Development and validation of a sleep questionnaire, SNoRE 3.0, to evaluate sleep in companion dogs.

Disturbances in the sleep-wake cycle are a debilitating, yet rather common condition not only in humans, but also in family dogs. While there is an emerging need for easy-to-use tools to document sleep alterations (in order to ultimately treat and/or prevent them), the veterinary tools which yield objective data (e.g. polysomnography, activity monitors) are both labor intensive and expensive. In this study, we developed a modified version of a previously used sleep questionnaire (SNoRE) and determined criterion validity in companion dogs against polysomnography and physical activity monitors (PAMs). Since a negative correlation between sleep time and cognitive performance in senior dogs has been demonstrated, we evaluated the correlation between the SNoRE scores and the Canine Dementia Scale (CADES, which includes a factor concerning sleep). There was a significant correlation between SNoRE 3.0 questionnaire scores and polysomnography data (latency to NREM sleep, ρ = 0.507, p < 0.001) as well as PAMs' data (activity between 1:00 and 3:00 AM, p < 0.05). There was a moderate positive correlation between the SNoRE 3.0 scores and the CADES scores (ρ = 0.625, p < 0.001). Additionally, the questionnaire structure was validated by a confirmatory factor analysis, and it also showed an adequate test-retest reliability. In conclusion the present paper describes a valid and reliable questionnaire tool, that can be used as a cost-effective way to monitor dog sleep in clinical settings.

A large West Antarctic Ice Sheet explains early Neogene sea-level amplitude.

Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records1-3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth2. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene4,5. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72-17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution.

Questionnaire-based Analysis of Owner-reported Scratching and Pain Signs in Cavalier King Charles Spaniels Screened for Chiari-like Malformation and Syringomyelia.

BACKGROUND: Chiari-like malformation (CM) and syringomyelia (SM) cause a pain syndrome in Cavalier King Charles spaniels (CKCS). Clinical signs are not consistently apparent on neurologic examination, and owner reporting of signs provides vital clinical history. However, owner questionnaires for this disease are not well developed. OBJECTIVES: To develop a tool to capture owner-reported clinical signs for use in clinical trials and to compare owner-reported signs with the presence of pain on neurologic examination and SM on magnetic resonance imaging (MRI). ANIMALS: Fifty client-owned CKCS. METHODS: Owners completed a questionnaire and pain/scratch map. Each dog underwent a neurologic examination and craniocervical magnetic resonance imaging (MRI). Questionnaire responses were developed into scores, area of shading for pain/scratch maps was measured, and consistency of responses between these tools was assessed. Owner-reported findings were compared with neurologic examination findings and presence and severity of SM on MRI. RESULTS: Thirty-three dogs were symptomatic and 17 asymptomatic; 30 had SM. The most common sign of pain was crying out when lifted (n = 11). Extent of shaded areas on maps positively correlated with questionnaire scores for pain (r2  = 0.213, P = 0.006) and scratch (r2  = 0.104, P = 0.089). Owner-reported findings were not significantly associated with presence or severity of SM or neurologic examination findings. Owner-reported lateralization of signs was significantly associated with SM lateralization (P < 0.0001). CONCLUSIONS: The questionnaire and maps may be useful for clinical trials. Lack of association of owner-reported signs with SM highlights our lack of understanding of the pathophysiology of pain in this disease.

Pilot study to determine the feasibility of radiation therapy for dogs with right atrial masses and hemorrhagic pericardial effusion.

