semi-urban areas in Mexico. A cross-sectional study was carried out between October 21 and November 7, 2015, to characterize the dog ecology and demography in Villa de Tezontepec, Hidalgo, Mexico. A face-to-face survey was used to collect data from randomly selected households in four contiguous communities using stratified two-stage cluster sampling. Within each household, adults answered questions related to their dogs and their experiences with dog bites and aggression. A total of 328 households were interviewed, representing a participation rate of 90.9% (328/361) and 1,450 people. Approximately 65.2% of the households owned one or more dogs, with a mean of 1.3 (SD=1.5) and 2.0 (SD=1.5) owned dogs in all participant households and dog-owning households, respectively. The human: owned dog ratio for all participant households was 3.4:1 (1450/428), and for the dog-owning households was 2.3:1 (984/428). The owned dog male: female ratio was 1.4:1 (249/179). Approximately 74.4% (95.0% CI=69.8% - 78.7%) of the owned dogs were older than one year (mean age: 2.9 years; SD=2.5). The mean age of owned female dogs at first litter was 1.9 years (SD=1.2) and the mean litter size was 4.2 puppies (SD=2.1). Approximately 36.9% (95.0% CI=31.8% - 46.4%) of the females were spayed, and 14.1% (95.0% CI=10.7% - 19.7%) of the males were neutered. Only 44.9% (95.0% CI=40.1% - 49.7%) were always confined when unsupervised. Approximately 84.4% (95.0% CI=80.6% - 87.7%) were reported to have been vaccinated against rabies in 2015. The knowledge of owned dog demography and ecology provided by this study can inform local government planning of dog population control interventions, and could serve as a baseline for the development of agent-based models to evaluate the effects of different dog population control strategies on dog demography.

Implementation of a pharmacogenomics consult service to support the INGENIOUS trial.

Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding.

Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics.

Drug-drug interactions causing severe hypoglycemia due to antidiabetic drugs is a major clinical and public health problem. We assessed whether sulfonylurea use with a statin or fibrate was associated with severe hypoglycemia. We conducted cohort studies of users of glyburide, glipizide, and glimepiride plus a statin or fibrate within a Medicaid population. The outcome was a validated, diagnosis-based algorithm for severe hypoglycemia. Among 592,872 persons newly exposed to a sulfonylurea+antihyperlipidemic, the incidence of severe hypoglycemia was 5.8/100 person-years. Adjusted hazard ratios (HRs) for sulfonylurea+statins were consistent with no association. Most overall HRs for sulfonylurea+fibrate were elevated, with sulfonylurea-specific adjusted HRs as large as 1.50 (95% confidence interval (CI): 1.24-1.81) for glyburide+gemfibrozil, 1.37 (95% CI: 1.11-1.69) for glipizide+gemfibrozil, and 1.63 (95% CI: 1.29-2.06) for glimepiride+fenofibrate. Concomitant therapy with a sulfonylurea and fibrate is associated with an often delayed increased rate of severe hypoglycemia.