Should regression calibration or multiple imputation be used when calibrating different devices in a longitudinal study?

In longitudinal studies, the devices used to measure exposures can change from visit to visit. Calibration studies, wherein a subset of participants is measured using both devices at follow-up, may be used to assess between-device differences (i.e., errors). Then, statistical methods are needed to adjust for between-device differences and the missing measurement data that often appear in calibration studies. Regression calibration and multiple imputation are two possible methods. We compared both methods in linear regression with a simulation study, considering various real-world scenarios for a longitudinal study of pulse wave velocity. Regression calibration and multiple imputation were both essentially unbiased, but correctly estimating the standard errors posed challenges. Multiple imputation with predicted mean matching produced close agreement with the empirical standard error. Fully stochastic multiple imputation underestimated the standard error by up to 50%, and regression calibration with bootstrapped standard errors performed slightly better than fully stochastic multiple imputation. Regression calibration was slightly more efficient than either multiple imputation method. The results suggest use of multiple imputation with predictive mean matching over fully stochastic imputation or regression calibration in longitudinal studies where a new device at follow-up might be error-prone compared to the device used at baseline.

Making Sense of Censored Covariates: Statistical Methods for Studies of Huntington's Disease.

The landscape of survival analysis is constantly being revolutionized to answer biomedical challenges, most recently the statistical challenge of censored covariates rather than outcomes. There are many promising strategies to tackle censored covariates, including weighting, imputation, maximum likelihood, and Bayesian methods. Still, this is a relatively fresh area of research, different from the areas of censored outcomes (i.e., survival analysis) or missing covariates. In this review, we discuss the unique statistical challenges encountered when handling censored covariates and provide an in-depth review of existing methods designed to address those challenges. We emphasize each method's relative strengths and weaknesses, providing recommendations to help investigators pinpoint the best approach to handling censored covariates in their data.

A lateral approach allows accurate and stable total elbow replacement in dogs.

OBJECTIVE: Evaluate whether total elbow replacement (TER) through a lateral approach is accurate and stable. ANIMALS: 12 skeletally mature large-breed dog cadavers were used. METHODS: Limb alignment, elbow joint motion, and collateral ligament laxity were evaluated preoperatively. The order of surgery (left or right) and the approach (lateral or medial) were randomly selected for TER in each dog. The other approach was used in the contralateral elbow. Intraoperative technical difficulties, duration of surgery, and anatomic complications were recorded. Limb alignment, elbow joint motion, collateral ligament laxity, and prosthetic component alignment were evaluated after surgery. Data were collected from June 11 to 15, 2023. RESULTS: The duration of surgery using a lateral or medial approach did not differ (P = .499). Anatomic complications were not observed. The lateral approach resulted in 8° more elbow extension (P = .003), 1.58° less lateral collateral ligament constraint (P = .033), 2.80° less medial collateral ligament constraint (P = .002), 4.38° less frontal plane constraint (P = .004), 8° greater humeral component inclination (P = .033), and 5.6° greater radioulnar component varus (P = .001) than the medial approach. Varus of the radius, mechanical axis deviation, limb supination, elbow flexion, mediolateral humeral component and craniocaudal radioulnar component orientation did not differ among joints operated using a lateral or medial approach. In normal cadaveric elbows, a lateral approach for TER appears feasible, producing equivalent limb alignment, joint laxity, and joint motion to normal elbows and to TER placed using a medial approach. CLINICAL RELEVANCE: In dogs, TER can be performed using a lateral surgical approach.

