Epidemiology of myasthenia gravis in France: A retrospective claims database study (STAMINA).

BACKGROUND: The objectives of this observational study were to report the incidence and prevalence of myasthenia gravis (MG) in France, describe patients' characteristics and treatment patterns, and estimate mortality. METHODS: A historical cohort analysis was performed using the French National Health Data System (SNDS) database between 2008 and 2020. Patients with MG were identified based on ICD-10 codes during hospitalization and/or long-term disease (ALD) status, which leads to a 100% reimbursement for healthcare expenses related to MG. The study population was matched to a control group based on age, sex and region of residence. RESULTS: The overall incidence of MG was estimated at 2.5/100,000 in 2019 and the overall prevalence at 34.2/100,000. The mean age was 58.3 years for incident patients and 58.6 for prevalent patients. Among patients with MG, 57.1% were women. In the first year after identification of MG, acetylcholinesterase inhibitors were the most commonly used treatments (87.0%). Corticosteroids were delivered to 58.3% of patients, intravenous immunoglobulin to 34.4%, and azathioprine to 29.9%. Additionally, 8% of patients underwent thymectomy. The proportions of patients with exacerbations and crises were 59.7% and 13.5% respectively in the first year after MG identification. All-cause mortality was significantly higher in patients with MG compared to matched controls (HR=1.82 (95% CI [1.74;1.90], P<0.0001)). CONCLUSION: In this study, the incidence and prevalence of MG estimated in France were found to be higher than previously reported. Most exacerbations and crises occurred within the first year after MG identification. MG was associated with increased mortality compared to a control population matched on age, gender, and geographical region.

Ultrasonographic measurement of caudal vena cava to aorta ratio during fluid resuscitation of dogs with spontaneous circulatory shock.

OBJECTIVES: To describe the change in the caudal vena cava to aorta ratio (CVC:Ao) ratio during fluid resuscitation of circulatory shock in dogs and compare these results with those of the physical examination and blood lactate. MATERIALS AND METHODS: Perfusion parameters and blood lactate were recorded at admission. An abdominal point-of-care ultrasound protocol was performed, during which the caudal vena cava to aorta ratio was measured on the spleno-renal view. Measurements were performed within 5 minutes before and after a 10 mL/kg crystalloid fluid bolus. Investigators were not blinded to therapeutic interventions. RESULTS: Twenty-nine dogs with physical signs of circulatory shock were enrolled. Caudal vena cava to aorta ratios were below reference interval in 28 of 29 dogs. After bolus administration, median caudal vena cava diameter increased by 0.14 cm (0.69 to 0.83 cm) and median aorta diameter increased by 0.03 cm (0.87 to 0.90 cm) and caudal vena cava to aorta ratio returned to within reference range in 65% of dogs (13/29). Bolus administration was associated with an increase in median caudal vena cava to aorta ratio of 0.10 (95% CI:0.05 to 0.16, P=0.0005). Blood lactate did not change significantly. Heart rate and capillary refill time decreased significantly after fluid bolus (heart rate: estimate=-19 bpm, 95% CI:-30 to -8, P=0.002; capillary refill time: estimate=-1.0 s, 95% CI:-1.3 to -0.7, P < 0.0001). CLINICAL SIGNIFICANCE: In this population of dogs with circulatory shock, the caudal vena cava to aorta ratio significantly increased after a fluid bolus. Future studies that implement blinding of the outcome assessors are warranted to confirm these findings.

Impact of flow and temperature on non-dyspnoeic dogs' tolerance undergoing high-flow oxygen therapy.

