Survival of HIV-positive individuals with hepatitis B and C infection in Michigan.

We sought to estimate mortality and associated factors in HIV-hepatitis co-infected individuals in Michigan using a retrospective cohort study. For the study period of 1 January 2006 to 31 December 2009, all HIV-infected individuals were matched to hepatitis B and C cases. In the final Cox proportional hazards regression model, individuals of other [hazard ratio (HR) 2·2, 95% confidence interval (CI) 1·4-3·2] and black (HR 1·3, 95% CI 1·1-1·6) race had decreased survival compared to white race. Similarly, injecting drug users (IDUs) (HR 2·1, 95% CI 1·6-2·6), men who have sex with men (MSM)/IDUs (HR 1·5, 95% CI 1·1-2·2), individuals with undetermined risk (HR 1·5, 95% CI 1·2-1·9) and heterosexual practices (HR 1·4, 95% CI 1·1-1·8) had decreased survival compared to MSM. Additionally, an interaction was found between current HIV status and co-infection. Mortality in HIV-hepatitis co-infected individuals remains a continuing problem. Our study can help in planning interventions to reduce mortality in HIV-infected individuals.

Hepatitis B and C co-infection in HIV/AIDS population in the state of Michigan.

A retrospective cohort study was conducted from 1 January 2006 to 31 December 2009 in Michigan to estimate the prevalence of HIV and hepatitis co-infection and identify associated factors. The prevalence of co-infection was 4.1% [95% confidence interval (CI) 3.8-4.5]. Multivariable logistic regression analysis revealed a significant association between co-infection and being male and: of Black race [odds ratio (OR) 2.0, 95% CI 1.2-3.6] and of Other race (OR 3.5, 95% CI 1.7-7.0) compared to Hispanic race. A significant association was found between co-infection and risk categories of blood products (OR 11.1, 95% CI 6.2-20.2), injecting drug user (IDU) (OR 3.6, 95% CI 2.7-4.8) and men who have sex with men/IDU (OR 3.4, 95% CI 2.4-4.9) in addition to two interactions; one between sex and current HIV status and the other between current HIV status and age at HIV diagnosis. Our results document the changing epidemiology of HIV-hepatitis co-infection which can guide preventive measures and interventions to reduce the prevalence of hepatitis co-infection.

Palladin isoforms 3 and 4 regulate cancer-associated fibroblast pro-tumor functions in pancreatic ductal adenocarcinoma.

Pancreatic Ductal Adenocarcinoma (PDAC) has a five-year survival under 10%. Treatment is compromised due to a fibrotic-like stromal remodeling process, known as desmoplasia, which limits therapeutic perfusion, supports tumor progression, and establishes an immunosuppressive microenvironment. These processes are driven by cancer-associated fibroblasts (CAFs), functionally activated through transforming growth factor beta1 (TGFß1). CAFs produce a topographically aligned extracellular matrix (ECM) that correlates with reduced overall survival. Paradoxically, ablation of CAF populations results in a more aggressive disease, suggesting CAFs can also restrain PDAC progression. Thus, unraveling the mechanism(s) underlying CAF functions could lead to therapies that reinstate the tumor-suppressive features of the pancreatic stroma. CAF activation involves the f-actin organizing protein palladin. CAFs express two palladin isoforms (iso3 and iso4) which are up-regulated in response to TGFß1. However, the roles of iso3 and iso4 in CAF functions remain elusive. Using a CAF-derived ECM model, we uncovered that iso3/iso4 are required to sustain TGFß1-dependent CAF activation, secrete immunosuppressive cytokines, and produce a pro-tumoral ECM. Findings demonstrate a novel role for CAF palladin and suggest that iso3/iso4 regulate both redundant and specific tumor-supportive desmoplastic functions. This study highlights the therapeutic potential of targeting CAFs to restore fibroblastic anti-tumor activity in the pancreatic microenvironment.