Association Between Hypertensive Disorders of Pregnancy and Interval Neurocognitive Decline: An Analysis of the Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are associated with cognitive decline later in life among U.S. Hispanic/Latina individuals. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a prospective population-based study of Hispanic/Latino individuals aged 18-74 years from four U.S. communities. This analysis included parous individuals aged 45 years or older who participated in the HCHS/SOL clinic study visit 1 (2008-2011) neurocognitive assessment and subsequently completed a repeat neurocognitive assessment as part of the Study of Latinos-Investigation of Neurocognitive Aging ancillary study visit 2 (2015-2018). Hypertensive disorders of pregnancy were assessed retrospectively by self-report of any gestational hypertension, preeclampsia, or eclampsia. Cognitive functioning was measured at both study visits with the Brief Spanish-English Verbal Learning Test, Digit Symbol Substitution, and Word Fluency. A regression-based approach was used to define cognitive decline at visit 2 as a function of cognition at visit 1 after adjustment for age, education, and follow-up time. Linear regression models were used to determine whether hypertensive disorders of pregnancy or their component diagnoses were associated with standardized cognitive decline after adjustment for sociodemographic characteristics, clinical and behavioral risk factors, and follow-up time. RESULTS: Among 3,554 individuals included in analysis, the mean age was 56.2 years, and 467 of individuals (13.4%) reported at least one hypertensive disorder of pregnancy. Individuals with hypertensive disorders of pregnancy compared with those without were more likely to have higher mean systolic blood pressure, fasting glucose, and body mass index. After an average of 7 years of follow-up, in fully adjusted models, gestational hypertension was associated with a 0.17-SD relative decline in Digit Symbol Substitution scores (95% CI, -0.31 to -0.04) but not other cognitive domains (Brief Spanish-English Verbal Learning Test or Word Fluency). Neither preeclampsia nor eclampsia was associated with neurocognitive differences. CONCLUSION: The presence of preeclampsia or eclampsia was not associated with interval neurocognitive decline. In this cohort of U.S. Hispanic/Latina individuals, gestational hypertension alone was associated with decreased processing speed and executive functioning later in life.

Kinematic performance of a novel temporomandibular joint replacement prosthesis under bite-force conditions in dogs and cats.

OBJECTIVE: To evaluate the kinematics and stability of the temporomandibular joint (TMJ) of cats and dogs with and without a TMJ replacement (TMJR) prosthesis under simulated bite forces and mouth opening. ANIMALS: Sixteen cadaver skulls from domestic cats (n = 8) and medium- to large-breed dogs (n = 8). METHODS: Intact TMJs were tested. Following condylectomy and coronoidectomy, the skulls were fitted with a TMJR prosthesis unilaterally and retested. Prosthesis was similarly implanted in the contralateral TMJ in 4 cats and 4 dogs before retesting. Left and right bite motions were evaluated before bite contact to peak bite force (200 N in dogs, 63 N in cats). Mouth opening motion was recorded. Mandibular displacement under load was evaluated in 3 orthogonal planes. Maximal displacement was compared between TMJR groups and native TMJ. Prosthesis-bone motion of the temporal and mandibular components was evaluated during simulated bites and mouth opening. RESULTS: TMJR resulted in joint motion not demonstrably different from the native TMJ, with the ability to fully open and close the mouth and with minimal laterotrusion. The TMJR prosthesis demonstrated similar stability after unilateral and bilateral replacement during bite force and with an open mouth. Mean implant-bone motion during bite simulations for the temporal and mandibular TMJR components was ≤ 60 µm in cats and ≤ 30 µm in dogs. CLINICAL RELEVANCE: A novel TMJR can be implanted and allows normal jaw motion. Joint stability is maintained after TMJR implantation in the TMJ of dogs and cats TMJ that is devoid of muscular support.

Nonalcoholic Fatty Liver Disease and Longitudinal Change in Imaging and Plasma Biomarkers of Alzheimer Disease and Vascular Pathology.

BACKGROUND AND OBJECTIVES: Prospective measures of plasma and cerebral MRI biomarkers of Alzheimer disease (AD) and vascular neuropathology provide an opportunity to investigate possible mechanisms linking liver disease and dementia. We aimed to quantify the association of midlife nonalcoholic fatty liver disease (NAFLD) with change in plasma and brain MRI biomarkers of AD and vascular neuropathology. METHODS: We included participants from the Atherosclerosis Risk in Communities Study with brain MRI measurements of white matter hyperintensity (WMH) volume and temporal-parietal lobe cortical thickness meta region of interest (ROI) at up to 2 different visits, in 2011-13 and 2016-19, and plasma biomarkers of ß-amyloid (Aß)42:40, phosphorylated tau at threonine 181, and neurofilament light (NfL) were measured up to 3 times in 1993-95, 2011-13, and 2016-19. NAFLD was categorized using the fatty liver index in 1990-92. Multivariate linear regression was performed for associations between midlife NAFLD and change in plasma and brain MRI biomarkers of AD and vascular neuropathology. The primary models adjusted for demographics, Apolipoprotein E, alcohol use, and kidney function. RESULTS: Among 1,706 participants (mean age 56 years, 62% female, 28% Black), midlife NAFLD vs no NAFLD was associated with greater late-life WMH volume (difference per SD 0.19, 95% CI 0.06-0.31) and faster late-life WMH increase over 6 years (difference in annual change, SD 0.28, 95% CI 0.05-0.51), suggesting accumulating vascular pathology. Midlife NAFLD vs no NAFLD was also associated with AD biomarkers in midlife (lower Aß42:40 [SD -0.21, 95% CI -0.39 to -0.04] measured in 1993-95) and late life (lower Aß42:40 [SD -0.13, 95% CI -0.23 to -0.03] and lower temporal-parietal lobe cortical thickness meta ROI [SD -0.16, 95% CI -0.28 to -0.05] measured in 2011-13). Although midlife NfL was lower in individuals with vs without midlife NAFLD, those with NAFLD exhibited a faster rate of NfL increase that accelerated over time. DISCUSSION: Midlife NAFLD shows associations with AD and accumulating vascular pathology, revealing potential pathways linking liver function to dementia. Plasma biomarkers of neuropathology and neuronal injury may serve as easily measurable and dynamic indicators for monitoring the impacts of impaired liver function on brain health.

