Thoracolumbar hydrated nucleus pulposus extrusion and intervertebral disc extrusion in dogs: Comparison of clinical presentation and magnetic resonance imaging findings.

Thoracolumbar hydrated nucleus pulposus extrusion (TL-HNPE) is an increasingly recognised pathology with a substantial lack of literature describing its features. The aim of this retrospective case-control study was to analyse the clinical and magnetic resonance imaging (MRI) features of dogs with TL-HNPE compared to dogs affected with thoracolumbar intervertebral disc extrusion (TL-IVDE). Data from dogs diagnosed with TL-HNPE and TL-IVDE via MRI at two referral hospitals, were retrospectively collected and compared in terms of clinical signs and MRI features. Cases diagnosed with TL-IVDE were deemed controls. The MRI features of the affected IVD space, herniated IVD material, affected overlying spinal cord and local epaxial musculature were evaluated for each group. Fifty-one cases with TL-HNPE and 105 randomly selected cases of TL-IVDE were included. Several signalment and neurological signs were identified as statistically distinct between groups in univariate analysis. Multivariate analysis identified that dogs affected with TL-HNPE were typically older, less likely to be chondrodystrophic (62.2 % vs. 91 %), more frequently experiencing a peracute onset (90.2 % vs. 61.9 %) often attributed to a suspected trauma linked with exercise (37.3 % vs. 10.5 %), being less frequently progressive (41.2 % vs. 86.5 %) and with herniated disc material less frequently lateralised (72.6 % vs. 89.5 %) than cases with TL-IVDE. MRI-identifiable intervertebral disc degeneration was found in every TL-IVDE case but only in 60 % of TL-HNPE cases. TL-HNPEs were associated to significantly less spinal cord compression and less hyperalgesia than TL-IVDE.

Frequency and risk factors for naturally occurring Cushing's syndrome in dogs attending UK primary-care practices.

OBJECTIVES: To estimate the frequency and risk factors for Cushing's syndrome in dogs under UK primary veterinary care. MATERIALS AND METHODS: Dogs with Cushing's syndrome were identified by searching electronic patient records of primary-care veterinary practices. Pre-existing and incident cases of Cushing's syndrome during 2016 were included to estimate the 1-year period prevalence. Incident cases were used to estimate the annual incidence and to identify demographic risk factors for the diagnosis of Cushing's syndrome in dogs, through multivariable logistic regression. RESULTS: Analysis included 970 pre-existing and 557 incident cases of Cushing's syndrome from a population of 905,544 dogs. The estimated 1-year period prevalence for Cushing's syndrome in dogs under veterinary care was 0.17% (95% confidence interval 0.16 to 0.18) and incidence was 0.06% (95% confidence interval 0.05 to 0.07). In multivariable logistic regression modelling, the Bichon frise (odds ratio=6.17, 95% confidence interval 4.22 to 9.00), Border terrier (5.40, 95% confidence interval 3.66 to 7.97) and Miniature schnauzer (3.05, 95% confidence interval 1.67 to 5.57) had the highest odds of Cushing's syndrome. The Golden retriever (0.24, 95% confidence interval 0.06 to 0.98) and Labrador retriever (0.30, 95% confidence interval 0.17 to 0.54) were the most protected breeds. Increasing age, bodyweight greater than the breed-sex mean and being insured also showed increased odds of Cushing's syndrome. CLINICAL SIGNIFICANCE: As Cushing's syndrome is predominately diagnosed and managed in primary-care practice, this study provides valuable new information of its epidemiology in this setting. Demographics reported are supportive of previous work and additional novel associations identified, such as the Border terrier, could enhance the index of suspicion for veterinarians.

Hypoadrenocorticism in dogs under UK primary veterinary care: frequency, clinical approaches and risk factors.

