Patients with hypoparathyroidism can present with concurrent basal ganglia calcifications (BGCs). The exact pathogenesis is unknown, although it is thought to relate to calcium-phosphate deposition from chronic hypocalcemia and hyperphosphatemia. We present the case of a 65-year-old man with known idiopathic primary hypoparathyroidism and concurrent extensive BGC. Thirty years after diagnosis, he presented with focal seizures despite a decade of stable intracranial calcifications on imaging. Serum calcium, phosphate, 25-hydroxyvitamin D, and parathyroid hormone levels were well controlled during this period. He was commenced on lifelong levetiracetam with subsequent seizure remission. Given the scarcity of literature surrounding focal seizures and BGC, it is essential to raise awareness in this area.
Importance: First-seizure clinics (FSCs) aim to deliver prompt specialist care to patients with new-onset undifferentiated seizure events. Objective: To determine whether FSC attendance and time to FSC are associated with subsequent health care utilization and mortality and to investigate factors associated with FSC nonattendance. Design, Setting, and Participants: This was a record-linkage, retrospective, cohort study of patients who booked appointments at 2 FSCs between 2007 and 2018. Patients' records were linked to state-wide administrative databases between 2000 and 2021. The setting comprised the FSCs of 2 major metropolitan public hospitals in Melbourne, Australia, providing national inpatient and outpatient adult epilepsy services. Of patients who booked appointments at the FSCs, those who were successfully linked for analysis were included in the study. Patients who recorded only canceled appointments were excluded from analysis of outcomes. Study data were analyzed from January 2000 to December 2021. Exposure: FSC attendance. Main Outcomes and Measures: Subsequent all-cause and seizure-related emergency department (ED) presentations and hospital admissions. Results: Of 10â¯162 patients with appointments at FSCs, 9392 were linked for analysis, with mean (SD) follow-up time 6.9 (2.8) years after FSC referral. A total of 703 patients were excluded. Among 9392 linked patients, 5398 were male (57.5%; mean [SD] age, 59.7 [11.2] years). FSC attendance was associated with reduced subsequent all-cause emergency presentations (adjusted incidence rate ratio [aIRR], 0.72; 95% CI, 0.66-0.79) and all-cause hospitalization (aIRR, 0.81; 95% CI, 0.75-0.88). Those who attended at the first-scheduled appointment, compared with those who attended only a rescheduled, delayed appointment, had reduced subsequent all-cause emergency presentations (aIRR, 0.83; 95% CI, 0.76-0.91), all-cause hospitalization (aIRR, 0.71; 95% CI, 0.65-0.79), seizure-related presentations (aIRR, 0.40; 95% CI, 0.33-0.49), and mortality (hazard ratio, 0.82; 95% CI, 0.69-0.98). Male sex was associated with nonattendance (adjusted relative risk [aRR], 1.12; 95% CI, 1.03-1.22), as were injury at emergency presentation (aRR, 1.12; 95% CI, 1.01-1.24), psychiatric comorbidity (aRR, 1.68; 95% CI, 1.55-1.81), previous seizure-related presentations (aRR, 1.35; 95% CI, 1.22-1.49), and delays (>14 days) between FSC referral and appointment (aRR, 1.35; 95% CI, 1.18-1.54). Hospitalization at referral was associated with reduced nonattendance (aRR, 0.80; 95% CI, 0.72-0.90), as were non-English language preference (aRR, 0.81; 95% CI, 0.69-0.94), distance greater than 6 mi from home to clinic (aRR, 0.85; 95% CI, 0.76-0.95), and physical comorbidity (aRR, 0.80; 95% CI, 0.72-0.89). Conclusions and Relevance: Results of this cohort study suggest that FSC attendance, particularly early attendance, was associated with reduced rates of subsequent hospital utilization. This knowledge may support adequately resourcing FSCs to improve equitable, timely access. Future study directions include assessing interventions that may support FSC attendance for at-risk groups.
Oral tumors are relatively common in dogs, and canine oral squamous cell carcinoma (COSCC) is the most prevalent oral malignancy of epithelial origin. COSCC is locally aggressive with up to 20% of patients showing regional or distant metastasis at the time of diagnosis. The treatment of choice most typically involves wide surgical excision. Although long-term remission is possible, treatments are associated with significant morbidity and can negatively impact functionality and quality of life. OSCCs have significant upregulation of the RAS-RAF-MEK-MAPK signaling axis, and we had previously hypothesized that small-molecule inhibitors that target RAS signaling might effectively inhibit tumor growth and progression. Here, we demonstrate that the MEK inhibitor trametinib, an FDA-approved drug for human cancers, significantly blocks the growth of several COSCC cell lines established from current patient tumor samples. We further show clinical evidence that the drug is able to cause significant tumor regression in some patients with spontaneously occurring COSCC. Given the limited treatment options available and the high rate of owner rejection of these offered options, these findings provide new hope that more acceptable treatment options may soon enter the veterinary clinic.