OBJECTIVES: To determine the short-term safety and biologic activity of radiation therapy (RT) for presumptive cardiac hemangiosarcoma in pet dogs. ANIMALS: Six dogs with echocardiographic evidence of a right atrial/auricular mass, and hemorrhagic pericardial effusion, were enrolled in a prospective, single-arm clinical trial. METHODS: A single fraction of 12 Gy was delivered using conformal external beam irradiation. Serum cardiac troponin I and plasma concentrations of vascular endothelial growth factor were quantified before, 4 and 24 h after RT. The frequency of required pericardiocenteses (quantified as the number of pericardiocenteses per week) before RT was compared to that after treatment. Overall survival time was determined. RESULTS: No treatment-related complications were observed. Pericardiocentesis was performed an average of 0.91 times per week before RT, and an average of 0.21 times per week after RT; this difference was statistically significant (p=0.03, as compared using a Wilcoxon signed-rank test of paired data). Pre- and post-treatment plasma vascular endothelial growth factor concentrations were not significantly different at any time point; there was a statistically significant (p=0.04; Friedman's test for non-parametric repeated measures) increase in cardiac troponin concentrations 4 h after irradiation. Median overall survival time was 79 days. CONCLUSIONS: In this population of dogs, RT was delivered without complication, and appears to have reduced the frequency of periacardial tamponade that necessitated pericardiocentesis. Serum cardiac troponin levels are altered after RT. RT alone, or in combination with chemotherapy, may provide clinical benefit to dogs with presumptive diagnoses of cardiac hemangiosarcoma.

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

BACKGROUND: In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. METHODS: Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml-1) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. RESULTS: At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. CONCLUSIONS: EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

Effect of Cranberry Extract on the Frequency of Bacteriuria in Dogs with Acute Thoracolumbar Disk Herniation: A Randomized Controlled Clinical Trial.

BACKGROUND: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. HYPOTHESIS: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH. ANIMALS: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status. METHODS: Randomized, placebo-controlled, blinded, prospective clinical trial. Dogs with acute TL-IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi-squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria. RESULTS: Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047). CONCLUSIONS AND CLINICAL IMPORTANCE: This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.

Clinical and Diagnostic Imaging Features of Brain Herniation in Dogs and Cats.

BACKGROUND: Quantification of brain herniation on MRI and its immediate clinical implications are poorly described. OBJECTIVES: Define the normal position of caudal fossa structures on brain MRIs in dogs and cats utilizing morphometry, compare this to dogs and cats with caudal transtentorial herniation (CTH), foramen magnum herniation (FMH) or both identified on MRI, and investigate associations between herniation severity, clinical signs, and 24-hour outcome. ANIMALS: Ninety-two controls (66 dogs, 26 cats), 119 cases with herniation (88 dogs, 31 cats). METHODS: Retrospective case series. The MRI database was searched for controls with normal brain anatomy and cases with brain herniation. Morphometry in controls established TTX (transtentorial to rostroventral cerebellum) to quantify CTH and FMX (caudoventral cerebellum to foramen magnum) to quantify FMH. Measurements were compared between cases and controls. Correlations with specific clinical variables and outcome were investigated. RESULTS: Measurements in medium/large control dogs versus small dog and cat controls were significantly different (P < .001, TTX: -0.46, -0.305, -0.3, FMX: 0.695, 0.27, 0.25, respectively). 119/1564 (7.6%) cases that underwent brain imaging had brain herniation. TTX and FMX were significantly different between controls and cases with CTH or FMH (P < .001). 67/89 (75%) cases with supratentorial lesions had no signs directly attributable to herniation. 71/119 (60%) had a normal anesthetic recovery. TTX was significantly associated with 24-hour survival (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Brain herniation can be quantified on MRI. Clinical signs directly attributable to brain herniation commonly are absent, and more severe CTH based on TTX is associated with a worse short-term outcome.

Longitudinal Study of the Relationship among Craniocervical Morphology, Clinical Progression, and Syringomyelia in a Cohort of Cavalier King Charles Spaniels.