K-wire is more damaging than standard or acrylic drill bits when evaluating torsional properties of rabbit (Oryctolagus cuniculi) femurs.

OBJECTIVE: The objective of this study is to compare drilling variables and torsional mechanical properties of rabbit femora after bicortical drilling with a 1.5-mm standard surgical drill bit, acrylic drill bit, and K-wire. SAMPLES: 24 pairs of rabbit femora. METHODS: After drilling under controlled axial displacement rate, each bone was biaxially loaded in compression followed by rapid external torsion to failure. Maximum axial thrust force, maximum drill torque, integral of force and displacement, change in temperature, maximum power spectral density of the torque signal, torque vibration, and torque and angle at the yield and failure points were collected. Pre- and postyield stiffness, yield and failure energies, and postyield energy were calculated. RESULTS: The work required to drill through the cis- and transcortices (integral of force and displacement) was greater for the K-wire, followed by the acrylic and then standard drill bits, respectively. The K-wire demonstrated higher maximum torque than the drill bits at the ciscortex, and the force of drilling was significantly greater. The vibration data was greater with the acrylic and standard drill bits than the K-wire. There was no difference in torsional strength between drilling types. CLINICAL RELEVANCE: Mechanical differences exist between different drill bits and K-wire and demonstrate that the K-wire is overall more damaging than the surgical drill bit.

Liver integrity and the risk of Alzheimer's disease and related dementias.

INTRODUCTION: We examined midlife (1990-1992, mean age 57) and late-life (2011-2013, mean age 75) nonalcoholic fatty liver disease (NAFLD) and aminotransferase with incident dementia risk through 2019 in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: We characterized NAFLD using the fatty liver index and fibrosis-4, and we categorized aminotransferase using the optimal equal-hazard ratio (HR) approach. We estimated HRs for incident dementia ascertained from multiple data sources. RESULTS: Adjusted for demographics, alcohol consumption, and kidney function, individuals with low, intermediate, and high liver fibrosis in midlife (HRs: 1.45, 1.40, and 2.25, respectively), but not at older age, had higher dementia risks than individuals without fatty liver. A U-shaped association was observed for alanine aminotransferase with dementia risk, which was more pronounced in late-life assessment. DISCUSSION: Our findings highlight dementia burden in high-prevalent NAFLD and the important feature of late-life aminotransaminase as a surrogate biomarker linking liver hypometabolism to dementia. Highlights Although evidence of liver involvement in dementia development has been documented in animal studies, the evidence in humans is limited. Midlife NAFLD raised dementia risk proportionate to severity. Late-life NAFLD was not associated with a high risk of dementia. Low alanine aminotransferase was associated with an elevated dementia risk, especially when measured in late life.

Ex vivo biomechanical evaluation of an adhered fiberglass and polymethyl methacrylate sole-hoof wall cast on stabilization of type III distal phalanx fractures under simulated physiologic midstance loads.