OBJECTIVE: To measure interobserver agreement for 4 functional tasks and their summed geriatric functional score (GFS) and correlate tasks and GFS with client-specific outcome measurements (CSOMs): Canine Brief Pain Inventory (CBPI) pain severity, CBPI pain interference, and Liverpool Osteoarthritis in Dogs. ANIMALS: 89 geriatric dogs were recruited between April and September 2023 from staff, friends, and clients of the Cornell University College of Veterinary Medicine with a median age of 11.0 years and weight of 26.4 kg. METHODS: Dogs underwent 4 sequential functional tests: timed up and go (TUG), cavallettis, figure 8s, and down to stands. Two observers independently scored each dog. The GFS was calculated based on the summed scores of the individual tests. Additional information collected included signalment, weight, measurements reflecting the comorbidities of aging (body condition score and muscle condition score), and CSOMs. RESULTS: Strong interrater agreement was found for all functional tests. The TUG in seconds (sTUG) and figure 8s demonstrated significant (P < .05) moderate to strong correlations to all CSOMs. The GFS showed similar significant correlations with all CSOMs except CBPI pain severity; however, when correlating individual tests to CSOMs, only figure 8s and TUG were significantly contributing to GFS results. Receiver operating characteristic curve analysis defined highly functional dogs as those completing the sTUG in under 3.83 seconds. The sTUG represented the best test for geriatric function given it was objective, reliable, correlated well to CSOMs, and could help identify highly functioning dogs. CLINICAL RELEVANCE: The sTUG appears to be the first practical and reliable functional test of canine geriatric mobility.
Human familial isolated pituitary adenoma (FIPA) has been linked to germline heterozygous mutations in the gene encoding the aryl hydrocarbon receptor-interacting protein (AIP, also known as ARA9, XAP2, FKBP16, or FKBP37). To investigate the hypothesis that AIP is a pituitary adenoma tumor suppressor via its role in aryl hydrocarbon receptor (AHR) signaling, we have compared the pituitary phenotype of our global null Aip (AipΔC) mouse model with that of a conditional null Aip model (Aipfx/fx) carrying the same deletion, as well as pituitary phenotypes of Ahr global null and Arnt conditional null animals. We demonstrate that germline AipΔC heterozygosity results in a high incidence of pituitary tumors in both sexes, primarily somatotropinomas, at 16 months of age. Biallelic deletion of Aip in Pit-1 cells (Aipfx/fx:rGHRHRcre) increased pituitary tumor incidence and also accelerated tumor progression, supporting a loss-of-function/loss-of-heterozygosity model of tumorigenesis. Tumor development exhibited sexual dimorphism in wildtype and Aipfx/fx:rGHRHRcre animals. Despite the role of AHR as a tumor suppressor in other cancers, the observation that animals lacking AHR in all tissues, or ARNT in Pit-1 cells, do not develop somatotropinomas argues against the hypothesis that pituitary tumorigenesis in AIP-associated FIPA is related to decreased activities of either the Ahr or Arnt gene products.
Purpose: Delays in outpatient specialist neurologist care for people with epilepsy are common despite recommendations for prompt access. There is evidence to suggest that there are interventions that can minimise waitlists and waiting time. However, little is known about whether such interventions can result in sustained improvements in waiting. The aim of this study was to determine the extent to which an intervention to reduce waiting in an epilepsy specialist outpatient clinic demonstrated sustained outcomes two years after the intervention was implemented. Methods: This observational study analysed routinely collected epilepsy clinic data over three study periods: pre-intervention, post-intervention and at two-year follow-up. The intervention, Specific Timely Assessment and Triage (STAT), combined a short-term backlog reduction strategy and creation of protected appointments for new referrals based on analysis of demand. After the initial intervention, there was no further active intervention in the following two years. The primary outcome was waiting measured by 1.) waiting time for access to a clinic appointment, defined as the number of days between referral and first appointment for all patients referred to the epilepsy clinic during the three study periods; and 2.) a snapshot of the number of patients on the waitlist at two time points for each of the three study periods. Results: Two years after implementing the STAT model in an epilepsy clinic, median waiting time from post-intervention to two-year follow-up was stable (52-51 days) and the interquartile range of days waited reduced from 37 to 77 days post-intervention to 45-57 days at two-year follow-up, with a reduction in the most lengthy wait times observed. After a dramatic reduction of the total number of patients on the waitlist immediately following the intervention, a small rise was seen at two years (n = 69) which remained well below the pre-intervention level (n = 582). Conclusion: The STAT model is a promising intervention for reducing waiting in an epilepsy clinic. While there was a small increase in the waitlist after two years, the median waiting time was sustained.