Towards correlative imaging of plant cortical microtubule arrays: combining ultrastructure with real-time microtubule dynamics.

There are a variety of microscope technologies available to image plant cortical microtubule arrays. These can be applied specifically to investigate direct questions relating to array function, ultrastructure or dynamics. Immunocytochemistry combined with confocal laser scanning microscopy provides low resolution "snapshots" of cortical microtubule arrays at the time of fixation whereas live cell imaging of fluorescent fusion proteins highlights the dynamic characteristics of the arrays. High-resolution scanning electron microscopy provides surface detail about the individual microtubules that form cortical microtubule arrays and can also resolve cellulose microfibrils that form the innermost layer of the cell wall. Transmission electron microscopy of the arrays in cross section can be used to examine links between microtubules and the plasma membrane and, combined with electron tomography, has the potential to provide a complete picture of how individual microtubules are spatially organized within the cortical cytoplasm. Combining these high-resolution imaging techniques with the expression of fluorescent cytoskeletal fusion proteins in live cells using correlative microscopy procedures will usher in an radical change in our understanding of the molecular dynamics that underpin the organization and function of the cytoskeleton.

Dynamic Response and Residual Helmet Liner Crush Using Cadaver Heads and Standard Headforms.

Biomechanical headforms are used for helmet certification testing and reconstructing helmeted head impacts; however, their biofidelity and direct applicability to human head and helmet responses remain unclear. Dynamic responses of cadaver heads and three headforms and residual foam liner deformations were compared during motorcycle helmet impacts. Instrumented, helmeted heads/headforms were dropped onto the forehead region against an instrumented flat anvil at 75, 150, and 195 J. Helmets were CT scanned to quantify maximum liner crush depth and crush volume. General linear models were used to quantify the effect of head type and impact energy on linear acceleration, head injury criterion (HIC), force, maximum liner crush depth, and liner crush volume and regression models were used to quantify the relationship between acceleration and both maximum crush depth and crush volume. The cadaver heads generated larger peak accelerations than all three headforms, larger HICs than the International Organization for Standardization (ISO), larger forces than the Hybrid III and ISO, larger maximum crush depth than the ISO, and larger crush volumes than the DOT. These significant differences between the cadaver heads and headforms need to be accounted for when attempting to estimate an impact exposure using a helmet's residual crush depth or volume.

Impairments of memory and learning in older adults exposed to polychlorinated biphenyls via consumption of Great Lakes fish.

An association between in utero polychlorinated biphenyl (PCB) exposure and impaired childhood intellectual functioning has been reported, but the potential impact of PCB exposure during adulthood on intellectual functioning has received little attention. We assessed the impact of PCBs and other fish-borne contaminants on intellectual functioning in older adults. The subjects were 49- to 86-year-old Michigan residents recruited from an existing cohort. Fish eaters ate > 24 lb of sport-caught Lake Michigan fish per year and non-fish eaters ate < 6 lb of Lake Michigan fish per year. A battery of cognitive tests including tests of memory and learning, executive function, and visual-spatial function was administered to 180 subjects (101 fish eaters and 79 non-fish eaters). Blood samples were analyzed for PCBs and 10 other contaminants. We evaluated cognitive outcomes using multiple regression. PCBs and dichlorodiphenyl dichloroethene (DDE) were markedly elevated in fish eaters. After controlling for potential confounders PCB, but not DDE, exposure was associated with lower scores on several measures of memory and learning. These included the Weschler Memory Scale verbal delayed recall (p = 0.001), the semantic cluster ratio (p = 0.006), and list A, trial 1 (p = 0.037), from the California Verbal Learning Test. In contrast, executive and visual-spatial function were not impaired by exposure to either PCBs or DDE. In conclusion, PCB exposure during adulthood was associated with impairments in memory and learning, whereas executive and visual-spatial function were unaffected. These results are consistent with previous research showing an association between in utero PCB exposure and impairments of memory during infancy and childhood.