OBJECTIVES: To estimate the frequency, clinical approaches and risk factors of hypoadrenocorticism in dogs under UK primary veterinary care. MATERIALS AND METHODS: Dogs diagnosed with hypoadrenocorticism were identified from the UK VetCompass™ programme by searching anonymised electronic patient records. Pre-existing and newly diagnosed cases of disease during 2016 were included. Cases were further sub-categorised as having a laboratory-confirmed or presumed diagnosis of hypoadrenocorticism based on the information recorded in the electronic patient records. Descriptive data were manually extracted. Multivariable logistic regression methods were used to identify demographic risk factors. RESULTS: There were 177 hypoadrenocorticism cases identified from 905,543 dogs in 2016; 72 laboratory-confirmed and 105 presumed. The 1-year period prevalence for hypoadrenocorticism in all dogs was 0.06% (95% confidence interval: 0.05-0.07%). The most common presenting clinical signs in laboratory-confirmed dogs were lethargy (51/66, 77.3%), anorexia (48/66, 66.7%) and vomiting (48/66, 66.7%). Hyperkalaemia was reported in 47 of 53 (88.7%), hyponatraemia in 46 of 53 (86.8%). Median sodium: potassium ratio was 19.00 (interquartile range: 16.20-20.60). Breed, age, neuter status and insurance status were associated with a laboratory-confirmed diagnosis of hypoadrenocorticism. No sex association with hypoadrenocorticism was observed in the multivariable model. The standard poodle had 51.38 times the odds (95% CI: 14.49-182.18) of hypoadrenocorticism compared with crossbreeds. The labradoodle and West Highland white terrier also had increased odds. CLINICAL SIGNIFICANCE: This is the first epidemiological study to report on hypoadrenocorticism in dogs within the UK primary-care population. These results provide benchmark data of current veterinary activity relating to hypoadrenocorticism in primary-care practices.

Incidence and risk factors for feline lymphoma in UK primary-care practice.

OBJECTIVES: The study aimed to estimate the incidence and prevalence of feline lymphoma in cats attending primary-care practices across the UK and to identify patient-based and environmental (radon and pesticide exposure) risk factors. MATERIALS AND METHODS: Case records from the VetCompass programme from primary-care veterinary practices in the UK were searched for a diagnosis of lymphoma in cats in 2016. Cases were required to have had an external laboratory confirmed diagnosis based on cytology and/or histopathology. A nested case-control study design was used to identify risk factors for lymphoma using multivariable logistic regression. RESULTS: From a cohort of 562,446 cats under veterinary care at VetCompass participating practices in 2016, a total of 271 lymphoma cases were identified (prevalence: 48/100,000, 95% confidence interval (CI) 44 to 56/100,000; incidence 32/100,000, 95% CI 26 to 35/100,000). There were 180 incident lymphoma cases and 803 controls, all aged 2 years and older. Male (odds ratio (OR) 1.7, 95% CI 1.2 to 2.4), insured (OR 3.6, 95% CI 2.3 to 5.6) and older cats (compared to cats 2 to <5 years, OR 5.0, 95% CI 2.8 to 8.8) were associated with increased odds of lymphoma diagnosis. Vaccinated cats were associated with decreased odds (OR 0.7, 95% CI 0.5 to 1.0) compared to unvaccinated cats, although the type of vaccination received was not statistically significant. Breed and environmental factors studied were not associated with a diagnosis of lymphoma. CLINICAL SIGNIFICANCE: This is the first study to estimate the frequency and report risk factors for lymphoma in cats attending UK primary-care practice.

Geographic distribution and environmental risk factors of lymphoma in dogs under primary-care in the UK.