OBJECTIVES: To prospectively describe the impact of gas flow rate and temperature on dog's tolerance of high-flow nasal oxygen therapy during recovery from anaesthesia, hypothesizing that higher flow rates and temperatures will decrease tolerance. MATERIALS AND METHODS: Twelve non-dyspnoeic client-owned dogs recovering from general anaesthesia were included in this study. After extubation, a nasal cannula was positioned and high-flow nasal oxygen therapy was initiated. Two flow rates (two or four time the theoretical minute ventilation: HF2 and HF4), each of them combined with two temperatures (31 and 37°C: T31 and T37), were randomly applied (four conditions per dog). For each condition, cardiovascular and respiratory parameters (heart rate, respiratory rate, systolic arterial blood pressure and pulse oximeter oxygen saturation), sedation score and tolerance score were recorded at initiation (T0 ) and after 10 minutes of accommodation (T10 ). RESULTS: Sedation scores were not significantly different between the four conditions. Cardiovascular and respiratory parameters were not significantly different between any condition at both T0 and T10 . Tolerance scores were good and not significantly different between any flow rate or temperature (HF2-T31: 4 (2-4), HF4-T31: 4 (2-4), HF2-T37: 4 (2-4), HF4-T37: 4 (1-4)). CLINICAL SIGNIFICANCE: The gas flow rates and temperatures studied have no impact on tolerance during the recovery period of non-dyspnoeic dogs, and high-flow nasal cannula is well tolerated. Further studies are required to confirm these results in dyspnoeic dogs.

[Association between psychiatric comorbidities and hospital length of stay in post-emergency internal medicine patients]. / Association des comorbidités psychiatriques avec la durée de séjour des patients en médecine interne d'aval des urgences.

INTRODUCTION: Patients with psychiatric disorders suffer from a higher rate of somatic disorders than those without psychiatric disorder, often inappropriately managed. Our study aimed to describe patients with psychiatric comorbidity in post-emergency internal medicine units and to compare their length of hospital stay to patients without psychiatric disease. METHODS: This French cross sectional study used the data warehouse of the greater Paris hospitals. It included, all patients hospitalized through the emergency department in 9 internal medicine departments during the year 2017. Psychiatric disorders and the burden of somatic disorders (Charlson score) were determined through diagnostic coding. Charlson score and hospital length of stay were compared between patients with and without psychiatric comorbidity. RESULTS: In total, 8981 hospital stays (8001 patients) were included, 1867 (21%) with psychiatric comorbidity. After adjusting for age, gender, hospital and main diagnosis, the Charlson score was on average 0.68 higher in the psychiatric comorbidity group (P<0.001) and the length of hospital stay was 30% higher after further adjustment on the Charlson score (P<0.001). These differences were consistent for each main diagnosis. CONCLUSION: Patients with psychiatric comorbidity are frequent in post-emergency internal medicine wards. They experience longer hospital stays, only partly related with a higher burden of somatic disorders. Special attention should be paid to this vulnerable population.

Prospective pilot study for evaluation of high-flow oxygen therapy in dyspnoeic dogs: the HOT-DOG study.

OBJECTIVES: To describe the use, effectiveness and tolerance of high-flow oxygen therapy in dyspnoeic dogs. MATERIALS AND METHODS: Prospectively, dogs in acute respiratory distress admitted to an intensive care unit between January and May 2018 that failed to respond to nasal oxygen therapy and medical stabilisation after 30 minutes were transitioned to high-flow oxygen therapy. High-flow oxygen therapy, delivered an inspired oxygen fraction of 100% using an air/oxygen blender, active humidifier, single warmed tube and specific nasal cannula. Respiratory rate, pulse oximetry (SpO2 ), heart rate and a tolerance score were assessed every 15 minutes from T0 (under nasal oxygen) to 1 hour (T60 ), and PaO2 and PaCO2 at T0 and T60 . Complications were recorded for each dog. RESULTS: Eleven dogs were included. At T60 , PaO2 , flow rate and SpO2 were significantly greater than at T0 (171 ± 123 versus 73 ± 24 mmHg; P=0.015; 18 ±12 L/minute versus 3.2 ± 2.0 L/minute, P<0.01; 97.7 ±2.3% versus 91.6 ±7.2%, P=0.03, respectively). There was no significant difference in PaCO2 , respiratory rate or heart rate between T0 and T60 . Tolerance was excellent, and there were no complications. CLINICAL SIGNIFICANCE: High-flow oxygen therapy improves markers of oxygenation in dyspnoeic dogs and is an effective means to deliver oxygen with comfort and minimal complications.