PCB congener profile in the serum of humans consuming Great Lakes fish.

The State of Michigan has a long history of research into human exposure to environmental contaminants through consumption of recreationally caught fish. A large cohort of Lake Michigan residents who eat fish (fish-eaters) and those who do not eat fish (nonfish-eaters) established in 1980 served as the basis for the congener-specific polychlorinated biphenyl (PCB) exposure evaluation reported here. In this paper we present the serum PCB congener profile for a subset of this cohort who were over 50 years of age. Serum samples were collected in 1993-1995 and were evaluated by a dual column capillary column gas chromatography procedure capable of detecting over 90 PCB congeners. This evaluation demonstrated significant PCB exposure in the fish-eaters (mean serum PCB of 14.26 ppb; n = 101). This elevated exposure allowed the establishment of a detailed profile of the PCB congeners found in humans exposed by this route. Twenty-two congeners of varying concentrations were the most prevalent and constituted over 95% of the total PCB present in most subjects. Four congeners, 138/163 (2,2',3,4,4',5-PCB/2,3,3',4', 5,6-PCB), 180 (2,2',3,4,4',5,5'-PCB), and 153 (2,2',4,4',5,5'-PCB), accounted for 55-64% of the total PCB load. Other congeners, some of toxicologic significance, were also detected by this analytical protocol. Nonfish-eaters had lower total serum PCB levels (mean = 4. 56; n = 78), but the same general pattern of PCB congeners was present. It was demonstrated that careful selection of a subset of prevalent PCB congeners could provide a cost-effective assessment of exposure without losing critical scientific information.

The use of methylphenidate in Michigan.

OBJECTIVE: To describe the epidemiologic findings associated with the use of methylphenidate hydrochloride among children aged 0 to 19 years in Michigan. DESIGN: A population-based data set of all prescriptions filed with the Michigan Triplicate Prescription Program during February and March 1992 was analyzed, maintaining complete anonymity. SETTING: State of Michigan. PARTICIPANTS: All patients receiving a prescription for methylphenidate who are residents of Michigan, and all physicians prescribing methylphenidate. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Descriptive data. RESULTS: Eleven of 1000 Michigan residents between the ages of 0 and 19 years received a prescription for methylphenidate during the study period. Eighty-four percent were boys. Boys aged 10 or 11 years received more prescriptions for methylphenidate than any other age group--43 per 1000. The number of children receiving prescriptions for methylphenidate ranged from 2.5 to 28 per 1000. The range for boys aged 10 or 11 years was from 9.6 to 117 per 1000. Primary care physicians wrote 84% of all prescriptions; pediatricians wrote 59% of the prescriptions for patients younger than 20 years old. Half of the prescriptions written by pediatricians were written by 5% of the pediatricians in the state. CONCLUSIONS: Michigan has been among the states with the highest per capita consumption of methylphenidate for the past 10 years. The major use of methylphenidate is for treatment of attention deficit hyperactivity disorder. The number of boys in Michigan aged 10 or 11 years who were treated with methylphenidate was similar to the national prevalence of the disorder, 3% to 5%. A tenfold variation was noted in the percentage of children medicated when the data were analyzed by county. Relatively few pediatricians account for the largest proportion of prescriptions. Future studies are needed to link the use of methylphenidate with diagnostic and treatment considerations in attention deficit hyperactivity disorder.

Diagnosis of attention-deficit/hyperactivity disorder and use of psychotropic medication in very young children.

