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1.
BMC Med Res Methodol ; 20(1): 24, 2020 02 07.
Article in English | MEDLINE | ID: mdl-32028898

ABSTRACT

BACKGROUND: Personalized healthcare promises to successfully advance the treatment of heterogeneous neurological disorders such as relapsing remitting multiple sclerosis by addressing the caveats of traditional healthcare. This study presents a framework for personalized prediction of treatment response based on real-world data from the NeuroTransData network. METHODS: A framework for personalized prediction of response to various treatments currently available for relapsing remitting multiple sclerosis patients was proposed. Two indicators of therapy effectiveness were used: number of relapses, and confirmed disability progression. The following steps were performed: (1) Data preprocessing and selection of predictors according to quality and inclusion criteria; (2) Implementation of hierarchical Bayesian generalized linear models for estimating treatment response; (3) Validation of the resulting predictive models based on several performance measures and routines, together with additional analyses that focus on evaluating the usability in clinical practice, such as comparing predicted treatment response with the empirically observed course of multiple sclerosis for different adherence profiles. RESULTS: The results revealed that the predictive models provide robust and accurate predictions and generalize to new patients and clinical sites. Three different out-of-sample validation schemes (10-fold cross-validation, leave-one-site-out cross-validation, and excluding a test set) were employed to assess generalizability based on three different statistical performance measures (mean squared error, Harrell's concordance statistic, and negative log-likelihood). Sensitivity to different choices of the priors, to the characteristics of the underlying patient population, and to the sample size, was assessed. Finally, it was shown that model predictions are clinically meaningful. CONCLUSIONS: Applying personalized predictive models in relapsing remitting multiple sclerosis patients is still new territory that is rapidly evolving and has many challenges. The proposed framework addresses the following challenges: robustness and accuracy of the predictions, generalizability to new patients and clinical sites and comparability of the predicted effectiveness of different therapies. The methodological and clinical soundness of the results builds the basis for a future support of patients and doctors when the current treatment is not generating the desired effect and they are considering a therapy switch. (A) The framework is developed using quality-proven real-world data of patients with relapsing remitting multiple sclerosis. Patients have heterogeneous individual characteristics and diverse disease profiles, indicated for example by variations in frequency of relapses and degree of disability. Longitudinal characteristics regarding disease history (e.g. number of previous relapses in the last 12 months) are extracted at the time of an intended therapy switch, i.e. at time point "Today" (left). All clinical parameters are captured in a standardized way (right). (B) The model predicts the course of the disease based on the observed data (panel A), and is able to account for the impact of various available therapies on chosen clinical endpoints. The resulting ranking of therapies has a dependency on patient characteristics, illustrated here by a different highest ranked therapy depending on the number of relapse in the previous 12 months. (C) The model is evaluated for various generalization properties. Compared to performance on the training set (gray) it is able to predict for new patients not part of the training set (red).Top: Prediction for new patients. Middle: Prediction for new clinical sites. Bottom: Prediction for different time windows. (D) In order to assess the clinical impact of the model, disease activity is compared between patients treated with the highest ranked therapy and those treated with any of the other therapies. Patients adhering to the highest ranked therapy are associated with a better disease outcome when compared to those who did not.


Subject(s)
Algorithms , Models, Theoretical , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Precision Medicine/methods , Bayes Theorem , Dimethyl Fumarate/therapeutic use , Disease Progression , Female , Fingolimod Hydrochloride/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Male , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Precision Medicine/statistics & numerical data , Prognosis , Recurrence , Treatment Adherence and Compliance/statistics & numerical data
2.
J Hum Genet ; 63(6): 707-716, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29618761

ABSTRACT

Seven subunits of the mitochondrial contact site and cristae junction (CJ) organizing system (MICOS) in humans have been recently described in function and structure. QIL1 (also named MIC13) is a small complex that is crucial for the maintenance and assembling of MICOS. A novel mutation of an essential splice site in the C19orf70 gene encoding QIL1 induces severe mitochondrial encephalopathy, hepatopathy and lactate acidosis consistent with psychomotor retardation. In addition, bilateral kidney stones were observed. Disassembly of MICOS complex subunits displays lack of MIC10-MIC26-MIC27-QIL1 subcomplex, resulting in aberrant cristae structure and a loss of cristae junctions and contact sites. In liver and muscle tissue, the activity of the respiratory chain complexes (OXPHOS) was severely impaired. Defects in MICOS complex do not only affect mitochondrial architecture, but also mitochondrial fusion, metabolic signalling, lipid trafficking and cellular electric homeostasis.