BACKGROUND: Craniocervical junction (CCJ) anomalies and secondary syringomyelia are commonly diagnosed in Cavalier King Charles spaniel (CKCS). Familiarity with the natural history of these abnormalities is vital to understanding the disease syndrome. OBJECTIVE: To evaluate magnetic resonance imaging (MRI) predictors of worsening clinical signs, syringomyelia, and morphology in CKCS longitudinally. ANIMALS: Fifty-four client-owned CKCS, 5-13 years old; 50% currently symptomatic. METHODS: Longitudinal observational study. We enrolled CKCS with an MRI of the CCJ performed ≥3 years earlier. We used questionnaires and neurologic examinations to grade initial and current clinical status. Dogs that could be anesthetized were reimaged. Morphologic assessments included the presence and severity of: Chiari-like malformations, medullary position, atlantooccipital overlapping (AOO), dorsal atlantoaxial bands, and syringomyelia. Cranial cavity volumes and foramen magnum height were measured. RESULTS: Clinical status was evaluated in 54 dogs; 36/54 were reimaged. Mean follow-up was 71 months. Of initially asymptomatic dogs, 32% were symptomatic at re-evaluation. Of initially symptomatic dogs, 56% had worsened; 13% had improved with medical management. The morphology of the CCJ at initial imaging did not predict development of either new or worsened signs or syringomyelia by the time of re-evaluation. CONCLUSION: Craniocervical junction anomalies assessed in this study did not appear predictive of future clinical status or syringomyelia in our cohort. The impacts of syringomyelia, AOO, and atlantoaxial bands on future clinical status merit further study in larger groups of CKCS. Clinical progression in our cohort of medically managed CKCS did not differ substantially from published reports of those treated surgically.

Outcome and survival in canine sick sinus syndrome and sinus node dysfunction: 93 cases (2002-2014).

INTRODUCTION: To evaluate the clinical presentation, diagnosis, treatment, and outcomes of a group of dogs with sinoatrial node abnormalities. ANIMALS: Ninety-three client-owned dogs at a referral institution. MATERIALS AND METHODS: Medical records were reviewed for clinical history, diagnostic testing, and medical or permanent artificial pacemaker (PAP) treatment. Owners or veterinarians were contacted for long-term follow-up. RESULTS: Sixty-one dogs were symptomatic for their bradyarrhythmia and were diagnosed with sick sinus syndrome (SSS). Thirty-two dogs were asymptomatic for their bradyarrhythmia and were diagnosed with sinus node dysfunction (SND). Miniature Schnauzers, West Highland White terriers, Cocker spaniels, and female dogs were overrepresented. Medical management with positive chronotropic drugs successfully controlled syncope long-term in 54% of SSS dogs, and acted as a bridge to PAP in 20%. Positive atropine response predicted medical treatment success. Forty-six percent of SSS dogs eventually underwent PAP implantation. Median survival time was approximately 18 months in SND and SSS dogs regardless of treatment strategy. Congestive heart failure (CHF) associated with progressive valvular heart disease occurred commonly in all groups, particularly in dogs with bradycardia-tachycardia syndrome. CONCLUSIONS: Sinus node dysfunction and SSS represent a spectrum of sinoatrial node disease, which for some dogs may also involve a component of autonomic dysfunction. Dogs with SND do not require treatment. Dogs with SSS often require treatment to reduce the frequency of syncope; medical management is often useful, particularly in atropine responsive dogs. Prognosis of SSS with treatment is good, though development of CHF does not appear to be mitigated by treatment.

Recovery of stepping and coordination in dogs following acute thoracolumbar intervertebral disc herniations.

Prospective data on the recovery of coordination in dogs suffering acute thoracolumbar intervertebral disc herniations (TL-IVDH) are limited. The purpose of this study was to use treadmill based and open field scores (OFS) to quantify recovery of stepping ability and forelimb, hindlimb coordination in the 6 weeks following surgical decompression of dogs with TL-IVDH. Sixty-three dogs were grouped at presentation as grades 3 (non-ambulatory paraparetic), 4 (paraplegic) or 5 (paraplegic without pain sensation) and were evaluated 2, 4, and 6 weeks post-operatively. Stepping scores and Regularity Index (RI), a measure of coordination, were calculated from treadmill walking, and an OFS incorporating supported and unsupported walking was assigned. Outcomes for the three measures were compared between groups and correlation between scoring methods was assessed. Grade 3 and 4 dogs recovered ambulation by 2 weeks, reaching median stepping scores of 96 and 90% by 6 weeks, respectively. Recovery of coordination differed between groups 3 and 4 with median RI scores of 93.9% and 63%, respectively, by 6 weeks. Eight grade 5 dogs failed to recover independent ambulation by 6 weeks. Nine dogs recovered with scores that were significantly worse than the grade 3 and 4 dogs at 6 weeks for stepping score (P < 0.001) and RI (P < 0.001). OFS correlated closely with stepping and RI scores and each group was significantly different using this ordinal scale. In conclusion, recovery of coordination was incomplete in dogs that showed good recovery of stepping. The data generated could be used for clinical trial design.