CONTEXT: Increases in diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) have elicited public and professional concern. Research suggests that this trend warrants the inclusion of previously underdiagnosed children and adults. It is not clear whether this trend includes young children. OBJECTIVE: To identify patterns of diagnosis and treatment of ADHD in very young children over time. DESIGN: Descriptive study of Michigan Medicaid claims data. PATIENTS: Inclusion criteria included recorded ADHD diagnosis, continuous Medicaid eligibility during a 15-month period, and age 3 years or younger at the first date of service. MAIN OUTCOME MEASURES: Diagnoses of ADHD, conditions commonly comorbid with ADHD, other chronic health conditions, and injuries; treatments such as psychological services and psychotropic medication; and the number of ambulatory visits. RESULTS: We identified 223 children aged 3 years or younger diagnosed with ADHD. Many had conditions commonly comorbid with ADHD (44%), other chronic health conditions (41%), and injuries (40%). More than half received psychotropic medication (57%); fewer received psychological services (27%). Twenty-two different psychotropic medications were used. Patterns included more than 1 psychotropic medication (46%) in 30 combinations of simultaneous use and 44 combinations of sequential use. The mean number of ambulatory visits was 18. CONCLUSIONS: Children aged 3 years or younger had ADHD diagnosed and received markedly variable psychotropic medication regimens. Little information is available to guide these practices. The presence of comorbid conditions and injuries attests to these children's vulnerability. Resources must be identified that will enable physicians to better respond to the compelling needs of these children and their families.

Postsynaptic alpha 1-and alpha 2-adrenoceptor involvement in the vascular responses to neuronally released and exogenous noradrenaline in the hindlimb of the dog and cat.

The contribution of postsynaptic alpha 1-and alpha 2-adrenoceptors to vascular responses was investigated in the blood perfused hindlimbs of pentobarbitone-anaesthetised dogs and chloralose-anaesthetised cats. Responses were obtained to sympathetic nerve stimulation, noradrenaline, phenylephrine and UK-14,304. In the dog and cat hindlimbs, the response to phenylephrine was reduced by the selective alpha 1-adrenoceptor antagonist, prazosin, while that to UK-14,304, in the dog, was reduced by the alpha 2-adrenoceptor antagonist, rauwolscine. Responses to noradrenaline and sympathetic nerve stimulation were only partially blocked by prazosin in both the dog and cat, but were further reduced by the addition of rauwolscine. These results suggest that the hindlimb vasculature of the dog and cat responds to neuronally released, as well as exogenous, noradrenaline by activation of both postsynaptic alpha 1- and alpha 2-adrenoceptors.

A comparison of the effects of lamotrigine on neuroma-induced action potential firing and normal behaviour in rat: implications for establishing a pre-clinical 'therapeutic index'.

The effects of lamotrigine on rat neuroma and behavioural paradigms were evaluated to determine a pre-clinical therapeutic index. Lamotrigine blocked neuroma-induced burst pattern firing at a free plasma concentration of 13.7+/-1.7 microM (n=5). Oral dosing of lamotrigine (50-200 mg/kg) had no significant effects on behaviour but measurements of plasma concentrations of free drug showed non-linear oral absorption and lower than predicted drug levels (5-27 microM). Given intravenously (10-100 mg/kg), lamotrigine did affect behaviour at a free plasma concentration of 42.0 microM (n=2). By comparing free plasma concentrations, a therapeutic index of 3 was calculated, which is lower than published data based on comparing oral doses. We propose that a therapeutic index should only be derived with reference to plasma drug concentrations to prevent non-linear or incomplete drug absorption from confounding accurate estimation.

Computational modeling of ligament mechanics.

This article provides a critical review of past and current techniques for the computational modeling of ligaments and tendons. A brief overview of relevant concepts from the fields of continuum mechanics and finite element analysis is provided. The structure and function of ligaments and tendons are reviewed in detail, with emphasis on the relationship of microstructural tissue features to the continuum mechanical hehavior. Experimental techniques for the material characterization of biological soft tissues are discussed. Past and current efforts related to the constitutive modeling of ligaments and tendons are classified by the particular technique and dimensionality. Applications of one-dimensional and three-dimensional constitutive models in the representation of the mechanical behavior of joints are presented. Future research directions are identified.

Why most workers with occupational repetitive trauma do not file for workers' compensation.