OBJECTIVE: This overview of systematic reviews aimed to appraise evidence regarding self-management strategies on health-related quality of life, self-efficacy, medication compliance, seizure status and psychosocial outcomes compared to usual care for people with epilepsy. METHODS: Databases were searched until September 2022 using MeSH terms included OVID Medline, Embase and Cochrane. Following application of eligibility criteria, data were extracted and quality of articles was assessed using the AMSTAR2 checklist. A narrative synthesis of evidence included certainty of evidence evaluated using a Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: The 12 selected reviews contained three meta-analyses and 91 unique primary studies. One review considered only epilepsy with intellectual disability and three considered paediatrics. Interventions included technologically-based interventions, small group discussion, or counselling and educational programs. There was high certainty evidence to suggest self-management is associated with improvement in health-related quality of life and moderate certainty evidence to suggest improvement in depression symptoms. There was low certainty evidence to suggest a modest reduction in negative health events and a minimal increase in the satisfaction with life. There was no evidence of benefit favouring self-management on measures of adherence epilepsy self-management, perception of self-efficacy, medication adherence or seizure status. SIGNIFICANCE: Despite high certainty evidence to suggest that self-management strategies for people with epilepsy improve health-related quality of life, benefits have not been demonstrated for outcomes that would be expected to be associated with these improvements, such as seizure status. These results provide support for self-management strategies to supplement usual care for people with epilepsy.
Epilepsy , Self-Management , Humans , Child , Quality of Life , Systematic Reviews as Topic , Epilepsy/drug therapy , Seizures
INTRODUCTION: Epilepsy is one of the most common neurological conditions worldwide. Despite many antiseizure medications (ASMs) being available, up to one-third of patients do not achieve seizure control. Preclinical studies have shown treatment with sodium selenate to have a disease-modifying effect in a rat model of chronic temporal lobe epilepsy (TLE). AIM: This randomised placebo-controlled trial aims to evaluate the antiseizure and disease-modifying effects of sodium selenate in people with drug-resistant TLE. METHODS: This will be a randomised placebo-controlled trial of sodium selenate. One hundred and twenty-four adults with drug-resistant TLE and ≥4 countable seizures/month will be recruited. Outcomes of interest will be measured at baseline, week 26 and week 52 and include an 8-week seizure diary, 24-hour electroencephalogram and cognitive, neuropsychiatric and quality of life measures. Participants will then be randomised to receive a sustained release formulation of sodium selenate (initially 10 mg three times a day, increasing to 15 mg three times a day at week 4 if tolerated) or a matching placebo for 26 weeks. OUTCOMES: The primary outcome will be a consumer codesigned epilepsy-Desirability of Outcome Rank (DOOR), combining change in seizure frequency, adverse events, quality of life and ASM burden measures into a single outcome measure, compared between treatment arms over the whole 52-week period. Secondary outcomes will compare baseline measures to week 26 (antiseizure) and week 52 (disease modification). Exploratory measures will include biomarkers of treatment response. ETHICS AND DISSEMINATION: The study has been approved by the lead site, Alfred Hospital Ethics Committee (594/20). Each participant will provide written informed consent prior to any trial procedures. The results of the study will be presented at national and international conferences, published in peer-reviewed journals and disseminated through consumer organisations. CONCLUSION: This study will be the first disease-modification randomised controlled trial in patients with drug-resistant TLE. TRIAL REGISTRATION NUMBER: ANZCTR; ACTRN12623000446662.