A Feline-Specific Anti-Nerve Growth Factor Antibody Improves Mobility in Cats with Degenerative Joint Disease-Associated Pain: A Pilot Proof of Concept Study.

BACKGROUND: Neutralizing antibodies against nerve growth factor (NGF) are analgesic in rodent models, naturally occurring degenerative joint disease (DJD) pain in dogs, and chronic pain in humans. OBJECTIVES: To evaluate the efficacy of a fully felinized anti-NGF antibody (NV-02) for the treatment of DJD pain and mobility impairment in cats. ANIMALS: Thirty-four client-owned cats with DJD-associated pain and mobility impairment. METHODS: In a placebo-controlled, pilot, masked clinical study, cats were randomized to a single treatment with NV-02 (0.4 mg/kg SC [n = 11] or 0.8 mg/kg SC [n = 12]) or placebo (saline, SC [n = 11]). Activity was measured objectively. Additionally, owners completed clinical metrology instruments (client-specific outcome measures [CSOM] and feline musculoskeletal pain index [FMPI]) on days 0 (screening), 14 (baseline), 35, 56, and 77. A repeated-measures model was used to evaluate the objective activity data. RESULTS: NV-02 significantly increased objectively measured activity overall (P = .017) and at 2 (P = .035), 3 (P = .007), 4 (P = .006), 5 (P = .007), and 6 (P = .017) weeks after treatment. CSOM scores (P = .035) and pain (P = .024) showed a significant effect of treatment 3 weeks after administration. In the treatment group, 83% of the owners correctly identified the treatment administered compared with 45% of owners in the placebo group (P = .013). No treatment-related adverse effects were identified. CONCLUSIONS: These pilot data demonstrate a 6-week duration positive analgesic effect of this fully felinized anti-NGF antibody in cats suffering from DJD-associated pain.

Association of Canine Osteosarcoma and Monocyte Phenotype and Chemotactic Function.

BACKGROUND: Monocytes/macrophages are likely key cells in immune modulation in dogs with osteosarcoma (OSA). Increased peripheral monocyte counts are negatively correlated with shorter disease-free intervals in dogs with OSA. Understanding the monocyte/macrophage's modulatory role in dogs with OSA can direct further studies in immunotherapy development for OSA. HYPOTHESIS/OBJECTIVES: That OSA evades the immune response by down-regulating monocyte chemokine receptor expression and migratory function, and suppresses host immune responses. ANIMALS: Eighteen dogs with OSA that have not received definitive treatment and 14 healthy age-matched controls METHODS: Clinical study-expression of peripheral blood monocyte cell surface receptors, monocyte mRNA expression and cytokine secretion, monocyte chemotaxis, and survival were compared between clinical dogs with OSA and healthy control dogs. RESULTS: Cell surface expression of multiple chemokine receptors is significantly down-regulated in peripheral blood monocytes of dogs with OSA. The percentage expression of CCR2 (median 58%, range 2-94%) and CXCR2 expression (median 54%, range 2-92%) was higher in control dogs compared to dogs with OSA (CCR2 median 29%, range 3-45%, P = 0.0006; CXCR2 median 23%, range 0.2-52%, P = 0.0007). Prostaglandin E2 (PGE2 ) (OSA, median 347.36 pg/mL, range 103.4-1268.5; control, 136.23 pg/mL, range 69.93-542.6, P = .04) and tumor necrosis factor-alpha (TNF-α) (P = .02) levels are increased in OSA monocyte culture supernatants compared to controls. Peripheral blood monocytes of dogs with OSA exhibit decreased chemotactic function when compared to control dogs (OSA, median 1.2 directed to random migration, range 0.8-1.25; control, 1.6, range of 0.9-1.8, P = .018). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with OSA have decreased monocyte chemokine receptor expression and monocyte chemotaxis, potential mechanisms by which OSA might evade the immune response. Reversal of monocyte dysfunction using immunotherapy could improve survival in dogs with OSA.