Subject(s)
Genes, Lethal , Liver Diseases/genetics , Membrane Proteins/genetics , Mitochondria/metabolism , Mitochondrial Encephalomyopathies/genetics , Mitochondrial Proteins/genetics , Mutation , Psychomotor Performance , Acidosis, Lactic/complications , Brain/diagnostic imaging , Electron Transport , Fatal Outcome , Female , Humans , Infant , Infant, Newborn , Kidney Calculi/complications , Liver/metabolism , Liver Diseases/complications , Liver Diseases/physiopathology , Magnetic Resonance Imaging , Mitochondrial Encephalomyopathies/complications , Mitochondrial Encephalomyopathies/diagnostic imaging , Mitochondrial Encephalomyopathies/physiopathology , Muscles/metabolism , Open Reading Frames , Oxidative Phosphorylation , RNA Splice Sites
3.
Animal ; 12(12): 2505-2510, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29510772

ABSTRACT

Exercise and physical training are known to affect gastrointestinal function and digestibility in horses and can lead to inaccurate estimates of nutrient and energy digestibility when markers are used. The effect of exercise on apparent nutrient digestibility and faecal recoveries of ADL and TiO2 was studied in six Welsh pony geldings subjected to either a low- (LI) or high-intensity (HI) exercise regime according to a cross-over design. Ponies performing LI exercise were walked once per day for 45 min in a horse walker (5 km/h) for 47 consecutive days. Ponies submitted to HI exercise were gradually trained for the same 47 days according a standardized protocol. Throughout the experiment, the ponies received a fixed level of feed and the daily rations consisted of 4.7 kg DM of grass hay and 0.95 kg DM of concentrate. The diet was supplemented with minerals, vitamins and TiO2 (3.0 g Ti/day). Total tract digestibility of DM, organic matter (OM), CP, crude fat, NDF, ADF, starch, sugar and energy was determined with the total faeces collection (TFC) method. In addition, DM and OM digestibility was estimated using internal ADL and the externally supplemented Ti as markers. Urine was collected on the final 2 days of each experimental period. Exercise did not affect apparent digestibility of CP, crude fat, starch and sugar. Digestibility of DM (DMD), OM (OMD), ADF and NDF tended to be lower and DE was decreased when ponies received the HI exercise regime. For all treatments combined, mean faecal recoveries of ADL and Ti were 87.8±1.7% and 99.3±1.7%, respectively. Ti was not detected in the urine, indicating that intestinal integrity was maintained with exercise. Dry matter digestibility estimated with the TFC, ADL and Ti for ponies subjected to LI exercise were 66.3%, 60.3% and 64.8%, respectively, while DMD for HI ponies were 64.2%, 60.3% and 65.2%, respectively. In conclusion, physical exercise has an influence on the GE digestibility of the feed in ponies provided with equivalent levels of feed intake. In addition, the two markers used for estimating apparent DMD and OMD indicate that externally supplemented Ti is a suitable marker to determine digestibility of nutrients in horses performing exercise unlike dietary ADL.


Subject(s)
Dietary Supplements , Horses/physiology , Lignin/analysis , Physical Conditioning, Animal , Titanium/analysis , Animal Feed/analysis , Animal Welfare , Animals , Biomarkers/analysis , Biomarkers/metabolism , Cross-Over Studies , Diet/veterinary , Dietary Fiber , Digestion , Feces/chemistry , Gastrointestinal Tract/metabolism , Lignin/metabolism , Male , Nutrients/metabolism , Titanium/metabolism
4.
Neth Heart J ; 26(4): 203-209, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29497946