OBJECTIVE: To evaluate the effect of the application of a novel fiberglass-glue cast (FGC) on the fracture gap width in experimentally created type III distal phalanx fractures in cadaveric specimens under simulated physiologic loads. STUDY DESIGN: Ex vivo biomechanical laboratory study. ANIMALS: Nine unilateral adult equine cadaver forelimbs. METHODS: Type III distal phalanx fractures were created in forelimb specimens, which maintained distal components of the passive stay apparatus. The fracture gap was measured at 5%, 20%, 25%, 50%, 75%, and 95% of fracture length (palmar articular border to solar margin) using D65Pr-PaDiO radiographs. The limb was axially loaded (700, 3600, 4600, and 6700 N) before, during, and after removal of a woven fiberglass cloth and polymethyl methacrylate cast that encompassed the sole and distal portion of the hoof wall (FGC). Fracture gap widths were compared among loads and treatments using a mixed model ANOVA. RESULTS: On average, under simulated physiological midstance loads, the fracture gap width was 0.2 mm smaller after FGC application, with the greatest decrease (0.5 mm) near the articular surface. On average, it was 0.3 mm smaller than after FGC removal. Fracture gap width was 0.1 mm greater when midstance loads transitioned from standing load to walking, trotting, and gallop loads. The fracture gap width increased by 1.3 mm with increasing distance from the articular surface. CONCLUSION: The FGC reduced the fracture gap width and prevented the fracture gap widening that occurred after FGC removal. CLINICAL SIGNIFICANCE: The findings support consideration of FGC use in the treatment of horses with type III distal phalangeal fractures.

Associations between avocado intake and measures of glucose and insulin homeostasis in Hispanic individuals with and without type 2 diabetes: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND AND AIMS: To investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry. METHODS AND RESULTS: The associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%ß), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by dysglycemia status. In those with normoglycemia, avocado intake was associated with a higher insulinogenic index (ß = 0.17 ± 0.07, P = 0.02). In those with T2D (treated and untreated), avocado intake was associated with lower hemoglobin A1c (HbA1c; ß = -0.36 ± 0.21, P = 0.02), and lower fasting glucose (ß = -0.27 ± 0.12, P = 0.02). In the those with untreated T2D, avocado intake was additionally associated with HOMA-%ß (ß = 0.39 ± 0.19, P = 0.04), higher insulin values 2-h after an oral glucose load (ß = 0.62 ± 0.23, P = 0.01), and a higher insulinogenic index (ß = 0.42 ± 0.18, P = 0.02). No associations were observed in participants with prediabetes. CONCLUSIONS: We observed an association of avocado intake with better glucose/insulin homeostasis, especially in those with T2D.

Hoof Expansion, Deformation, and Surface Strains Vary with Horseshoe Nail Positions.

Racehorses are susceptible to underrun heel hoof conformation. Racehorses are often shod with nails placed toward the heel. It is unknown if palmar nails restrict or alter hoof deformation in a manner that could promote the development of underrun heel conformation over time with repeated loading. To determine how the addition of palmar nails affects heel deformation during limb loading, hoof expansion and hoof wall deformations were quantified using rosette strain gauges and kinematic markers during in the vitro limb loading of cadaveric limbs that simulated midstance for walk, trot, and canter loads. Nail treatments used to attach a horseshoe to the hoof included: toe nails (T), toe and quarter nails (TQ), and toe, quarter, and heel nails (TQH). The effects of nail treatment on heel expansion and hoof wall deformations were assessed using repeated measures analysis of variance (p < 0.05). Nails placed palmar to the quarters of the hoof decreased heel expansion (p < 0.001). Heel nails resulted in the largest changes in hoof wall principal strain directions distally. The application of nails palmar to the hoof quarters alters hoof wall deformation during limb loading. The continued loading of the hoof with palmer nails could alter hoof conformation over time.

Biomechanical Performance of Biodegradable Screw Fixation in Mandibular Distraction Osteogenesis.