Mechanical and Thermal Sensory Testing in Normal Chondrodystrophoid Dogs and Dogs with Spinal Cord Injury caused by Thoracolumbar Intervertebral Disc Herniations.

BACKGROUND: Intervertebral disc herniation is a common cause of spinal cord injury (SCI) causing paralysis and sensory loss. Little quantitative information is available on the loss and recovery of sensation in dogs with SCI. OBJECTIVES: To determine whether quantitative sensory testing (QST) can be used to establish thermal and mechanical sensory thresholds in chrondrodystrophoid dogs and compare thresholds among normal dogs and dogs with different grades of SCI. ANIMALS: Thirty-three client-owned chondrodystrophoid dogs: 15 normal and 18 SCI dogs. METHODS: Thermal testing was performed by placing a hot (49°C) and cold (5°C) probe on the dorsal metatarsus and mechanical thresholds were tested using calibrated forceps to apply force to the lateral digit. Stimuli were applied until acknowledged, and response rate, latency, and force applied to response were recorded. Test-retest repeatability was determined by calculating intraclass correlation coefficients. Response rates were compared using logistic regression and thresholds were compared using Kaplan-Meier Survival curves. RESULTS: Testing was feasible with moderate repeatability. Thresholds and response rates were significantly different between normal and SCI dogs for all modalities (P < .001). When dogs were grouped by their clinical grade, each grade was significantly different from normal dogs, and cold stimuli differentiated among all grades. CONCLUSION AND CLINICAL IMPORTANCE: Sensory thresholds can be measured reliably in chondrodystrophoid dogs and are altered by SCI. The differences in sensation among neurologic grades indicate that these techniques can be used to further characterize recovery of SCI dogs.

Pilot randomised trial of a brief intervention for comorbid substance misuse in psychiatric in-patient settings.

OBJECTIVE: This proof of principle study evaluated the effectiveness and feasibility of a brief motivational intervention, delivered in mental health in-patient settings, to improve engagement in treatment for drug and alcohol misuse. METHOD: A randomised controlled trial using concealed randomisation, blind, independent assessment of outcome at 3 months. Participants were 59 new adult admissions, to six acute mental health hospital units in one UK mental health service, with schizophrenia related or bipolar disorder diagnoses, users of community mental health services and also misusing alcohol and/or drugs. Participants were randomised to Brief Integrated Motivational Intervention (BIMI) with Treatment As Usual (TAU), or TAU alone. The BIMI took place over a 2-week period and encouraged participants to explore substance use and its impact on mental health. RESULTS: Fifty-nine in-patients (BIMI n = 30; TAU n = 29) were randomised, the BIMI was associated with a 63% relative odds increase in the primary outcome engagement in treatment [OR 1.63 (95% CI 1.01-2.65; P = 0.047)], at 3 months. Qualitative interviews with staff and participants indicated that the BIMI was both feasible and acceptable. CONCLUSION: Mental health hospital admissions present an opportunity for brief motivational interventions focussed on substance misuse and can lead to improvements in engagement.

Dorsal compressive atlantoaxial bands and the craniocervical junction syndrome: association with clinical signs and syringomyelia in mature cavalier King Charles spaniels.