ABSTRACT

AIM: Transthoracic contrast echocardiography (TTCE) is recommended for screening of pulmonary arteriovenous malformations (PAVMs) in hereditary haemorrhagic telangiectasia. Shunt quantification is used to find treatable PAVMs. So far, there has been no study investigating the reproducibility of this diagnostic test. Therefore, this study aimed to describe inter-observer and inter-injection variability of TTCE. METHODS: We conducted a prospective single centre study. We included all consecutive persons screened for presence of PAVMs in association with hereditary haemorrhagic telangiectasia in 2015. The videos of two contrast injections per patient were divided and reviewed by two cardiologists blinded for patient data. Pulmonary right-to-left shunts were graded using a three-grade scale. Inter-observer and inter-injection agreement was calculated with κ statistics for the presence and grade of pulmonary right-to-left shunts. RESULTS: We included 107 persons (accounting for 214 injections) (49.5% male, mean age 45.0 ± 16.6 years). A pulmonary right-to-left shunt was present in 136 (63.6%) and 131 (61.2%) injections for observer 1 and 2, respectively. Inter-injection agreement for the presence of pulmonary right-to-left shunts was 0.96 (95% confidence interval (CI) 0.9-1.0) and 0.98 (95% CI 0.94-1.00) for observer 1 and 2, respectively. Inter-injection agreement for pulmonary right-to-left shunt grade was 0.96 (95% CI 0.93-0.99) and 0.95 (95% CI 0.92-0.98) respectively. There was disagreement in right-to-left shunt grade between the contrast injections in 11 patients (10.3%). Inter-observer variability for presence and grade of the pulmonary right-to-left shunt was 0.95 (95% CI 0.91-0.99) and 0.97 (95% CI 0.95-0.99) respectively. CONCLUSION: TTCE has an excellent inter-injection and inter-observer agreement for both the presence and grade of pulmonary right-to-left shunts.

5.
Int J Cardiol ; 245: 114-118, 2017 Oct 15.
Article in English | MEDLINE | ID: mdl-28874282

ABSTRACT

BACKGROUND: Mutations in the genes ENG, ACVRL1 and SMAD4 that are part of the transforming growth factor-beta signalling pathway cause hereditary haemorrhagic telangiectasia (HHT). Mutations in non-HHT genes within this same pathway have been found to associate with aortic dilation. Therefore, we investigated the presence of aortic dilation in a large cohort of HHT patients as compared to non-HHT controls. METHODS: Chest computed tomography of consecutive HHT patients (ENG, ACVRL1 and SMAD4 mutation carriers) and non-HHT controls were reviewed. Aortic root dilation was defined as a z-score>1.96. Ascending and descending aorta dimensions were corrected for age, gender and body surface area. RESULTS: In total 178 subjects (57.3% female, mean age 43.9±14.9years) were included (32 SMAD4, 47 ENG, 50 ACVRL1 mutation carriers and 49 non-HHT controls). Aortopathy was present in a total of 42 subjects (24% of total). Aortic root dilatation was found in 31% of SMAD4, 2% of ENG, 6% of ACVRL1 mutation carriers, and 4% in non-HHT controls (p<0.001). The aortic root diameter was 36.3±5.2mm in SMAD4 versus 32.7±3.9mm in the non-SMAD4 group (p=0.001). SMAD4 was an independent predictor for increased aortic root (ß-coefficient 3.5, p<0.001) and ascending aorta diameter (ß-coefficient 1.6, p=0.04). CONCLUSIONS: SMAD4 gene mutation in HHT patients is independently associated with a higher risk of aortic root and ascending aortic dilation as compared to other HHT patients and non-HHT controls.


Subject(s)
Aortic Diseases/diagnostic imaging , Aortic Diseases/genetics , Mutation/genetics , Smad4 Protein/genetics , Telangiectasia, Hereditary Hemorrhagic/diagnostic imaging , Telangiectasia, Hereditary Hemorrhagic/genetics , Adult , Aorta/diagnostic imaging , Aortic Diseases/epidemiology , Dilatation , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Telangiectasia, Hereditary Hemorrhagic/epidemiology
6.
Orphanet J Rare Dis ; 11: 46, 2016 Apr 22.
Article in English | MEDLINE | ID: mdl-27102204