Despite the availability of no fault insurance for wage replacement and medical care costs, the majority of workers diagnosed with an occupational disease do not apply for workers' compensation. The objective of the study was to determine the reasons why workers diagnosed with work-related musculoskeletal disease did not apply for workers' compensation benefits. A cross-sectional study of 1598 individuals diagnosed with neck, upper extremity, and low back work-related musculoskeletal disease from April to June 1996 was performed. All individuals were interviewed over the telephone using a standardized questionnaire. The questionnaire included questions about the precipitating event; demographics; health limitations; mood; pain level; and attitudes toward their health care provider, fellow workers, management, work environment, and filing for workers' compensation. Whenever possible, standardized questions from previous surveys were used. The interviewed individuals with work-related musculoskeletal disease were reported by health care practitioners as required by the state of Michigan's occupational disease reporting law. Workers reported during 12 weeks in the spring of 1996 by a Michigan health care professional as having a neck, back, or upper extremity musculoskeletal disorder were eligible to participate. Among the 2703 reports received, 490 individuals could not be reached, 22 did not speak English, 12 had died or were too incapacitated by other medical conditions, and 581 refused. We interviewed 59% of all eligible workers and 73% of all workers who were reachable and capable of responding in English. Only 25% of workers diagnosed with musculoskeletal disease filed a workers' compensation claim. The factors significantly associated with filing a claim were (1) increased length of employment (> 21 years: odds ratio [OR], 3.01, 95% confidence interval [CI], 1.31 to 6.90); 11 to 20 years: OR, 2.34, 95% CI, 1.01 to 5.47; 6 to 10 years: OR, 1.76, 95% CI, 0.73 to 4.25; 1 to 5 years: OR, 2.36, 95% CI, 1.03 to 5.42; < 1 year: OR, 1.00; (2) lower annual income (< $40,000: OR, 1.75, 95% CI, 1.06 to 2.88 vs > or = $80,000: OR, 1.00); (3) workers' dissatisfaction with coworkers (OR, 1.76, 95% CI, 1.01 to 3.06); (4) physician restrictions on activity (OR, 2.16, 95% CI, 1.55 to 3.00); (5) type of physician providing treatment (specialist, including surgeon or orthopedist: OR, 3.63, 95% CI, 2.37 to 5.55); physical and occupational therapist: OR, 2.15, 95% CI, 1.35 to 3.43); family practitioner: OR, 1.33, 95% CI = 0.89 to 2.01; company physician: OR = 1.00); (6) off work > or = 7 days (OR, 14.85, 95% CI, 10.57 to 20.85); (7) decreased current health status (OR, 0.82, 95% CI, 0.70 to 0.96); and (8) increased severity of illness (OR, 1.24, 95% CI, 1.06 to 20.88). This study showed that only 25% of workers with a work-related musculoskeletal condition filed for workers' compensation and refutes the common perception that an individual with a work-related problem is likely to file a workers' compensation claim. The strongest predictors of who would file were those factors associated with the severity of the condition. Other factors were increasing length of employment, lower annual income, and worker dissatisfaction with coworkers. Our study population consisted mainly of unionized autoworkers, and our findings may not be generalizable to the total workforce.

Evidence-based guidelines for teaching patient-centered interviewing.

In a rare study of effectiveness of an interviewing method, we previously reported a randomized controlled trial demonstrating that training in a step-by-step patient-centered interviewing method improved residents' knowledge, attitudes, and skills and had a consistently positive effect on trained residents' patients. For those who wish to use this evidence-based patient-centered method as a template for their own teaching, we describe here for the first time our training program--and propose that the training can be adapted for students, physicians, nurse practitioners, physician assistants, and other new learners as well. Training was skills-oriented and experiential, fostered positive attitudes towards patient-centered interviewing, and used a learner-centered approach which paid special attention to the teacher-resident relationship and to the resident's self-awareness. Skills training was guided by a newly identified patient-centered interviewing method that described the step-by-step use of specific behaviors.