Drug Resistant Epilepsy , Epilepsy, Temporal Lobe , Adult , Humans , Animals , Rats , Selenic Acid , Epilepsy, Temporal Lobe/drug therapy , Quality of Life , Treatment Outcome , Drug Resistant Epilepsy/drug therapy , Seizures , Randomized Controlled Trials as Topic , Clinical Trials, Phase II as Topic
BACKGROUND: Cats commonly develop thyroid disease but little is known about the long-term biological variability of serum thyroid hormone and thyrotropin (thyroid-stimulating hormone; TSH) concentrations. OBJECTIVES: We aimed to determine the long-term biological variation of thyroid hormones and TSH in clinically healthy cats. METHODS: A prospective, observational study was carried out. Serum samples for analysis of total thyroxine (T4, by radioimmunoassay [RIA] and homogenous enzyme immunoassay [EIA]), triiodothyronine (T3 ), free T4 (by dialysis), and TSH were obtained every 8 weeks for 1 year from 15 healthy cats, then frozen until single-batch analysis. Coefficients of variation (CV) within individual cats ( CV I ) and among individual cats ( CV G ), as well as the variation between duplicates (ie, analytical variation [ CV A ]) were determined with restricted maximum likelihood estimation. The indices of individuality (IoI) and reference change values (RCVs) for each hormone were calculated. RESULTS: Some thyroid hormones showed similar (total T4 by EIA) or greater (TSH) interindividual relative to intraindividual variation resulting in intermediate to high IoI, consistent with previous studies evaluating the biological variation of these hormones weekly for 5-6 weeks. By contrast, total T4 (by RIA) and free T4 had a low IoI. Total T3 had a high ratio of CV A to CV I ; therefore, interindividual variation could not be distinguished from analytical variation. No seasonal variability in the hormones could be demonstrated. CONCLUSIONS: Clinicians might improve the diagnosis of feline thyroid disease by establishing baseline concentrations for analytes with intermediate-high IoI (total T4, TSH) for individual cats and applying RCVs to subsequent measurements.
Cat Diseases , Thyroid Diseases , Cats , Animals , Prospective Studies , Thyroid Hormones , Thyroxine , Thyroid Diseases/veterinary , Thyrotropin
BACKGROUND: Delayed access to outpatient care may negatively impact on health outcomes. We aimed to evaluate implementation of the Specific Timely Appointments for Triage (STAT) model of access in an epilepsy clinic to reduce a long waitlist and waiting time. METHODS: This study is an intervention study using pre-post comparison and an interrupted time series analysis to measure the effect of implementation of the STAT model to an epilepsy clinic. Data were collected over 28 months to observe the number of patients on the waitlist and the waiting time over three time periods: 12 months prior to implementation of STAT, ten months during implementation and six months post-intervention. STAT combines one-off backlog reduction with responsive scheduling that protects time for new appointments based on historical data. The primary outcomes were the number of patients on the waitlist and the waiting time across the three time periods. Secondary outcomes evaluated pre- and post-intervention changes in number of appointments offered weekly, non-arrival and discharge rates. RESULTS: A total of 938 patients were offered a first appointment over the study period. The long waitlist was almost eliminated, reducing from 616 during the pre-intervention period to 11 post-intervention (p = 0.002), but the hypothesis that waiting time would decrease was not supported. The interrupted time series analysis indicated a temporary increase in waiting time during the implementation period but no significant change in slope or level in the post- compared to the pre-intervention period. Direct comparison of the cohort of patients seen in the pre- and post-intervention periods suggested an increase in median waiting time following the intervention (34 [IQR 25-86] to 46 [IQR 36-61] days (p = 0.001)), but the interquartile range reduced indicating less variability in days waited and more timely access for the longest waiters. CONCLUSIONS: The STAT model was implemented in a specialist epilepsy outpatient clinic and reduced a large waitlist. Reductions in the waitlist were achieved with little or no increase in waiting time. The STAT model provides a framework for an alternative way to operate outpatient clinics that can help to ensure that all people referred are offered an appointment in a timely manner.
Epilepsy , Outpatients , Humans , Triage , Ambulatory Care Facilities , Ambulatory Care , Epilepsy/therapy
OBJECTIVE: To report the complication rate of dogs undergoing oral oncological surgery when using a bone-cutting piezoelectric unit for osteotomies. CLINICAL PRESENTATION AND PROCEDURES: Retrospective cohort evaluation of medical records from 2012 through 2022 for canine patients that underwent mandibulectomy or maxillectomy for the treatment of oral neoplasia at the Companion Animal Hospital at Cornell University. Cases were included if osteotomy was performed using a piezoelectric unit. Medical records were then reviewed for documentation of intraoperative hemorrhage and administration of blood products. RESULTS: 41 maxillectomies and 57 mandibulectomies met the inclusion criteria (98 in total). Only 1 (1.02%) case was associated with excessive surgical bleeding requiring administration of blood products. CLINICAL RELEVANCE: Results of this study show that intraoperative hemorrhage requiring the use of blood products during or immediately after a mandibulectomy or maxillectomy is rare when using a piezoelectric unit to perform osteotomies, and is substantially lower than that previously reported when using oscillating saws or other bone-cutting devices for maxillectomies.