ABSTRACT

BACKGROUND: Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant disease associated with epistaxis, arteriovenous malformations and telangiectasias. Disease complications may result in premature death. METHOD: We investigated life-expectancies of parents of HHT patients compared with their non-HHT partners using self- or telephone-administered questionnaires sent to their children. Patients were extracted from the databases of 2 participating HHT Centres: the Toronto HHT Database (Toronto, Canada) and the St. Antonius Hospital HHT Database (Nieuwegein, The Netherlands). RESULTS: Two hundred twenty five/407 (55%) of respondents were included creating HHT- (n = 225) and control groups (n = 225) of equal size. Two hundred thirteen/225 (95%) of the HHT group had not been screened for organ involvement of the disease prior to death. The life expectancy in parents with HHT was slightly lower compared to parents without (median age at death 73.3 years in patients versus 76.6 years in controls, p0.018). Parents with ACVRL 1 mutations had normal life expectancies, whereas parents with Endoglin mutations died 7.1 years earlier than controls (p = 0.024). Women with Endoglin mutations lived a median of 9.3 years shorter than those without (p = 0.04). Seven/123 (5%) of deaths were HHT related with a median age at death of 61.5 years (IQ range 54.4-67.7 years). CONCLUSION: Our study showed that the life expectancy of largely unscreened HHT patients was lower than people without HHT. Female patients with Endoglin mutations were most strikingly at risk of premature death from complications. These results emphasize the importance of referring patients with HHT for screening of organ involvement and timely intervention to prevent complications.


Subject(s)
Life Expectancy , Telangiectasia, Hereditary Hemorrhagic/mortality , Activin Receptors, Type II/genetics , Aged , Antigens, CD/genetics , Endoglin , Female , Humans , Male , Mutation/genetics , Receptors, Cell Surface/genetics , Telangiectasia, Hereditary Hemorrhagic/genetics , Telangiectasia, Hereditary Hemorrhagic/physiopathology , Vascular Diseases/genetics , Vascular Diseases/mortality , Vascular Diseases/physiopathology
7.
J Vet Intern Med ; 30(3): 880-4, 2016 May.
Article in English | MEDLINE | ID: mdl-26995161

ABSTRACT

BACKGROUND: Atypical myopathy (AM) in horses is caused by the plant toxin hypoglycin A, which in Europe typically is found in the sycamore maple tree (Acer pseudoplatanus). Owners are concerned about whether their horses are in danger if they graze near maple trees. HYPOTHESIS/OBJECTIVES: To measure hypoglycin A in the most common maple tree species in the Netherlands, and to determine whether concentration of toxin is a predictor of AM in horses. METHODS: A total of 278 samples of maple tree leaves, sprouts, and seeds were classified by species. Mean concentrations of hypoglycin A were compared for the type of sample, the season and the occurrence of AM in the pasture (non-AM versus AM). Statistical analysis was performed using generalized a linear model (SPPS22). RESULTS: Almost all Acer pseudoplatanus samples contained hypoglycin A, with concentrations differing significantly among sources (P < .001). Concentrations were significantly higher in seeds from the AM group than in seeds from the non-AM group (856 ± 677 and 456 ± 358 mg/kg, respectively; P = .039). In sprouts and leaves this was not the case. Acer platanoides and Acer campestre samples did not contain detectable concentrations of hypoglycin A. CONCLUSIONS AND CLINICAL IMPORTANCE: Acer platanoides and campestre seem to be safe around paddocks and pastures, whereas almost all Acer pseudoplatanus samples contained hypoglycin A. In all AM cases, Acer pseudoplatanus was found. Despite significantly higher concentration of hypoglycin A in seeds of pastures where AM has occurred, individual prediction of AM cannot be made by measuring these concentrations because of the high standard deviation.


Subject(s)
Acer/chemistry , Horse Diseases/chemically induced , Hypoglycins/analysis , Muscular Diseases/veterinary , Plant Poisoning/veterinary , Seeds/chemistry , Animals , Horse Diseases/epidemiology , Horses , Hypoglycins/toxicity , Muscular Diseases/chemically induced , Muscular Diseases/epidemiology , Netherlands/epidemiology , Plant Leaves/chemistry
8.
Rhinology ; 53(4): 340-4, 2015 12.
Article in English | MEDLINE | ID: mdl-26735132

ABSTRACT

BACKGROUND: Patients with a hereditary vascular disorder called Rendu-Osler-Weber syndrome (Hereditary Haemorrhagic Telangiectasia, HHT) haemorrhage easily due to weak-walled vessels. Haemorrhage in lungs or brain can be fatal but patients suffer most from chronic and prolonged nosebleeds (epistaxis), the frequency and intensity of which increases with age. Several years ago, it was discovered serendipitously that the drug Thalidomide had beneficial effects on the disease symptoms in several of a small group of HHT patients: epistaxis and the incidence of anaemia were reduced and patients required fewer blood transfusions. In addition, they reported a better quality of life. However, Thalidomide has significant negative side effects, including neuropathy and fatigue. METHODS: We followed up all HHT patients in the Netherlands who had been taking Thalidomide at the time the original study was completed to find out (i) how many had continued taking Thalidomide and for how long (ii) the nature and severity of any side-effects and (iii) whether side-effects had influenced their decision to continue taking Thalidomide. RESULTS: Only a minority of patients had continued taking the drug despite its beneficial effects on their symptoms and that the side effects were the primary reason to stop. CONCLUSION: Despite symptom reduction, alternative treatments are still necessary for epistaxis in HHT patients and a large-scale clinical trial is not justified although incidental use in the most severely affected patients can be considered.