Internal distraction devices are commonly used in congenital micrognathia. The eventual need for device and screw removal can be challenging, requiring extensive dissection and disturbance of bone regenerate. Bioabsorbable poly-L-lactide (PLLA) screws, compared to traditional titanium screws, simplify device removal. Previous in vivo studies have found that the maximal compressive force generated by mandibular distraction is 69.4N. We hypothesized that PLLA screws could support these compressive/distraction forces. Ten mandibles were obtained from 5 canine cadavers. Paired mandibles from the same cadaver were each fixated to a mandibular distractor with eight screws (either titanium or PLLA). Devices were each set to 15 and 30 mm of distraction distance. Compression force of 80 N was then generated parallel to the axis of the distraction device. Distractor displacement was measured to detect any mechanical failure during this pre-set load. Finally, if no failure was observed at 80 N, a load-to-failure compression test was done in the PLLA group to determine the mechanical failure point. All distractors in both the titanium and PLLA screw groups withstood 80 N of compression without failure. When the load-to-failure test was performed in the PLLA group, the average device failure point was 172.8 N (range 148-196 N). Review of high-frame-rate video demonstrated that all failures occurred due to the PLLA screws breaking or falling out. Bioabsorbable PLLA screws can withstand compressive forces more than double that of the maximal in vivo forces needed during mandibular distraction. These screws may be an acceptable alternative for the fixation of internal mandibular distractors.

Effects of Jumping Phase, Leading Limb, and Arena Surface Type on Forelimb Hoof Movement.

During the stance phase of equine locomotion, ground reaction forces are exerted on the hoof, leading first to rapid deceleration ("braking") and later to acceleration ("propulsion") as the hoof leaves the ground. Excessive hoof deceleration has been identified as a risk factor for musculoskeletal injury and may be influenced by arena surface properties. Therefore, our objective was to evaluate the effect of arena surface type (dirt, synthetic) on hoof translation of the leading and trailing forelimbs during jump takeoff and landing. Solar hoof angle, displacement, velocity, and deceleration were captured using kinematic markers and high-speed video for four horses jumping over a 1.1 m oxer at 12 different arenas (5 dirt, 7 synthetic). Surface vertical impact and horizontal shear properties were measured simultaneously. The effects of surface type (dirt, synthetic), jump phase (takeoff, landing), and limb (leading, trailing) on hoof movement were assessed using ANOVA (p < 0.05), while the relationships of hoof movement with surface mechanical properties were examined with correlation. Slide time (p = 0.032), horizontal velocity of the hoof (p < 0.001), and deceleration (p < 0.001) were greater in the leading limb, suggesting a higher risk of injury to the leading limb when braking. However, surface type and jump phase did not significantly affect deceleration during braking.

Biomechanical comparison of compact versus standard flute drill bits, and interlocking versus buttress thread self-tapping cortical bone screws in cadaveric equine third metacarpal condyle.

OBJECTIVES: To compare (1) performance of compact versus standard flute drill bits, (2) screw insertion properties and (3) pullout variables between interlocking thread (ITS) and buttress thread (BTS) self-tapping screws in third metacarpi. STUDY DESIGN: In vitro experimental study. SAMPLE POPULATION: Paired third metacarpi from 11 Thoroughbreds aged 2-4 years. METHODS: Screws were inserted into the lateral condylar fossae following bone preparation using the respective drill bit for each screw type. Screw pullout was achieved using a mechanical testing system. Density and porosity of bone surrounding screw holes was measured with microcomputed tomography following each pullout test. Drilling, screw insertion and pullout variables were compared between drill bit and screw types using repeated measures ANOVA. Linear regression analyses were used to characterize relationships between bone tissue properties and drill bit and screw outcomes. RESULTS: Maximum torque power spectral density (PSD) was lower for compact flute drill bits. Insertion torque was 50% higher for ITS. BTS had 33% greater preyield stiffness and 7% greater mean yield force. Bone tissue properties affected measured variables similarly for both screw and drill bit types. CONCLUSIONS: Lower torque PSD may increase durability of the compact flute drill bit. ITS had greater insertional torque, which may reflect greater bone engagement. BTS had greater resistance to axial pullout forces. CLINICAL SIGNIFICANCE: Metacarpal bone provides a simple model for comparison of drill bit and screw designs. Use of ITS to repair equine fractures subject to predominantly tensile forces is not justified based on the results of this study.

FGF4L2 retrogene copy number is associated with intervertebral disc calcification and vertebral geometry in Nova Scotia Duck Tolling Retrievers.