Dog Diseases , Mouth Neoplasms , Dogs , Animals , Mandibular Osteotomy/veterinary , Retrospective Studies , Osteotomy/adverse effects , Osteotomy/veterinary , Craniotomy/veterinary , Mouth Neoplasms/surgery , Mouth Neoplasms/veterinary , Dog Diseases/surgery
Improved quality of life (QoL) is an important outcome goal following epilepsy surgery. This study aims to quantify change in QoL for adults with drug-resistant epilepsy (DRE) who undergo epilepsy surgery, and to explore clinicodemographic factors associated with these changes. We conducted a systematic review and meta-analysis using Medline, Embase, and Cochrane Central Register of Controlled Trials. All studies reporting pre- and post-epilepsy surgery QoL scores in adults with DRE via validated instruments were included. Meta-analysis assessed the postsurgery change in QoL. Meta-regression assessed the effect of postoperative seizure outcomes on postoperative QoL as well as change in pre- and postoperative QoL scores. A total of 3774 titles and abstracts were reviewed, and ultimately 16 studies, comprising 1182 unique patients, were included. Quality of Life in Epilepsy Inventory-31 item (QOLIE-31) meta-analysis included six studies, and QOLIE-89 meta-analysis included four studies. Postoperative change in raw score was 20.5 for QOLIE-31 (95% confidence interval [CI] = 10.9-30.1, I2 = 95.5) and 12.1 for QOLIE-89 (95% CI = 8.0-16.1, I2 = 55.0%). This corresponds to clinically meaningful QOL improvements. Meta-regression demonstrated a higher postoperative QOLIE-31 score as well as change in pre- and postoperative QOLIE-31 score among studies of cohorts with higher proportions of patients with favorable seizure outcomes. At an individual study level, preoperative absence of mood disorders, better preoperative cognition, fewer trials of antiseizure medications before surgery, high levels of conscientiousness and openness to experience at the baseline, engagement in paid employment before and after surgery, and not being on antidepressants following surgery were associated with improved postoperative QoL. This study demonstrates the potential for epilepsy surgery to provide clinically meaningful improvements in QoL, as well as identifies clinicodemographic factors associated with this outcome. Limitations include substantial heterogeneity between individual studies and high risk of bias.
Drug Resistant Epilepsy , Epilepsy , Adult , Humans , Quality of Life , Epilepsy/surgery , Seizures , Antidepressive Agents
OBJECTIVE: This study was undertaken to analyze phenotypic features of a cohort of patients with protracted CLN3 disease to improve recognition of the disorder. METHODS: We analyzed phenotypic data of 10 patients from six families with protracted CLN3 disease. Haplotype analysis was performed in three reportedly unrelated families. RESULTS: Visual impairment was the initial symptom, with onset at 5-9 years, similar to classic CLN3 disease. Mean time from onset of visual impairment to seizures was 12 years (range = 6-41 years). Various seizure types were reported, most commonly generalized tonic-clonic seizures; focal seizures were present in four patients. Progressive myoclonus epilepsy was not seen. Interictal electroencephalogram revealed mild background slowing and 2.5-3.5-Hz spontaneous generalized spike-wave discharges. Additional interictal focal epileptiform discharges were noted in some patients. Age at death for the three deceased patients was 31, 31, and 52 years. Molecular testing revealed five individuals were homozygous for c.461-280_677 + 382del966, the "common 1-kb" CLN3 deletion. The remaining individuals were compound heterozygous for various combinations of recurrent pathogenic CLN3 variants. Haplotype analysis demonstrated evidence of a common founder for the common 1-kb deletion. Dating analysis suggested the deletion arose approximately 1500 years ago and thus did not represent cryptic familial relationship in this Australian cohort. SIGNIFICANCE: We highlight the protracted phenotype of a disease generally associated with death in adolescence, which is a combined focal and generalized epilepsy syndrome with progressive neurological deterioration. The disorder should be suspected in an adolescent or adult patient presenting with generalized or focal seizures preceded by progressive visual loss. The common 1-kb deletion has been typically associated with classic CLN3 disease, and the protracted phenotype has not previously been reported with this genotype. This suggests that modifying genetic factors may be important in determining this somewhat milder phenotype and identification of these factors should be the subject of future research.