OBJECTIVES: To integrate external data sources with VetCompass postcode data to explore the spatial distribution and examine potential associations with environmental risk factors in dogs diagnosed with lymphoma at primary care veterinary practices. MATERIALS AND METHODS: Cases of lymphoma were identified from electronic patient records of 455,553 dogs under primary veterinary care during 2013 in the UK. Cases were defined as either laboratory-confirmed or non-laboratory-confirmed. Disease maps at the postcode-district level were used to define the geographic distribution of lymphoma incidence and spatial clustering was explored. Environmental risk factors from external data sources were transferred to a compatible format and logistic regression modelling was used to examine associations between environmental herbicide, fungicide and radon concentrations with lymphoma. RESULTS: From the denominator population of 455,553 dogs, 279 lymphoma cases (187 with laboratory confirmation and 93 without) were identified. Heterogeneous geographic variation was observed with weak evidence of clustering around London and the south-west of England. Herbicide and fungicide exposures were weakly associated with a diagnosis of lymphoma in the univariable analysis. After accounting for the age at diagnosis and breed in the multivariable analysis, herbicide exposure was associated with a diagnosis of lymphoma. CLINICAL SIGNIFICANCE: The heterogeneous distribution of lymphoma in UK dogs provides further evidence for geographic variation of lymphoma, perhaps in part associated with underlying environmental risk factors. The results suggest an association between environmental herbicide and canine lymphoma.

Incidence and risk factors for the diagnosis of lymphoma in dogs in UK primary-care practice.

OBJECTIVES: To identify the incidence, risk factors and presenting signs of lymphoma in dogs presenting to primary-care practice in the UK using analysis of data within the VetCompass™ programme. MATERIALS AND METHODS: Case records from the VetCompass™ programme from primary-care practices in the UK were searched for newly diagnosed lymphoma in dogs within a 1-year period: 2013. Diagnosis was based on clinical records with or without laboratory confirmation. Signalment was evaluated as risk factors for lymphoma diagnosis using multivariable logistic regression. RESULTS: There were 286 presumed newly diagnosed cases identified during 2013 from 455,553 dogs (overall incidence risk 63 of 100,000 dogs per year) of which 193 (67%) were laboratory confirmed (42 of 100,000 dogs per year). Advanced age, dogs older than 12 years, dogs weighing more than 30 kg and some specific breeds were significantly associated with lymphoma diagnosis. Only 18 dogs (6%) of the population identified were referred to a specialist clinic. CLINICAL SIGNIFICANCE: This study concurs with others that age, bodyweight and breed are significant risk factors for lymphoma. Results of this study highlight: (1) the low number of dogs with lymphoma that are referred to specialists in the UK and (2) that few dogs undergo immunophenotyping (which can carry prognostic importance), emphasising the importance of epidemiological programmes that evaluate diseases presented to primary-care veterinarians.

Diagnostic criteria for amyotrophic lateral sclerosis: A multicentre study of inter-rater variation and sensitivity.

OBJECTIVE: This study assesses inter-rater agreement and sensitivity of diagnostic criteria for amyotrophic lateral sclerosis (ALS). METHODS: Clinical and electrophysiological data of 399 patients with suspected ALS were collected by eleven experienced physicians from ten different countries. Eight physicians classified patients independently and blinded according to the revised El Escorial Criteria (rEEC) and to the Awaji Criteria (AC). Inter-rater agreement was assessed by Kappa coefficients, sensitivity by majority diagnosis on 350 patients with follow-up data. RESULTS: Inter-rater agreement was generally low both for rEEC and AC. Agreement was best on the categories "Not-ALS", "Definite", and "Probable", and poorest for "Possible" and "Probable Laboratory-supported". Sensitivity was equal for rEEC (64%) and AC (63%), probably due to downgrading of "Probable Laboratory-supported" patients by AC. However, AC was significantly more effective in classifying patients as "ALS" versus "Not-ALS" (p < 0.0001). CONCLUSIONS: Inter-rater variation is high both for rEEC and for AC probably due to a high complexity of the rEEC inherent in the AC. The gain of AC on diagnostic sensitivity is reduced by the omission of the "Probable Laboratory-supported" category. SIGNIFICANCE: The results highlight a need for initiatives to develop simpler and more reproducible diagnostic criteria for ALS in clinical practice and research.