BACKGROUND: Dorsal compressive lesions at the atlantoaxial junction (ie, AA bands) occur in dogs with Chiari-like malformations (CMs), but their clinical relevance is unclear. OBJECTIVE: Investigate the influence of AA bands on clinical status and syringomyelia (SM) in mature cavalier King Charles spaniels (CKCS). ANIMALS: Thirty-six CKCS, 5-12 years of age, including 20 dogs with neuropathic pain. METHODS: Dogs were examined and assigned a neurologic grade. Magnetic resonance imaging (MRI) of the craniocervical junction was performed with the craniocervical junction extended and flexed (ie, normal standing position). Imaging studies were assessed for the presence of an AA band, CM, SM or some combination of these findings. Band and SM severity were quantified using an objective compression index and ordinal grading scale, respectively. RESULTS: Of 36 CKCS imaged, 34 had CM. Atlantoaxial bands were associated with the presence (P = .0031) but not the severity (P = .008) of clinical signs, whereas their presence was associated with both the presence and severity of SM (P = .0147, P = .0311, respectively ). Higher compression indices were associated with more severe SM (P = .0137). CONCLUSIONS: Prevalence of AA bands in older CKCS is high. Positioning of dogs in extension during MRI enhances the sensitivity of the study for detecting this important abnormality. There were significant associations among AA bands, clinical signs, and SM in dogs with CM; additional work is needed to understand whether or not this relationship is causal.

Medullary position at the craniocervical junction in mature cavalier King Charles spaniels: relationship with neurologic signs and syringomyelia.

BACKGROUND: Medullary elevation (ie, medullary kinking) at the craniocervical junction (CCJ) is reported in dogs with Chiari-like malformations (CM), but its diagnostic criteria and clinical relevance are unclear. OBJECTIVE: To describe the position of the medulla at the CCJ in mature cavalier King Charles spaniels (CKCS), and evaluate its relationship with clinical status and the presence of syringomyelia. ANIMALS: Thirty-six CKCS, 5-12 years of age, including 16 asymptomatic dogs. METHODS: Dogs were assigned a neurologic grade; magnetic resonance imaging (MRI) of the CCJ then was performed. The presence of a CM and syringomyelia was recorded and syringomyelia severity was quantified. Medullary position was quantified using the medullary kinking index, the elevation angle and obex position relative to the foramen magnum. The relationship between medullary position measures and presence and severity of neurologic signs and syringomyelia was investigated. RESULTS: Chiari-like malformation was found in 33 dogs; 26 of them had syringomyelia. Mean medullary kinking index was 46.4% (SD, 10.3), elevation angle was 132° (SD, 12) and obex position was 3.5 mm (SD, 0.8). A higher medullary kinking index was associated with the presence of neurologic signs (P = .0368). Obex position was associated with the presence (P = .0018) and severity of syringomyelia (P = .0164). CONCLUSIONS AND CLINICAL IMPORTANCE: There is a significant association between medullary elevation and clinical signs, whereas more caudal brainstem positions appear related to the presence of syringomyelia.

Complication rates associated with transvenous pacemaker implantation in dogs with high-grade atrioventricular block performed during versus after normal business hours.

BACKGROUND: Transvenous pacemaker implantation in dogs is associated with a relatively high complication rate. At our institution, pacemaker implantation in dogs with high-grade atrioventricular block (HG-AVB) frequently is performed as an after-hours emergency. HYPOTHESIS: Among dogs with HG-AVB, the rate of major complications is higher when pacemakers are implanted after hours (AH) compared to during business hours (BH). ANIMALS: Client-owned dogs with HG-AVB that underwent transvenous pacemaker implantation between January 2002 and December 2012 at the North Carolina State University Veterinary Teaching Hospital. METHODS: Retrospective medical record review. Two-year follow-up was required for complications analysis. RESULTS: Major complications occurred in 14/79 dogs (18%) and included lead dislodgement, lead or generator infection, lead or generator migration, and pacing failure. Incidence of major complications was significantly higher AH (10/36, 28%) compared to BH (4/43, 9%; P = .041), and all infectious complications occurred AH. Median survival time for all dogs was 27 months and did not differ between AH and BH groups for either all-cause (P = .70) or cardiac (P = .40) mortality. AH dogs were younger than BH dogs (P = .010), but there were no other clinically relevant differences between BH and AH groups in terms of demographic, clinical, or procedural variables. CONCLUSIONS AND CLINICAL IMPORTANCE: At our institution, AH transvenous pacemaker placement is associated with a higher rate of major complications (especially infections) compared to BH placement. This difference may be because of a variety of human factor differences AH versus BH.