Epilepsy, Generalized , Neuronal Ceroid-Lipofuscinoses , Humans , Neuronal Ceroid-Lipofuscinoses/complications , Neuronal Ceroid-Lipofuscinoses/diagnosis , Neuronal Ceroid-Lipofuscinoses/genetics , Australia , Seizures/diagnosis , Genotype , Membrane Glycoproteins/genetics , Molecular Chaperones/genetics
BACKGROUND: Acute traumatic coagulopathy (ATC) has many phenotypes and varying morbidity and mortality. The MA-R ratio, calculated from the admission thromboelastogram, serves as a biomarker to identify 1 phenotype of ATC and has previously been associated with significant derangements in the inflammatory response. This study evaluates outcomes related to abnormal MA-R ratios, including inflammatory responses, in a heterogeneous patient population. STUDY DESIGN: Patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) dataset were included. The MA-R ratio was calculated from admission thromboelastography, with a CRITICAL ratio defined as 11 or less. Key inflammatory mediators were identified as a priori. Cytokine expression was assessed during 24 hours using multivariable logistic regression. RESULTS: Significant elevations in the proinflammatory cytokines IL-1b, IL-6, and IL-8, as well as in the chemokines eotaxin, IFN-γ-induced protein 10, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1ß, persisted during the first 24 hours. CRITICAL patients had significantly lower survival at 1, 3, 6, 12, and 18 hours and demonstrated significantly increased ARDS (odds ratio [OR] 1.817, 95% CI 1.082 to 3.051, p = 0.0239). CRITICAL patients had fewer ICU-free days (CRITICAL, 10 days, interquartile range [IQR] 0 to 25; vs NORMAL, 22 days, IQR 4 to 26, p < 0.0001) and fewer ventilator-free days (CRITICAL, 15 days, IQR 0 to 28; vs NORMAL, 26 days, IQR 9 to 28, p < 0.0001). CRITICAL patients were protected against systemic inflammatory response (OR 0.521, 95% CI 0.322 to 0.816, p = 0.0044). CONCLUSIONS: The subtype of ATC identified by the low MA-R ratio is associated with significant elevations in multiple proinflammatory cytokines at admission. Early mortality remains elevated in the CRITICAL group, in part due to coagulopathy. The MA-R ratio at admission is associated with a particularly morbid type of coagulopathy, associated with significant alterations in the inflammatory response after severe injury in heterogeneous patient populations.
Blood Coagulation Disorders , Thrombelastography , Humans , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , Blood Platelets , Cytokines , Inflammation/etiology
OBJECTIVE: To retrospectively investigate the safety of canine therapeutic IA injections, describing and correlating adverse events with the number of injections per visit, joint injected, signalment, body condition score, type, and volume of injectate. SAMPLE: There were 505 joint injections across 283 visits for 178 client-owned dogs, including the shoulder, elbow, carpus, hip, stifle, tarsus, and metacarpophalangeal. PROCEDURES: A search was performed of the Cornell University Hospital for Animals medical records for relevant data, identifying dogs treated with therapeutic joint injections and rechecked between 2010 and 2022. RESULTS: Minor complications were noted in 70 of 283 visits and included transient soreness (18.4%, lasting a median of 2 days; range, 1 to 20 days) and gastroenteritis (6.8%). One case of septic arthritis (1/505 joints), which possessed risks of a hematogenous source, was the only potential major complication. Soreness was not correlated with the number of joints injected per visit. Larger volumes of injectate normalized to body size were more likely to be associated with transient soreness in the stifle and tarsus. Across injectates, only stem cells had significantly increased odds of soreness. Gastroenteritis was not associated with the type of injectate. CLINICAL RELEVANCE: Therapeutic joint injections in dogs are safe, with an extremely low risk of major adverse effects. Transient soreness is a commonly expected minor adverse event. The use of stem cells or larger injectate volumes (confined to the stifle and smaller distal joints) may be more likely to invoke discomfort.