Added value of electromyography in the diagnosis of myopathy: A consensus exercise.

OBJECTIVE: Currently, neurologists may primarily rely on blood biomarkers, muscle biopsy, MRI, and genetics in the diagnostic work-up of suspected myopathy. Using expert consensus as diagnostic reference standard, this study addressed the added value of electrodiagnostic medicine (EDX) in diagnosis of myopathies. METHODS: One hundred ninety-four EDX evaluations of patients with a peer-review consensus diagnosis of myopathy were collected by seven European centres. Each patient was given three different consensus diagnoses: (1) the EDX diagnosis solely based on EDX results, (2) the pure clinical diagnosis based on all available information except EDX results, and (3) the final diagnosis including EDX and all additional information. The myopathies were grouped as muscular dystrophy (45), inflammatory myopathy (46), other aetiology (36) or unknown aetiology (67). RESULTS: Higher diagnostic probabilities for myopathy were seen in the final diagnosis compared to the pure clinical diagnosis (p<0.001). Adding EDX information increased the diagnostic probability of myopathy in 67 patients (34.4%). The greatest increase was seen for myopathies of unknown aetiology. CONCLUSIONS: EDX has a major impact in the diagnosis of myopathies of unknown aetiology. In genetically or biopsy proven myopathies, EDX generally supports the diagnosis. SIGNIFICANCE: EDX is still a useful tool in the diagnostic work-up of most patients with suspected myopathy.

Unbalanced Peptidergic Inhibition in Superficial Neocortex Underlies Spike and Wave Seizure Activity.

Slow spike and wave discharges (0.5-4 Hz) are a feature of many epilepsies. They are linked to pathology of the thalamocortical axis and a thalamic mechanism has been elegantly described. Here we present evidence for a separate generator in local circuits of associational areas of neocortex manifest from a background, sleep-associated delta rhythm in rat. Loss of tonic neuromodulatory excitation, mediated by nicotinic acetylcholine or serotonin (5HT3A) receptors, of 5HT3-immunopositive interneurons caused an increase in amplitude and slowing of the delta rhythm until each period became the "wave" component of the spike and wave discharge. As with the normal delta rhythm, the wave of a spike and wave discharge originated in cortical layer 5. In contrast, the "spike" component of the spike and wave discharge originated from a relative failure of fast inhibition in layers 2/3-switching pyramidal cell action potential outputs from single, sparse spiking during delta rhythms to brief, intense burst spiking, phase-locked to the field spike. The mechanisms underlying this loss of superficial layer fast inhibition, and a concomitant increase in slow inhibition, appeared to be precipitated by a loss of neuropeptide Y (NPY)-mediated local circuit inhibition and a subsequent increase in vasoactive intestinal peptide (VIP)-mediated disinhibition. Blockade of NPY Y1 receptors was sufficient to generate spike and wave discharges, whereas blockade of VIP receptors almost completely abolished this form of epileptiform activity. These data suggest that aberrant, activity-dependent neuropeptide corelease can have catastrophic effects on neocortical dynamics.

Generalised sensory system abnormalities in amyotrophic lateral sclerosis: a European multicentre study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is defined as a disease of the motor neurones, although several studies indicate involvement of the sensory nervous system. AIM: To evaluate the sensory nerve conduction studies (NCS) in 88 patients with ALS as part of a European multicentre study. METHODS: Seven European clinical neurophysiologists examined consecutive series of ALS patients. The examinations were peer reviewed, and the diagnosis of ALS was confirmed clinically. RESULTS: 20 (22.7%) patients with ALS had sensory NCS abnormalities in at least one nerve. Of those, 11 (12.5% of all patients) obtained an additional peer review diagnosis of electrophysiological polyneuropathy. There was no difference between the subgroups of patients with normal versus abnormal sensory NCS findings with respect to age, duration and region of onset. CONCLUSION: The findings support previous reports of sensory involvement in ALS, and raise the question of whether patients with ALS with sensory nerve abnormalities represent a variant of ALS. ALS associated with generalised sensory system abnormalities may be consistent with degeneration of motor neurones and dorsal root ganglion cells.