Does childhood experience of attention-deficit hyperactivity disorder symptoms increase sleep/wake cycle disturbances as measured with actigraphy in adult patients with bipolar disorder?

Childhood attention-deficit hyperactivity disorder (ADHD) is a common precursor of adult bipolar disorders (BD). Furthermore, actigraphy studies demonstrate that each disorder may be associated with abnormalities in sleep and activity patterns. This study investigates whether the presence or absence of self-reported childhood experiences of ADHD symptoms is associated with different sleep and activity patterns in adults with BD. A sample of 115 euthymic adult patients with BD was assessed for childhood ADHD symptoms using the Wender Utah Rating Scale (WURS) and then completed 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and variability and daytime activity were compared between BD groups classified as ADHD+ (n = 24) or ADHD- (n = 91), defined according to established cutoff scores for the WURS; then we examined any associations between sleep-wake cycle parameters and ADHD dimensions (using the continuous score on the WURS). Neither approach revealed any statistically significant associations between actigraphy parameters and childhood ADHD categories or dimensions. We conclude that the sleep and activity patterns of adult patients with BD do not differ according to their self-reported history of ADHD symptoms. We discuss the implications of these findings and suggest how future studies might confirm or refute our findings.

Which actigraphic variables optimally characterize the sleep-wake cycle of individuals with bipolar disorders?

OBJECTIVE: To examine which combination of objectively measured actigraphy parameters best characterizes the sleep-wake cycle of euthymic individuals with bipolar disorder (BD) compared with healthy controls (HC). METHODS: Sixty-one BD cases and 61 matched HC undertook 21 consecutive days of actigraphy. Groups were compared using discriminant function analyses (DFA) that explored dimensions derived from mean values of sleep parameters (Model 1); variability of sleep parameters (2); daytime activity (3); and combined sleep and activity parameters (4). Exploratory within-group analyses examined characteristics associated with misclassification. RESULTS: After controlling for depressive symptoms, the combined model (4) correctly classified 75% cases, while the sleep models (1 and 2) correctly classified 87% controls. The area under the curve favored the combined model (0.86). Age was significantly associated with misclassification among HC, while a diagnosis of BD-II was associated with an increased risk of misclassifications of cases. CONCLUSION: Including sleep variability and activity parameters alongside measures of sleep quantity improves the characterization of cases of euthymic BD and helps distinguish them from HC. If replicated, the findings indicate that traditional approaches to actigraphy (examining mean values for the standard set of sleep parameters) may represent a suboptimal approach to understanding sleep-wake cycles in BD.

Sonographic assessment of volaemia: development and validation of a new method in dogs.

OBJECTIVES: The aims of this study were to describe a method for the sonographic assessment of volaemia, to determinate inter- and intra-operator variability and to assess the ability to detect blood loss after blood donation in healthy dogs. MATERIALS AND METHODS: The left kidney was identified in a spleno-renal view, and transverse views of the caudal vena cava and aorta were obtained in 12 dogs. Vessel diameters were measured in B-mode, in duplicate by two operators, and the caudal vena cava:aorta ratio was calculated. Intra- and inter-operator variabilities were assessed using a Bland-Altman method by plotting the differences between the repeated measurements obtained from the same subject by the same operator and by the two operators against their means. Before and after blood donation measurements were compared using paired t-tests or one-sample t-tests, if appropriate. RESULTS: Intra- and inter-operator variability was within the limit of agreement for the vast majority of measurements. After a blood donation of 9·8 ±2·2 mL/kg, the mean aorta measurements were not significantly different from those obtained before blood donation (1·11 versus 1·10, P=0·28), whereas the mean caudal vena cava measurements and caudal vena cava:aorta ratios were significantly lower (1·28 versus 1·01, P<0·0001; 1·17 versus 1·01, P=0·0001, respectively). CLINICAL SIGNIFICANCE: The low intra- and inter-operator variabilities in the caudal vena cava, aorta and caudal vena cava:aorta ratio measurements support their reliability and operator independency. The sonographic assessment of volaemia appears to be a promising non-invasive, repeatable point-of-care ultrasound protocol for assessment and monitoring of blood loss. Further studies are needed to assess the sonographic assessment of volaemia protocol in spontaneously bleeding dogs.