Detection of clinically relevant pain relief in cats with degenerative joint disease associated pain.

BACKGROUND: Detection of clinically relevant pain relief in cats with degenerative joint disease (DJD) is complicated by a lack of validated outcome measures and a placebo effect. HYPOTHESIS/OBJECTIVES: To evaluate a novel approach for detection of pain relief in cats with DJD. ANIMALS: Fifty-eight client-owned cats. METHODS: Prospective, double-masked, placebo-controlled, stratified, randomized, clinical study. Enrolled cats were 6-21 years of age, with owner-observed mobility impairment, evidence of pain in at least 2 joints during orthopedic examination, and overlapping radiographic evidence of DJD, and underwent a 2-week baseline period, 3-week treatment period with placebo or meloxicam, and 3-week masked washout period. Outcome measures were evaluated at days 0, 15, 36, and 57. RESULTS: Both groups significantly improved after the treatment period (day 36) on client-specific outcome measures (CSOM) and feline musculoskeletal pain index (FMPI) (P < .0001 for both); there was no difference between the groups on CSOM or FMPI score improvement. After the masked washout period, more cats that received meloxicam during the treatment period had a clinically relevant decrease in CSOM score (P = .048) and FMPI score (P = .021) than cats that received placebo. CONCLUSIONS AND CLINICAL IMPORTANCE: Using both a client-specific and a general clinical metrology instrument, owners of cats with DJD were able to detect evident recurrence of clinical signs after withdrawal of active medication than after withdrawal of placebo, and that this study design might be a novel and useful way to circumvent the placebo effect and detect the efficacy of pain-relieving medications.

Safety and effectiveness of a glistening-free single-piece hydrophobic acrylic intraocular lens (enVista).

PURPOSE: To evaluate the safety and effectiveness of a single-piece hydrophobic acrylic intraocular lens (IOL; enVista model MX60; Bausch & Lomb, Rochester, NY, USA) when used to correct aphakia following cataract extraction in adults. METHODS: This was a prospective case series (NCT01230060) conducted in private practices in the US. Eligible subjects were adult patients with age-related cataract amenable to treatment with standard phacoemulsification/extracapsular cataract extraction. With follow-up of 6 months, primary safety and effectiveness end points included the rates of US Food and Drug Administration (FDA)-defined cumulative and persistent adverse events and the percentage of subjects who achieved best-corrected visual acuity (BCVA) of 20/40 or better at final visit. To evaluate rotational stability, subjects were randomized (1:1:1:1) to have the lens implanted in one of four axis positions in 45° increments. RESULTS: A total of 122 subjects were enrolled. The rate of cumulative and persistent adverse events did not significantly exceed historical controls, as per FDA draft guidance. At the final postoperative visit, all subjects (100%) achieved a BCVA of 20/40 compared with the FDA historical control of 96.7%. Rotation of the IOL between the two final follow-up visits was ≤5° for 100% of eyes, and refractive stability was demonstrated. A low evaluation of posterior capsule opacification score was demonstrated, and no glistenings of any grade were reported for any subject at any visit. CONCLUSION: This study demonstrated the safety and effectiveness of the MX60 IOL. Favorable clinical outcomes included preserved BCVA, excellent rotational and refractive stability, no glistenings, and a low evaluation of posterior capsule opacification score.

Antihypertensive medications and survival in patients with cancer: a population-based retrospective cohort study.

BACKGROUND: The association between antihypertensive medications and survival in cancer patients remains unclear. OBJECTIVES: To explore the association between classes of antihypertensive drugs and survival in cancer patients. METHODS: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n=4241), colorectal (n=3967), breast (n=4019) or prostate (n=3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. RESULTS: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04-1.44) and lung cancer (HR: 1.11, 95% CI: 1.03-1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02-1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01-1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15-1.42), and prostate (HR 1.41, 1.2-1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64-0.98). CONCLUSIONS: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.