Subject(s)
Angiogenesis Inhibitors/adverse effects , Telangiectasia, Hereditary Hemorrhagic/drug therapy , Thalidomide/adverse effects , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Medication Adherence , Middle Aged , Treatment Outcome
9.
Vet Q ; 34(2): 85-91, 2014.
Article in English | MEDLINE | ID: mdl-24893614

ABSTRACT

BACKGROUND: Insulin resistance in horses is an emerging field of interest as it is thought to be a contributing factor in the pathogenesis of many equine conditions. OBJECTIVES: The objectives of the present study were to determine the effects of long-term oral administration of L-carnitine on insulin sensitivity, glucose disposal, plasma leptin concentrations and acylcarnitine spectrum both in plasma and urine. ANIMALS AND METHODS: Six 3-year-old healthy warmblood geldings were used. In a double blind 2 × 2 Latin square design at a dosage of 100 mg/kg body weight (BW)/day for 28 days the effects of oral supplementation of L-carnitine (as fumarate) were assessed. Glucose disposal and insulin sensitivity were measured by means of the euglycemic-hyperinsulinemic clamp technique. Radioimmunoassays were used to determine plasma leptin and insulin concentrations. Electrospray tandem mass spectrometry was used to assess acylcarnitines both in plasma and urine. Statistical analysis was performed using a linear mixed-effects model and P values <0.05 were considered significant. RESULTS: Long-term L-carnitine administration did not affect insulin sensitivity. Plasma leptin and free carnitine concentrations in plasma and urine increased significantly (P = 0.047 and 0.000, respectively) following L-carnitine administration as well as short-chain acylcarnitines in plasma and urinary excretion of short- and medium-chain acylcarnitines. CONCLUSION AND CLINICAL RELEVANCE: Given the effects of oral administration of L-carnitine further clinical study is necessary in order to assess the potential beneficial effects in equine patients suffering from metabolic myopathies such as acquired multiple acyl-CoA dehydrogenase deficiency. IMPACT FOR HUMAN MEDICINE: The current study supports the treatment rationale of short-chain acyl-CoA dehydrogenase deficiency in humans with L-carnitine at an oral dosage of 100 mg/kg BW/day.


Subject(s)
Carnitine/analogs & derivatives , Carnitine/administration & dosage , Insulin Resistance , Leptin/blood , Vitamin B Complex/administration & dosage , Animals , Carnitine/blood , Carnitine/urine , Glucose Clamp Technique/veterinary , Horses/blood , Horses/urine , Male , Plasma , Radioimmunoassay/veterinary
10.
Tijdschr Diergeneeskd ; 137(8): 514-21, 2012 Aug 01.
Article in English | MEDLINE | ID: mdl-22930982

ABSTRACT

This article reviews the literature on equine atypical myopathy (AM), an acute, severe rhabdomyolysis that occurs in horses at pasture. The prevalence, mortality, clinical signs, pathology, potential aetiology, typical aspects, diagnosis, treatment, and prognosis are described. Horse management, characteristic weather conditions, and possible preventive measures are also discussed. In addition, the characteristics of 54 highly probable or confirmed cases of equine AM occurring between autumn 2009 (27 cases) and spring 2010 (27 cases) in the Netherlands are described. Of the 54 affected horses, nineteen were mares, eleven geldings, and eight stallions; the sex of the other sixteen horses was not recorded. The mortality rate (74.5%) was in the same range as that reported in earlier studies. Many cases were reported at about the same time. Thirty-five horses had been pastured near maple trees, and in fifteen cases the maple trees were known to be infected with the fungus Rhytisma acerinum.