Pre- and Post-Transfusion Alloimmunization in Dogs Characterized by 2 Antiglobulin-Enhanced Cross-match Tests.

BACKGROUND: When dogs are transfused, blood compatibility testing varies widely but may include dog erythrocyte antigen (DEA) 1 typing and rarely cross-matching. OBJECTIVES: Prospective study to examine naturally occurring alloantibodies against red blood cells (RBCs) and alloimmunization by transfusion using 2 antiglobulin-enhanced cross-match tests. ANIMALS: Eighty client-owned anemic, 72 donor, and 7 control dogs. METHODS: All dogs were typed for DEA 1 and some also for DEA 4 and DEA 7. Major cross-match tests with canine antiglobulin-enhanced immunochromatographic strip and gel columns were performed 26-129 days post-transfusion (median, 39 days); some dogs had an additional early evaluation 11-22 days post-transfusion (median, 16 days). Plasma from alloimmunized recipients was cross-matched against RBCs from 34 donor and control dogs. RESULTS: The 2 cross-match methods gave entirely concordant results. All 126 pretransfusion cross-match results for the 80 anemic recipients were compatible, but 54 dogs died or were lost to follow up. Among the 26 recipients with follow-up, 1 dog accidently received DEA 1-mismatched blood and became cross-match-incompatible post-transfusion. Eleven of the 25 DEA 1-matched recipients (44%) became incompatible against other RBC antigens. No naturally occurring anti-DEA 7 alloantibodies were detected in DEA 7- dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The antiglobulin-enhanced immunochromatographic strip cross-match and laboratory gel column techniques identified no naturally occurring alloantibodies against RBC antigens, but a high degree of post-transfusion alloimmunization in dogs. Cross-matching is warranted in any dog that has been previously transfused independent of initial DEA 1 typing and cross-matching results before the first transfusion event.

Hemorrhagic, Hemostatic, and Thromboelastometric Disorders in 35 Dogs with a Clinical Diagnosis of Leptospirosis: A Prospective Study.

BACKGROUND: Leptospirosis in dogs is occasionally associated with a hemorrhagic syndrome, the pathophysiology of which is not fully understood. HYPOTHESIS/OBJECTIVES: To characterize hematologic, hemostatic, and thromboelastometric abnormalities in dogs with leptospirosis and to study their association with hemorrhagic diatheses and outcomes. ANIMALS: Thirty-five client-owned dogs. METHODS: A prospective observational single cohort study was conducted. Results from the CBC, coagulation tests (prothrombin, activated partial thromboplastin and thrombin times, fibrinogen, fibrin(ogen) degradation products, and D-dimer concentrations), rotational thromboelastometry (TEM), signalment, hemorrhagic diatheses, occurrence of disseminated intravascular coagulation (DIC) at admission, and survival to discharge were recorded. RESULTS: The most common hematologic and hemostatic abnormalities were anemia (30/35), thrombocytopenia (21/35), and hyperfibrinogenemia (15/35). Eight dogs were diagnosed with DIC. A normal TEM profile was found in 14 dogs, a hypercoagulable profile in 14 dogs, and a hypocoagulable profile in 7 dogs. The 8 dogs with hemorrhagic diatheses at admission had significantly decreased platelet counts (P = .037) and increased D-dimer concentrations (P = .015) compared with other dogs. Dogs with a hypocoagulable profile exhibited more hemorrhagic diatheses compared with the dogs that had normal and hypercoagulable profiles (P = .049). The mortality rate was lower in dogs with a hypercoagulable profile than in those with a hypocoagulable profile (21% vs 57%; P = .043). Disseminated intravascular coagulation was not a significant prognostic factor. CONCLUSIONS AND CLINICAL IMPORTANCE: Thromboelastometric parameters were altered in dogs with both hypercoagulable and hypocoagulable profiles. A hypocoagulable profile was significantly correlated with hemorrhagic diathesis and higher mortality rate.