Amplitude, area and duration of the compound muscle action potential change in different ways over the length of the ulnar nerve.

OBJECTIVE: To study physiological changes of the compound muscle action potential (CMAP) obtained from stimulation at different sites over the full length of a motor nerve and to study possible effects of anthropometrical factors. METHODS: Multicentre study of ulnar motor nerve conduction in five segments to Erb's point performed bilaterally on 100 healthy subjects aged 17-83 years. RESULTS: CMAP amplitude decreased linearly with conduction distance (0.31%/cm) from wrist to Erb's point. CMAP area decreased with the square of conduction distance. Decrease in area was smaller than decrease in amplitude especially distally. CMAP duration increased linearly (0.17%/cm). Amplitude decay correlated with age, height and BMI and dispersion correlated with age and height. There were no correlations between area decay and anthropometrical factors. There was no significant inter-examiner variation. CONCLUSIONS: Area decay may be preferred to amplitude decay in the evaluation of conduction block over short segments due to smaller physiological changes and independence of anthropometrical factors. The absence of inter-examiner variation indicates that the results are robust and may be used by other laboratories. SIGNIFICANCE: This study provides knowledge of physiological changes of CMAP parameters that may be of importance in the evaluation of nerve pathology, in particular conduction block.

Multivariate prediction of major adverse cardiac events after 9914 percutaneous coronary interventions in the north west of England.

OBJECTIVE: To develop a multivariate prediction model for major adverse cardiac events (MACE) after percutaneous coronary interventions (PCIs) by using the North West Quality Improvement Programme in Cardiac Interventions (NWQIP) PCI Registry. SETTING: All NHS centres undertaking adult PCIs in north west England. METHODS: Retrospective analysis of prospectively collected data on 9914 consecutive patients undergoing adult PCI between 1 August 2001 and 31 December 2003. A multivariate logistic regression analysis was undertaken, with the forward stepwise technique, to identify independent risk factors for MACE. The area under the receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow goodness of fit statistic were calculated to assess the performance and calibration of the model, respectively. The statistical model was internally validated by using the technique of bootstrap resampling. MAIN OUTCOME MEASURES: MACE, which were in-hospital mortality, Q wave myocardial infarction, emergency coronary artery bypass graft surgery, and cerebrovascular accidents. RESULTS: Independent variables identified with an increased risk of developing MACE were advanced age, female sex, cerebrovascular disease, cardiogenic shock, priority, and treatment of the left main stem or graft lesions during PCI. The ROC curve for the predicted probability of MACE was 0.76, indicating a good discrimination power. The prediction equation was well calibrated, predicting well at all levels of risk. Bootstrapping showed that estimates were stable. CONCLUSIONS: A contemporaneous multivariate prediction model for MACE after PCI was developed. The NWQIP tool allows calculation of the risk of MACE permitting meaningful risk adjusted comparisons of performance between hospitals and operators.

Variation in the classification of polyneuropathies among European physicians.

OBJECTIVE: Considerable debate still exists regarding the classification of polyneuropathies (PNPs) into predominantly demyelinating, predominantly axonal loss, mixed or unclassified. This study was designed to determine the variation among physicians in the classification of PNPs by using the European Standardized Telematic tool to Evaluate Electromyography knowledge-based systems and Methods (ESTEEM) multicenter database. METHODS: Seven physicians from 6 laboratories in Europe sent a total of 156 prospectively collected cases of PNP with electromyography (EMG) data including diagnosis (examination diagnosis) to the database. Each physician interpreted the electrophysiological data from all cases (interpretation diagnosis) and a final diagnosis was given at the consensus meetings of the group (consensus diagnosis). RESULTS: Comparison of each physician's examination diagnosis with his/her interpretation diagnosis, i.e. intra-physician variation, showed a change towards less classified PNPs (P < 0.05). Interpretation diagnoses showed large inter-physician variation in the classification of PNPs. The consensus group was more cautious than individual physicians in classifying PNPs as mixed and axonal. The probability of the consensus diagnosis increased with increasing number of abnormal motor and sensory segments tested. CONCLUSIONS: Recognition of variation in classification of PNP as shown in this study and suggesting standards of good clinical practice developed by a consensus group may increase the quality of EMG practice.