OBJECTIVES: To evaluate the effects of the chondrodystrophy-associated FGF4L2 retrogene on intervertebral disc (IVD) calcification and vertebral geometry. ANIMALS: 22 Nova Scotia Duck Tolling Retrievers (NSDTR) with no FGF4L2 retrogene (n = 7, wild-type dogs), 1 retrogene copy (8, heterozygous dogs), or 2 retrogene copies (7, homozygous dogs). PROCEDURES: Computed tomography (CT) scans of the vertebral column were analyzed using computer-aided design (CAD) software. IVD calcification, vertebral column length, and vertebral geometry of the third cervical (C3), 13th thoracic (T13), and first lumbar (L1) vertebrae were compared. RESULTS: IVD calcification was not found in wild-type dogs. IVD calcification was more frequent in homozygous dogs than heterozygous (P = .008) or wild-type dogs (P < .001) and in heterozygous dogs compared to wild-type dogs (P < .001). Four IVDs were subclinically herniated in 3 dogs (2 homozygous, 1 heterozygous). Calcified IVD had a greater volume and surface area in heterozygous dogs than homozygous dogs. C3 vertebral canal height-to-width ratio was greater in homozygous dogs than heterozygous dogs (P = .044) and wild-type dogs (P = .010). CLINICAL RELEVANCE: IVD calcification and vertebral geometry can be analyzed using CAD software. The presence of 1 or 2 FGF4L2 copies in the absence of the FGF4L1 retrogene has an additive effect on the number of calcified IVD and a minor effect on vertebral geometry in NSDTR dogs. Data support the use of FGF4L2 phenotyping to reduce clinical disease in segregating breeds and to monitor the introduction of wild-type alleles into fixed breed populations.

Metal reactivity is present in dogs with tibial plateau leveling osteotomy and total hip replacement implants.

OBJECTIVE: Determine whether dogs with well-functioning orthopedic metal implants can develop metal reactivity. SAMPLE: Client-owned dogs that had tibial plateau leveling osteotomy (TPLO) or total hip replacement (THR) implants for 12 months or more and control dogs with no implants. PROCEDURES: Lymphocyte transformation testing was performed by exposing peripheral blood lymphocytes to nickel (Ni), chromium (Cr), cobalt (Co), or a combination of these metals. Lymphocyte proliferation was assessed with flow cytometry. Lymphocyte stimulation indexes (SIs) were calculated. A SI > 2 was considered reactive. Median SIs of dogs in response to metal exposure were compared statistically. RESULTS: Samples from 10 dogs with TPLO, 12 dogs with THR, and 7 control dogs were analyzed. Six dogs out of 22 with metal implants had a reactive SI to 1 or more metals, while 2 of 7 control dogs had a SI > 2 when exposed to nickel only. When all metals were considered, no differences in metal reactivity were found between TPLO, THR, and control groups. CLINICAL RELEVANCE: Metal reactivity is present in dogs and can be identified using lymphocyte transformation testing. Reactivity to Ni is present in dogs with and without metal implants. Reactivity to Co and Cr occurs in some dogs with metal implants.

Long-Term Assessment of Bone Regeneration in Nonunion Fractures Treated with Compression-Resistant Matrix and Recombinant Human Bone Morphogenetic Protein-2 in Dogs.

OBJECTIVE: The aim of this study was to assess bone density, bone architecture and clinical function of canine nonunion distal appendicular long bone fractures with a defect treated with fixation, compression-resistant matrix and recombinant human bone morphogenetic protein-2 (rhBMP-2). STUDY DESIGN: Prospective cohort study with dogs at least 1-year post treatment. Computed tomography was performed and quantitative measurements from previous fracture sites were compared with measurements from contralateral limbs. Subjective evaluation included gait assessment and palpation. RESULTS: Six patients met the inclusion criteria. The rhBMP-2 treated bone exhibited higher density at the periphery and lower density in the centre, similar to the contralateral limb. All patients were weight bearing on the treated limb and all fractures were healed. CONCLUSION: The rhBMP-2-treated bone underwent restoration of normal architecture and density. Acceptable limb function was present in all patients. The results of this study can serve as a basis for long-term response in treating nonunion fractures in veterinary patients.

Stifle joint osteoarthritis in small-breed and medium-breed dogs is more severe after cranial cruciate ligament injury than medial patellar luxation.