Screening for congenital dislocation of the hip by physiotherapists. Results of a ten-year study.

We report a prospective study of the feasibility of employing specially trained physiotherapists to screen neonates for congenital dislocation of the hip. During ten years 42,241 babies were screened, using clinical tests; 255 were diagnosed and treated by a Pavlik harness. In the same period 13 children presented late with congenital dislocation of the hip which had not been detected by the screening programme.

The association of serum nonesterified fatty acids and cholesterol, management and feeding practices with peripartum disease in dairy cows.

A prospective study was conducted to determine the relationship of serum nonesterified fatty acids (NEFA) and cholesterol concentrations and herd management practices to the occurrence of metritis, mastitis and retained placenta in Holstein cows in Michigan. Serum samples were collected once prepartum and once postpartum from 257 cows. Animals were under observation for disease occurrence from the date of calving until 3 months postpartum. Metabolic variables used were (1) prepartum only; (2) postpartum only; (3) the NEFA/cholesterol ratio for both pre- and postpartum samples. Management variables included maternity management, feed management, and factors such as season and parity. Multivariable logistic models with random-effect terms to account for the herd effect were used for data analysis. Results showed that: (1) metabolic events associated with energy insufficiency-increased fat mobilization and serum lipoprotein metabolism-were related to increased risk of metritis and retained placenta; (2) higher energy consumption during the last weeks of the dry period might reduce disease risk at parturition; (3) serum NEFA and cholesterol concentrations have potential as indicators of disease risk in dairy cows.

Factors influencing recovery from and duration of lameness in Michigan (USA) horses.

The objective of this study was to identify factors that may affect recovery from and duration of a case of lameness in a stratified random sample of Michigan horses. This was done using data from Phase-II of the Michigan equine monitoring system (MEMS Phase-II), the equine health-monitoring study [Kaneene et al., Prev. Vet. Med. 29 (1997b) 277-292; Ross and Kaneene, Prev. Vet. Med. 28 (1996a) 209-224; Ross and Kaneene, Prev. Vet. Med. 29 (1996b) 59-75; Ross et al., Am. J. Vet. Res. 59 (1997) 23-29]. In this study, statistical modelling was conducted to evaluate risk factors affecting recovery from and duration of lameness using multivariable logistic regression and Cox's proportional hazards regression, respectively. Of 357 incident lameness cases reported during MEMS Phase-II, 280 (78.6%) were reported to have recovered. The median duration of a lameness case was 18 days (1st quartile (Q): 1, maximum (Max): 360). A total of 296 of 357 (82.9%) incident lameness cases received some type of treatment. Of 619 total treatments used, 329 (53.2%) were administered, conducted or applied by a veterinarian. Horses experiencing other types of lameness were less likely to recover than those experiencing hoof lameness (odds ratio (OR) = 0.48; 95% CI: 0.25, 0.93). Horses that had participated in exercise-related activities during the study period and prior to the lameness were more likely to recover (OR = 1.91; 95% CI: 1.05, 3.50). Treatment of the lameness was associated with an increased likelihood of recovery (OR = 1.82; 95% CI: 0.97, 3.45). Cases with a veterinarian involved in the diagnosis were associated with a decreased risk of recovery (OR = 0.48; 95% CI: 0.27, 0.84) and a longer duration lameness (HR = 0.58; 95% CI: 0.45, 0.73)--which might indicate that these cases were more complex or severe. Although cases treated for lameness were more likely to recover (OR = 1.82; 95% CI: 1.05, 3.50), treatment was not associated with lameness duration (HR = 0.58; 95% CI: 0.45, 0.73).

The effect of subclinical Mycobacterium paratuberculosis infection on days open in Michigan, USA, dairy cows.