An open-label phase II study of low-dose thalidomide in androgen-independent prostate cancer.

The antiangiogenic effects of thalidomide have been assessed in clinical trials in patients with various solid and haematological malignancies. Thalidomide blocks the activity of angiogenic agents including bFGF, VEGF and IL-6. We undertook an open-label study using thalidomide 100 mg once daily for up to 6 months in 20 men with androgen-independent prostate cancer. The mean time of study was 109 days (median 107, range 4-184 days). Patients underwent regular measurement of prostate-specific antigen (PSA), urea and electrolytes, serum bFGF and VEGF. Three men (15%) showed a decline in serum PSA of at least 50%, sustained throughout treatment. Of 16 men treated for at least 2 months, six (37.5%) showed a fall in absolute PSA by a median of 48%. Increasing levels of serum bFGF and VEGF were associated with progressive disease; five of six men who demonstrated a fall in PSA also showed a decline in bFGF and VEGF levels, and three of four men with a rising PSA showed an increase in both growth factors. Adverse effects included constipation, morning drowsiness, dizziness and rash, and resulted in withdrawal from the study by three men. Evidence of peripheral sensory neuropathy was found in nine of 13 men before treatment. In the seven men who completed six months on thalidomide, subclinical evidence of peripheral neuropathy was found in four before treatment, but in all seven at repeat testing. The findings indicate that thalidomide may be an option for patients who have failed other forms of therapy, provided close follow-up is maintained for development of peripheral neuropathy.

The nurse's role in assessing alcohol use by older people.

Nurses have the potential to carry out health promotion activity related to alcohol use in a range of settings where older people receive care. The majority of the literature on alcohol use in later life has focused on abuse, especially on the more common risk of drug-alcohol interactions. In order to work effectively with older people in health prevention and education, nurses need to be knowledgeable about older people's patterns of drinking, the effects of alcohol on medication and the current evidence on the harm and benefits of alcohol to health. In carrying out assessments, a skillful approach needs to be adopted in questioning older clients on what some might regard as a sensitive issue. Screening tools for the detection of alcohol abuse in the general adult population may not be valid for use with older clients. Tools specific to the detection of alcohol abuse by older people will be considered.

The care of older people with a delirium in acute care settings.

This article suggests that nurses should play a major part in the screening, assessment and management of delirium in older people in acute settings.

The need for specialist nurses to work with older people.

This article is based on a comprehensive literature review undertaken by the Royal College of Nursing gerontological nursing programme on the development of specialist gerontological nursing practice (Schofield et al, 1998). The scope of the original review covered the development of specialist nursing, frameworks for practice, accreditation and regulation, role components and competencies, methods of evaluating the specialist role and fields of practice. The literature review's purpose was to inform work on the development of a specialist gerontological nursing BSc (Hons) degree by distance learning. This article focuses on the key findings of the literature review, setting out the potential for the introduction of specialist gerontological nurses in the UK.

Influenza vaccination.

Nurses have an important part to play in dispelling myths about influenza vaccination and in actively encouraging older people to attend for vaccination. Irene Schofield discusses the issues.

Promoting travel health for older people.

Older people are spending more time travelling for recreation than ever before. Irene Schofield considers what advice should be given to older clients to reduce any associated risks.

Influenza vaccination.

Nurses have an important part to play in dispelling myths about influenza vaccination and in actively encouraging older people to attend for vaccination. Irene Schofield discusses the issues.