Subject(s)
Animal Husbandry/methods , Disease Outbreaks/veterinary , Horse Diseases/epidemiology , Muscular Diseases/veterinary , Rhabdomyolysis/veterinary , Animals , Female , Horse Diseases/diagnosis , Horse Diseases/prevention & control , Horses , Male , Muscular Diseases/diagnosis , Muscular Diseases/epidemiology , Muscular Diseases/prevention & control , Netherlands/epidemiology , Rhabdomyolysis/diagnosis , Rhabdomyolysis/epidemiology , Rhabdomyolysis/prevention & control , Seasons
11.
Equine Vet J ; 44(5): 614-20, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22448904

ABSTRACT

REASONS FOR PERFORMING STUDY: Improved understanding of the epidemiology of atypical myopathy (AM) will help to define the environmental factors that permit or support the causal agent(s) to exert toxicity. OBJECTIVES: This European survey of AM aimed to describe spatiotemporal distribution, survival, clinical signs, circumstances in which AM develops and its different expressions between countries and over time. METHODS: The spatiotemporal distribution, history and clinical features of AM cases reported to the Atypical Myopathy Alert Group from 2006 to 2009 were described. Comparisons of data from the most severely affected countries and from the large outbreaks were made with Fisher's exact and Welch's tests with Bonferroni correction. RESULTS: Of 600 suspected cases, 354 met the diagnostic criteria for confirmed or highly probable AM. The largest outbreaks occurred during the autumns of 2006 and 2009 in Belgium, France and Germany. For the first time, donkeys, zebras and old horses were affected, and clinical signs such as gastrointestinal impaction, diarrhoea, penile prolapse, buccal ulceration and renal dysfunction were observed. Affected horses spent >6 h/day on pastures that almost always contained or were surrounded by trees. The latency period was estimated at up to 4 days. Overall survival rate was 26%. Although differences between countries in affected breeds, body condition, horse management and pasture characteristics were recognised, the common presenting clinical signs and mortality were similar between countries. CONCLUSIONS AND POTENTIAL RELEVANCE: This study describes new data on case details, history and clinical course of AM that is of preventive, diagnostic and therapeutic value. However, the true impact of the findings of this study on the development of or severity of AM should be tested with case-control studies.


Subject(s)
Disease Outbreaks/veterinary , Equidae , Muscular Diseases/veterinary , Animal Husbandry , Animals , Environment , Europe/epidemiology , Muscular Diseases/epidemiology , Muscular Diseases/pathology , Time Factors
12.
Equine Vet J ; 44(5): 621-5, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22413891

ABSTRACT

REASONS FOR PERFORMING STUDY: Appropriate management of atypical myopathy (AM) requires the establishment of an accurate diagnosis and prognosis. Furthermore, preventive measures to avoid AM need to be refined. OBJECTIVES: The aims of the study were as follows: 1) to improve the diagnosis of AM; 2) to identify prognostic predictors; and 3) to refine recommended preventive measures based on indicators of risk factors. METHODS: An exploratory analysis of cases in Europe between 2006 and 2009 reported to the Atypical Myopathy Alert Group was conducted. Based on clinical data, reported cases were allocated into 2 groups: confirmed or highly probable AM (AM group; further divided into survivors and nonsurvivors); and cases with a low probability of having AM or with another final diagnosis (non-AM group). Using Welch's test and odds ratios corrected for multiple comparisons, the AM vs. non-AM groups were compared to identify indicators for diagnosis and risk factors, and survivors vs. nonsurvivors in the AM group were compared to identify prognostic factors. Sensitivity, specificity and positive and negative predictive values were calculated for specific clinical signs related to final diagnosis and outcome. RESULTS: From 600 reported cases, 354 AM cases (survival rate of 26%) and 69 non-AM cases were identified, while there were insufficient data to categorise the remainder. Variables valuable for diagnosing AM compared with similar diseases were as follows: presence of dead leaves and wood and/or trees on pastures; sloping pastures; full-time pasture access; no food supplementation; normal body condition; pigmenturia; normothermia; and congested mucous membranes. Nonsurvival was associated with recumbency, sweating, anorexia, dyspnoea, tachypnoea and/or tachycardia. Survival was associated with remaining standing most of the time, normothermia, normal mucous membranes, defaecation and vitamin and antioxidant therapy. CONCLUSIONS AND POTENTIAL RELEVANCE: This study refines the list of risk factors for AM. Clinical signs valuable for diagnosis and prognosis have been identified, enabling clinicians to improve management of AM cases.