This retrospective observational study aimed to characterize the severity and distribution of OA in the stifle joints of small and medium dogs with CCL injury and/or MPL. Radiographs of the stifle joints from 218 dogs from 10 small and medium breeds were included; 127 joints had CCL injury, 76 joints had MPL, and 73 joints had CCL injury and MPL. OA was graded at 33 sites within the joint. The mean ± SD OA score was 20.3 ± 9.9. For all joints, OA was more severe in heavier than lighter dogs (P = 0.003). Joints with MPL (14.9 ± 8.2) had lower OA scores than joints with CCL injury (22.2 ± 10.0, P = 0.003) or CCL injury and MPL (22.6 ± 9.4, P < 0.001). OA scores were higher in joints with MPL for older dogs (r = 0.408, P < 0.001) but did not change with age in joints with CCL injury. The pattern of OA did not differ among joints with CCL injury or MPL. The retrospective nature of the study limited findings to associations but did not allow conclusions regarding factors causing OA or enhancing its progression. We concluded that, in small- and medium-breed dogs, the patterns of stifle OA joint after CCL injury and MPL are similar. Radiographic OA after CCL injury is more severe than MPL. An increase in age leads to an increase in OA at the time of presentation at a referral hospital in stifle joints with MPL and without CCL injury.

Genetic associations between sleep traits and cognitive ageing outcomes in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Sleep phenotypes have been reported to be associated with cognitive ageing outcomes. However, there is limited research using genetic variants as proxies for sleep traits to study their associations. We estimated associations between Polygenic Risk Scores (PRSs) for sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnoea (OSA) and measures of cogntive ageing in Hispanic/Latino adults. METHODS: We used summary statistics from published genome-wide association studies to construct PRSs representing the genetic basis of each sleep trait, then we studied the association of the PRSs of the sleep phenotypes with cognitive outcomes in the Hispanic Community Healthy Study/Study of Latinos. The primary model adjusted for age, sex, study centre, and measures of genetic ancestry. Associations are highlighted if their p-value <0.05. FINDINGS: Higher PRS for insomnia was associated with lower global cognitive function and higher risk of mild cognitive impairment (MCI) (OR = 1.20, 95% CI [1.06, 1.36]). Higher PRS for daytime sleepiness was also associated with increased MCI risk (OR = 1.14, 95% CI [1.02, 1.28]). Sleep duration PRS was associated with reduced MCI risk among short and normal sleepers, while among long sleepers it was associated with reduced global cognitive function and with increased MCI risk (OR = 1.40, 95% CI [1.10, 1.78]). Furthermore, adjustment of analyses for the measured sleep phenotypes and APOE-ε4 allele had minor effects on the PRS associations with the cognitive outcomes. INTERPRETATION: Genetic measures underlying insomnia, daytime sleepiness, and sleep duration are associated with MCI risk. Genetic and self-reported sleep duration interact in their effect on MCI. FUNDING: Described in Acknowledgments.

Association of neighborhood segregation with 6-year incidence of metabolic syndrome in the Hispanic community health study/study of Latinos.

PURPOSE: Examine the association between neighborhood segregation and 6-year incident metabolic syndrome (MetSyn) in the Hispanic Community Health Study/Study of Latinos. METHODS: Prospective cohort of adults residing in Miami, Chicago, the Bronx, and San Diego. The analytic sample included 6,710 participants who did not have MetSyn at baseline. The evenness and exposure dimensions of neighborhood segregation, based on the Gini and Isolation indices, respectively, were categorized into quintiles (Q). Racialized economic concentration was measured with the Index of Concentration at the Extremes (continuously and Q). RESULTS: Exposure, but not evenness, was associated with higher disease odds (Q1 (lower segregation) vs. Q4, OR = 1.53, 95% CI = 1.082.17; Q5, OR = 2.29, 95% CI = 1.493.52). Economic concentrationprivilege (continuous OR = 0.87, 95% CI = 0.770.98), racial concentrationracialized privilege (Q1 (greater concentration) vs. Q2 OR = 0.75, 95% CI = 0.541.04; Q3 OR = 0.68, 95% CI = 0.441.05; Q4 OR = 0.68, 95% CI = 0.451.01; Q5 OR = 0.64, 95% CI = 0.420.98)(continuous OR = 0.93, 95% CI = 0.821.04), and racialized economic concentrationprivilege (i.e., higher SES non-Hispanic White, continuous OR = 0.86, 95% CI = 0.760.98) were associated with lower disease odds. CONCLUSION: Hispanics/Latino adults residing in neighborhoods with high segregation had higher risk of incident MetSyn compared to those residing in neighborhoods with low segregation. Research is needed to identify the mechanisms that link segregation to poor metabolic health.