Arthritis, Infectious , Dog Diseases , Elbow Joint , Dogs , Animals , Retrospective Studies , Stifle , Arthritis, Infectious/veterinary
To determine whether increased precipitation in the months before diagnosis is predictive of Lyme nephritis in dogs, a symmetrical bidirectional case-crossover study was performed on 87 dogs with presumptive Lyme nephritis. Cases were geographically linked to the nearest precipitation monitoring station, and monthly total precipitation for the 4 mo preceding diagnosis was compared to monthly total precipitation 1 yr before and 1 yr after. Breeds affected included Labrador retrievers (n = 31), mixed-breed dogs (n = 19), and golden retrievers (n = 10), with a possible seasonal bimodal peak in spring and fall. In age-adjusted analysis, each additional inch of precipitation 3 mo before diagnosis was associated with an increase in the odds of developing Lyme nephritis (odds ratio 1.13, 95% confidence interval 1.01-1.25). The results suggest that increased precipitation is a possible risk factor for Lyme nephritis in dogs. These findings may provide useful information for the accurate diagnosis of dogs with protein-losing nephropathy and may guide future studies of risk factors for Lyme nephritis. The methodology employed here reinforces the concept that case-crossover designs have utility beyond acute exposures and outcomes and offer an attractive alternative for studies in companion animals.
Dog Diseases , Lyme Disease , Nephritis , Dogs , Animals , Dog Diseases/etiology , Dog Diseases/diagnosis , Cross-Over Studies , Nephritis/diagnosis , Nephritis/veterinary , Risk Factors , Lyme Disease/veterinary , Lyme Disease/diagnosis
OBJECTIVES: People with epilepsy have a higher prevalence of medical and psychiatric comorbidities compared to the general population. Comorbidities are associated with poor epilepsy outcomes, and there have been recommendations for screening and early identification to improve clinical management. Data from 'First Seizure Clinics' (FSCs) with expert epileptological review can inform about disorders already present at the point of diagnosis of epilepsy or unprovoked seizures. Here, we aimed to describe pre-existing conditions with a focus on psychiatric, substance use, cardiac, neurological, and cancer health domains. METHODS: We included 1383 adults who received a new diagnosis of epilepsy or unprovoked seizures at Austin Hospital (AH) or Royal Melbourne Hospital (RMH) (Australia) FSCs from 2000 to 2010. Data were audited from FSC records, primarily detailed interviews undertaken by epileptologists. Logistic regression examined age distribution and other risk factors. RESULTS: The median age at FSC presentation was 37 years (IQR 26-53, range 18-94). Pre-existing conditions were reported by 40 %; from 32 % in the youngest group (18-30 years) to 53 % in the oldest (65+ years). Psychiatric (18 %) and substance use (16 %) disorders were most common, with higher prevalence among patients 18 to 65 years of age compared to those older than 65 years (p < 0.001). Cardiac, neurological, or cancer conditions were reported by 3-6 %, most often amongst those older than 65 years (p < 0.01). Eight percent (n = 112) reported disorders in >1 health domain. The commonest combination was a psychiatric condition with substance use disorder. Of the sixty-two patients reporting this combination, 61 were ≤65 years of age. CONCLUSIONS: Pre-existing health conditions are present in a substantial proportion of patients diagnosed with epilepsy or unprovoked seizures. Disorders are highest amongst elders, but one-third of younger adults also reported positive histories. These are predominantly psychiatric and/or substance use disorders, conditions strongly associated with poor outcomes in the general population. These findings inform post-diagnosis planning and management, as well as research examining post-diagnostic outcomes and associations between comorbidities and epilepsy.
Epilepsy , Mental Disorders , Adult , Humans , Aged , Preexisting Condition Coverage , Epilepsy/complications , Epilepsy/diagnosis , Epilepsy/epidemiology , Seizures/diagnosis , Comorbidity , Mental Disorders/diagnosis , Mental Disorders/epidemiology
BACKGROUND: Biological variation helps determine whether population-based or subject-based reference intervals are more appropriate to assess changes in serial analytical values. Previous studies have investigated the biological variation of biochemical analytes weekly or with variable frequency over 5-14 weeks in cats, but none have considered biological variation at less frequent intervals over 1 year. OBJECTIVES: We aimed to evaluate the long-term biological variation of 19 biochemical analytes in clinically healthy cats. METHODS: A prospective, observational study in which 15 clinically healthy, client-owned cats were sampled for serum biochemical analyses every 8 weeks for 1 year. Frozen serum samples were single-batch analyzed. Restricted maximum likelihood estimation was used to determine the coefficients of variation (CV), describing variation within each cat, between cats, and the analytical variation. These CVs were used to determine the indices of individuality and reference change values (RCVs). RESULTS: Albumin, alkaline phosphatase, creatine kinase, and globulin had high indices of individuality, indicating that they are best evaluated by RCVs. Phosphorus, potassium, chloride, sodium, symmetric dimethylarginine, and total CO2 had low indices of individuality, indicating that population-based reference intervals are appropriate. Alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, calcium, cholesterol, creatinine, glucose, total bilirubin, and total protein had intermediate indices of individuality, indicating that RCVs may provide additional insight into the interpretation of analyte measurements beyond the population-based reference intervals. CONCLUSIONS: For many analytes, the biological variation detected was similar to that reported in prior studies. Clinicians should consider the biological variation of analytes to best interpret clinically relevant changes in serial analyte measurements.