Subject(s)
Disease Outbreaks/veterinary , Horse Diseases/etiology , Muscular Diseases/veterinary , Animals , Case-Control Studies , Europe/epidemiology , Horse Diseases/epidemiology , Horses , Models, Biological , Muscular Diseases/diagnosis , Muscular Diseases/epidemiology , Muscular Diseases/etiology , Risk Factors , Time Factors
13.
Article in German | MEDLINE | ID: mdl-22290165

ABSTRACT

Provision of inpatient elderly care is characterized by factors that favor the onset of burnout, with psychosomatic complaints, a drop in performance, periods of absence due to sickness, and early retirement from the sector regularly being observed in this respect. This study summarizes the research of the past 11 years, regarding the prevalence of burnout among inpatient elderly care employees. A total of 24 studies were identified during a systematic database search conducted in May 2011. As the studies conceptualize burnout differently and are based on different survey tools, it is not possible to draw a clear conclusion regarding its prevalence. There is empirical evidence of a correlation between burnout and the care staff/patient ratio, workloads, the freedom to make decisions, job satisfaction, and neuroticism. There is no confirmation of a correlation between burnout and marital status, income, or shift work. There are contradictory findings regarding the correlation between burnout and sociodemographic aspects (e.g., age and gender) as well as burnout and the type of care institution, working hours, and violence perpetrated by patients.


Subject(s)
Burnout, Professional/epidemiology , Health Services for the Aged/statistics & numerical data , Medical Staff/statistics & numerical data , Occupational Diseases/epidemiology , Adult , Female , Germany/epidemiology , Humans , Male , Middle Aged , Prevalence , Workforce , Young Adult
14.
Mol Genet Metab ; 104(3): 273-8, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21843962

ABSTRACT

Earlier research on ten horses suffering from the frequently fatal disorder atypical myopathy showed that MADD (multiple acyl-CoA dehydrogenase deficiency) is the biochemical derangement behind atypical myopathy. From five horses that died as a result of this disease and seven healthy control horses, urine and plasma were collected ante mortem and muscle biopsies were obtained immediately post-mortem (2 patients and 7 control horses), to analyse creatine, purine and carbohydrate metabolism as well as oxidative phosphorylation. In patients, the mean creatine concentration in urine was increased 17-fold and the concentration of uric acid approximately 4-fold, compared to controls. The highest degree of depletion of glycogen was observed in the patient with the most severe myopathy clinically. In this patient, glycolysis was more active than in the other patients and controls, which may explain this depletion. One patient demonstrated very low phosphoglycerate mutase (PGAM) activity, less than 10% of reference values. Most respiratory chain complex activity in patients was 20-30% lower than in control horses, complex II activity was 42% lower than normal, and one patient had severely decrease ATP-synthase activity, more than 60% lower than in control horses. General markers for myopathic damage are creatine kinase (CK) and lactic acid in plasma, and creatine and uric acid in urine. To obtain more information about the cause of the myopathy analysis of carbohydrate, lipid and protein metabolism as well as oxidative phosphorylation is advised. This study expands the diagnostic possibilities of equine myopathies.


Subject(s)
Creatine , Horse Diseases/metabolism , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/complications , Oxidative Phosphorylation , Phosphoglycerate Mutase/deficiency , Physical Conditioning, Animal , Rhabdomyolysis/metabolism , Animals , Aspartate Aminotransferases/blood , Base Sequence , Creatine/urine , Creatine Kinase/blood , DNA Primers/genetics , Female , Horses , L-Lactate Dehydrogenase/blood , Malonates/urine , Mitochondrial Proton-Translocating ATPases/metabolism , Molecular Sequence Data , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/blood , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/urine , Phosphoglycerate Mutase/genetics , Rhabdomyolysis/etiology , Sequence Analysis, DNA , Succinates/urine , Uric Acid/urine
15.
Res Vet Sci ; 91(1): 144-149, 2011 Aug.
Article in English | MEDLINE | ID: mdl-20863542

ABSTRACT

The objective of this study is to assess the influence of acute exercise, training and intensified training on the plasma amino acid profile. In a 32-week longitudinal study using 10 Standardbred horses, training was divided into four phases, including a phase of intensified training for five horses. At the end of each phase, a standardized exercise test, SET, was performed. Plasma amino acid concentrations before and after each SET were measured. Training significantly reduced mean plasma aspartic acid concentration, whereas exercise significantly increased the plasma concentrations of alanine, taurine, methionine, leucine, tyrosine and phenylalanine and reduced the plasma concentrations of glycine, ornithine, glutamine, citrulline and serine. Normally and intensified trained horses differed not significantly. It is concluded that amino acids should not be regarded as limiting training performance in Standardbreds except for aspartic acid which is the most likely candidate for supplementation.