A prospective cohort study design was used to evaluate the impact of subclinical Mycobacterium paratuberculosis infection on days open in a sample of Michigan dairy herds with a history of cows positive for M. paratuberculosis diagnosed by fecal culture. Participating herds were tested and productivity and reproduction records were monitored for 18 months. All cows > or = 24 months old were tested for M. paratuberculosis infection using the ELISA and radiometric fecal-culture (RFC) techniques. Test-negative cows were re-tested at the conclusion of the monitoring period. Multivariable regression models were used. Using both tests in parallel, the overall sample apparent prevalence for M. paratuberculosis infection was 41.8% (223/533 animals tested). Adjusting for diagnostic sensitivity and specificity, this resulted in a calculated sample true prevalence of 59.9%. ELISA-positive cows (on average) had a 28-day increase in days open when compared to ELISA-negative cows (p=0.02). The diagnostic method used to define a case altered the apparent association between paratuberculosis test status and days open. Fecal culture was a less-effective diagnostic tool for use in herds with a high prevalence of infected animals. The increase in days open in the ELISA-positive cows was an indication that perhaps reduced estrus expression or an increased post-partum anestrous period occurred in the subclinically infected ELISA-positive animals. This might have been due to a negative energy balance associated with M. paratuberculosis infection.

Skin cancer prevention and detection practices in a Michigan farm population following an educational intervention.

Farmers face an increased risk of skin cancer, presumed to be secondary to their increased occupational exposure to sunlight. This study examines skin cancer prevention and detection beliefs and practices among adult farmers in defined control and comparison farming communities in four contiguous counties of Michigan, before and after a community-based educational intervention. The educational intervention included mailing packets containing information on skin cancer risks and community sources for screening, disseminating articles in local newspapers on skin cancer prevention and control measures, and providing information and screening at local county fairs and agricultural community fairs. The responses of 2,999 survey participants were analyzed to identify the interrelationships among their beliefs and their descriptions of their (primary preventive) self-care and professional medical care seeking (for detection and treatment) practices. Factors associated with the likelihood of skin cancer screening and with measures of knowledge and practices associated with medical care of skin cancer were examined. The intervention appeared to improve the practice of preventive behaviors and seeking medical care.

Survival analysis of risk factors associated with the occurrence of lameness in a Michigan horse population.

OBJECTIVE: To evaluate the associations of operation and individual animal-level risk factors with occurrence of lameness in the Michigan horse population. SAMPLE POPULATION: 3,925 horses monitored from 138 randomly selected Michigan operations for a total of 814,753 horse-days. PROCEDURE: All horses monitored < 60 days were eliminated from the source population. From the remaining horses, a prospective unmatched case-control study population was generated that included all cases and a random sample of noncases. Analysis of risk factors associated with occurrence of lameness was conducted, using Cox's proportional hazards regression model. RESULTS: Horses in larger operations, compared with horses in the first operation size quartile, were associated with decreased risk of lameness (2nd quartile [Q]: hazard ratio [HR] = 0.57; 95% confidence interval [CI]: 0.36, 0.91; 3rd Q: HR = 0.74; 95% CI: 0.49, 1.13; 4th Q: HR = 0.46; 95% CI: 0.28, 0.76). Compared with mares, stallions (HR = 1.90; 95% CI: 1.17, 3.07) and geldings (HR = 1.46; 95% CI: 1.02, 2.09) were at increased risk of lameness. Compared with horses used for breeding purposes only, those participating in exercise or performance-related activities including racing (HR = 4.70; 95% CI: 1.70, 13.03) and showing (HR = 2.80; 95% CI: 1.07, 7.28) also were at increased risk of lameness. CONCLUSIONS: Comparison of these results with those conducted using multivariable logistic regression strengthens the argument that there is decreased risk of lameness for horses in larger operations and increased risk of lameness for active horses. Additionally, results of this analysis suggested that stallions and geldings are at increased risk of lameness, compared with mares. CLINICAL RELEVANCE: Lameness prevention strategies in the horse industry should focus principally on horses participating in exercise or performance-related activities, including racing and showing, on male horses, and on horses stabled in smaller operations.