Cholesterol , Specimen Handling , Cats , Animals , Prospective Studies , Specimen Handling/veterinary , Blood Urea Nitrogen , Reference Values , Blood Chemical Analysis/veterinary
BACKGROUND: Improved methodology to measure acute phase proteins and determination of lipoprotein particle-size distribution (PSD) could be clinically useful in dogs with systemic inflammatory processes. OBJECTIVES: Evaluate an immunoturbidometric assay for serum amyloid A (SAA) and lipoprotein PSD in dogs with sepsis, nonseptic systemic inflammation, and in healthy controls. Correlate dyslipidemic changes with SAA and C-reactive protein (CRP) concentrations. ANIMALS: Twenty-five dogs with sepsis, 15 dogs with nonseptic systemic inflammation, and 22 healthy controls. METHODS: Prospective, case-control study. Variables included SAA, CRP, and electrophoretic subfractionation of high- and low-density lipoproteins (HDL, LDL). Continuous variables were compared using ANOVA or Kruskal-Wallis tests with linear regression or Spearman's rank correlation used to assess relationships between variables. RESULTS: Median SAA and CRP concentrations were greater in dogs with sepsis (SAA 460 mg/L, interquartile range [IQR] 886 mg/L; CRP 133.2 mg/L, IQR 91.6 mg/L) and nonseptic inflammation (SAA 201 mg/L, IQR 436 mg/L; CRP 91.1 mg/L, IQR 88.6 mg/L) compared to healthy dogs (SAA 0.0 mg/L, IQR 0.0 mg/L; CRP 4.9 mg/L, IQR 0.0 mg/L) P < .0001. A cutoff of >677.5 mg/L SAA was 43.2% sensitive and 92.3% specific for sepsis. Low-density lipoprotein was higher in dogs with sepsis 29.6%, (mean, SD 14.6) compared to 14.4% (mean, SD 5.6) of all lipoproteins in healthy controls (P = .005). High-density lipoprotein was not associated with CRP but was negatively correlated with SAA (rs -0.47, P < .0001). Subfractions of LDL and HDL differed between groups (all P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of SAA using the immunoturbidometric assay evaluated in this study and lipoprotein PSD in dogs with inflammation might help distinguish septic from nonseptic causes of inflammation.
Dog Diseases , Sepsis , Acute-Phase Proteins , Acute-Phase Reaction/veterinary , Animals , Biomarkers , C-Reactive Protein/analysis , Case-Control Studies , Dogs , Inflammation/veterinary , Lipoproteins , Particle Size , Prospective Studies , Sepsis/veterinary , Serum Amyloid A Protein/metabolism
Proteins, such as the Ah receptor (AHR), hold potential as sensors to detect ligands in environmental and biological samples, and may also serve as tools to regulate biosynthetic and industrial processes. The AHR is also a prototype system for the PAS superfamily that can sense and mediate adaptation to signals as diverse as light, voltage, oxygen and an array of small molecules. The yeast, S. cerevisiae, has proven to be an important model to study the signal transduction of sensors like the AHR because of its ease of use, numerous available strategies for genetic manipulation, and capacity for heterologous expression. To better understand the utility of sensor proteins as components of yeast detection systems, we characterized a chimeric AHR-LexA system that drives expression from a Lex operator (LexO) driven, beta-galactosidase (ß-Gal) reporter. In this report, we demonstrate that improvements in assays sensitivity and pharmacology can arise from the careful optimization of yeast growth phase and the duration of ligand exposure. We also report that the coexpression of heterotypic modifiers from mammalian cells (e.g., the ARA9 and ARA3 proteins), can improve yeast assay performance. We propose that complementing these assay improvements with previously reported yeast mutations described by others will expand the utility of the AHR for biotechnology applications.