Subject(s)
Amino Acids/blood , Horses/blood , Physical Conditioning, Animal/physiology , Animals , Horses/physiology , Longitudinal Studies , Male
16.
J Med Genet ; 48(2): 73-87, 2011 Feb.
Article in English | MEDLINE | ID: mdl-19553198

ABSTRACT

BACKGROUND: HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. OBJECTIVE: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. METHODS: The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. RESULTS: The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.


Subject(s)
Activin Receptors, Type II/genetics , Antigens, CD/genetics , Epistaxis/therapy , Gastrointestinal Hemorrhage/pathology , Receptors, Cell Surface/genetics , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Vascular Malformations/pathology , Adult , Child , Early Detection of Cancer , Endoglin , Epistaxis/pathology , Genetic Testing , Humans , Magnetic Resonance Imaging , Mutation/genetics , Smad4 Protein/genetics , Telangiectasia, Hereditary Hemorrhagic/genetics , Telangiectasia, Hereditary Hemorrhagic/pathology
18.
Equine Vet J Suppl ; (38): 147-51, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21058997

ABSTRACT

REASONS FOR PERFORMING STUDY: The quantity of glucose disposal during exercise (walk and trot) compared to rest by use of the hyperglycaemic clamp technique has not been reported previously and has relevance to nutritional requirements. HYPOTHESIS: Exercise (walk and trot) significantly increases glucose disposal compared to rest. METHODS: Seven healthy Dutch Warmblood mares, all in dioestrus, mean ± s.d. age 11.6 ± 2.4 years and weighing 569 ± 40 kg were fasted for 12 h prior to a hyperglycaemic clamp at rest (maintaining a steady state of the blood glucose concentration during 30 min), walk (10 min, 1.5 m/s), trot (20 min, 4.4 m/s), walk (10 min, 1.5 m/s) and rest again (maintaining a steady state during 30 min). Plasma glucose concentrations were measured every 5 min. The mean rate of glucose disposal was calculated by corrections for glucose loss via the glucose space and urine. A one-way ANOVA with post hoc Bonferroni was performed. RESULTS: The mean ± s.d. rate of glucose disposal was 15.0 ± 2.1 at first rest, 25.1 ± 6.2 at first walk, 37.4 ± 9.1 at trot, 33.0 ± 13.1 at second walk and 18.7 ± 4.6 µmol/kg bwt/min at second rest. Values at trot and at second walk differed significantly from values at first rest, whereas values at both rests were similar as well as at first rest and at first walk. CONCLUSIONS: Mean rate of glucose disposal of Warmblood horses increased 2.5 times during trot compared to basal. POTENTIAL RELEVANCE: The hyperglycaemic clamp technique is an attractive nonisotope method to assess the rate of glucose disposal in exercising horses.


Subject(s)
Blood Glucose/metabolism , Glucose Clamp Technique/veterinary , Horses/blood , Horses/metabolism , Physical Conditioning, Animal/physiology , Animals , Female , Horses/genetics
20.
Mol Genet Metab ; 101(2-3): 289-91, 2010.
Article in English | MEDLINE | ID: mdl-20655779

ABSTRACT

This case-series describes fourteen horses suspected of equine acquired multiple acyl-CoA dehydrogenase deficiency (MADD) also known as atypical myopathy of which seven cases were confirmed biochemically with all horses having had access to leaves of the Maple tree (Acer pseudoplatanus) covered with European tar spot (Rhytisma acerinum). Assessment of organic acids, glycine conjugates, and acylcarnitines in urine was regarded as gold standard in the biochemical diagnosis of equine acquired multiple acyl-CoA dehydrogenase deficiency.


Subject(s)
Acer , Foodborne Diseases/veterinary , Horse Diseases/enzymology , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/veterinary , Plant Leaves , Animals , Ascomycota , Carboxylic Acids/urine , Carnitine/analogs & derivatives , Carnitine/urine , Female , Glycine/urine , Horse Diseases/urine , Horses , Male , Plant Diseases/microbiology
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