Differences between coagulation and cytokine profiles in dogs of different ages.

In human medicine, age is a risk factor for thromboembolic diseases associated with hypercoagulable and antifibrinolytic states, but information in veterinary medicine is limited. This study compared the thromboelastometric (TEM) profiles of two groups of dogs of distinct ages. Ten healthy old (>10 years) Beagles and 10 healthy young (<3 years) Beagles were recruited. White blood cell counts and haematocrit were significantly lower in the old group compared to the young group, and fibrinogen, total proteins, globulins and monocyte chemoattractant protein-1 plasma concentrations were significantly higher in the old group. Comparisons of the TEM profiles indicated a hypercoagulable profile and a decrease in fibrinolytic activity in all old Beagles. The findings support the need to consider age as a possible risk factor for thrombosis in dogs.

A case of type B botulism in a pregnant bitch.

A two-year-old pregnant Gordon setter presented with acute onset of flaccid tetraparesis and respiratory distress. Neurological examination revealed diffuse lower motor neuron dysfunction. Clostridium botulinum neurotoxin B was isolated from the dog's serum. The dog was hospitalised and received supportive care; respiratory function was monitored but positive-pressure ventilation was not required. Recovery was complete within 1 month and parturition occurred without complication 49 days after admission. The puppies delivered lacked any obvious congenital defects and development during the first few months of life was normal. The source of contamination was suspected to be poorly conserved dry food. To the authors' knowledge, this is the first report of C. botulinum neurotoxin B isolation in a dog and the first report of botulism in a pregnant bitch.

HGF/SF is present in normal adult skeletal muscle and is capable of activating satellite cells.

We have shown that hepatocyte growth factor/scatter factor can stimulate activation and early division of adult satellite cells in culture, and that the action of hepatocyte growth factor/scatter factor is similar to the action of the unidentified satellite cell activator found in extracts of crushed muscle. We now provide new evidence that hepatocyte growth factor/scatter factor is present in uninjured adult rat skeletal muscle and that the activating factor in crushed muscle extract is hepatocyte growth factor/scatter factor. Immunoblots of crushed muscle extract demonstrate the presence of hepatocyte growth factor/scatter factor. Furthermore, crushed muscle extract stimulates the scattering of cultured MDCK cells. Immunolocalization studies with adult rat skeletal muscle show the presence of hepatocyte growth factor/scatter factor in the extracellular matrix surrounding muscle fibers; in addition, the receptor for hepatocyte growth factor/scatter factor, c-met, is localized to putative satellite cells. In muscle from mdx mice, hepatocyte growth factor/scatter factor and c-met are colocalized in activated satellite cells in regions of muscle repair. Moreover, the satellite cell-activating activity of crushed muscle extract is abolished by preincubation with anti-hepatocyte growth factor antibodies. Finally, direct injection of hepatocyte growth factor/scatter factor into uninjured tibialis anterior muscle of 12-month-old rats stimulated satellite cell activation. These experiments demonstrate that hepatocyte growth factor/scatter factor is present in muscle, can be released upon injury, and has the ability to activate quiescent satellite cells in vivo.