A gait paradigm reveals different patterns of abnormal cerebellar motor learning in primary focal dystonias.

Accumulating evidence points to a role of the cerebellum in the pathophysiology of primary dystonia. The aim of this study was to investigate whether the abnormalities of cerebellar motor learning in primary dystonia are solely detectable in more pure forms of cerebellum-dependent associative motor learning paradigms, or whether these are also present in other motor learning paradigms that rely heavily on the cerebellum but in addition require a more widespread sensorimotor network. Twenty-six patients with various forms of focal dystonia and 10 age-matched healthy controls participated in a motor learning paradigm on a split-belt treadmill. By using reflective markers, three-dimensional kinematics were recorded using a 6-camera motion analysis system. Adaptation walking parameters were analyzed offline, comparing the different dystonia groups and healthy controls. Patients with blepharospasm and writer's cramp were significantly impaired on various adaptation walking parameters. Whereas results of cervical dystonia patients did not differ from healthy controls in terms of adaptation walking parameters, differences in parameters of normal gait were found. We have here demonstrated abnormal sensorimotor adaptation with the split-belt paradigm in patients with blepharospasm and writer's cramp. This reinforces the current concept of cerebellar dysfunction in primary dystonia, and that this extends beyond more pure forms of cerebellum-dependent associative motor learning paradigms. However, the finding of normal adaptation in cervical dystonia patients indicates that the pattern of cerebellar dysfunction may be slightly different for the various forms of primary focal dystonia, suggesting that actual cerebellar pathology may not be a primary driving force in dystonia.

Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia.

OBJECTIVE: Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older patients with early-onset and late-onset schizophrenia. METHODS: Theory of Mind abilities were assessed using the Hinting Task in 15 older patients (age 60 years and older) with early-onset paranoid schizophrenia, 15 older patients with late-onset paranoid schizophrenia and 30 healthy controls. ANCOVA was performed to test differences between groups. Analyses were adjusted for level of education. Effect sizes, partial eta squared (ε(2) ), were computed as an indication of the clinical relevance of the findings. RESULTS: Patients with early-onset schizophrenia scored significantly lower on the Hinting Task (mean 16.1; SD 4.3) compared with patients with late-onset schizophrenia (mean 18.6; SD 1.5) and with healthy controls (mean 19.0; SD 1.4). The effect size of this difference was large (ε(2) = 0.2). CONCLUSIONS: These results suggest that ToM functioning may be a protective factor modulating the age at onset of psychosis. Further studies into the relationship between social cognition and onset age of psychosis are warranted.

[Adjustment and alteration of the quality indicators in the Basic Set (GGZ) for use in child and adolescent psychiatry]. / Aanpassing en aanvulling van kwaliteitsindicatoren uit de basisset ggz voor gebruik in de kinder- en jeugdpsychiatrie.

BACKGROUND: Transparency by means of quality indicators is regarded as a method for monitoring and improving the quality of care. In the Dutch mental health service (GGZ) a generic basic set of indicators has been developed, but it is not clear whether the set is suitable for use in child and adolescent psychiatry. AIM: To assess whether the GGZ Basic Set of performance indicators for 2007-2008 was suitable for use in a child and adolescent psychiatric setting and to detect any omissions in that set. METHOD: A heterogeneous national group of eight health professionals and five 'stakeholders' in child and adolescent mental health judged the existing Basic Set by means of a Delphi procedure consisting of two written rounds and a panel discussion. The experts assessed potential indicators with regard to necessity, validity, clarity and applicability to child and adolescent psychiatry using a scale of 0 to 9. Indicators scoring more than 7 were considered to be appropriate. RESULTS: Only two of the 54 indicators were considered appropriate. A lower cut-off point would leave 16 indicators, of which 10 related to the outcome of treatment. One of the nine proposed innovative indicators was added. CONCLUSION: Very few of the indicators in the Basic Set were considered to be suitable for use in child and adolescent psychiatry. Respondents expressed a preference for a limited number of indicators that emphasised the opinion of the patient and of parents rather than the outcomes of treatment.

[Frontotemporal dementia and schizophrenia in later life: a comparison of executive and general cognitive functioning]. / Frontotemporale dementie en schizofrenie op oudere leeftijd: een verkenning van executief en globaal cognitief functioneren.

BACKGROUND: Frontotemporal dementia (FTD) is characterised clinically by progressive changes in behaviour and personality; these changes are followed by cognitive disorder. FTD needs to be differentiated from other forms of dementia and from psychiatric conditions such as schizophrenia. Both FTD and schizophrenia lead to cognitive disorders and particularly to executive impairments. AIM: To compare executive and general cognitive functioning in patients with FTD and in patients with schizophrenia in later life. METHOD: As cognitive screening instruments we used the 'Frontal Assessment Battery' (FAB) and the 'Mini-Mental State Examination' (MMSE). The FAB en MMSE test results (retrieved from the database of the Alzheimer centre of the VU medical centre) for 25 outpatients diagnosed as having FTD were compared with the test results (retrieved from the 'SOUL' study database) for 31 elderly schizophrenia patients. RESULTS: In both the fab and the MMSE tests the scores for the patients with FTD were significantly lower than the scores for the patients with schizophrenia. CONCLUSION: Our study suggests that, despite the clinical similarities, there are differences between patients with FTD and elderly patients with schizophrenia with regard to executive and general cognitive functioning. Further studies are needed in order to differentiate between the two illnesses.

Recommendations for studies on dynamic arm support devices in people with neuromuscular disorders: a scoping review with expert-based discussion.

PURPOSE: Neuromuscular disorders are characterised by muscle weakness that limits upper extremity mobility, but can be alleviated with dynamic arm support devices. Current research highlights the importance and difficulties of evidence-based recommendations for device development. We aim to provide research recommendations primarily concerning upper extremity body functions, and secondarily activity and participation, environmental and personal factors. METHODS: Evidence was synthesised from literature, ongoing studies, and expert opinions and tabulated within a framework based on a combination of the International Classification of Functioning, Disability and Health (ICF) model and contextual constructs. RESULTS: Current literature mostly investigated the motor capacity of muscle function, joint mobility, and upper body functionality, and a few studies also addressed the impact on activity and participation. In addition, experts considered knowledge on device utilisation in the daily environment and characterising the beneficiaries better as important. Knowledge gaps showed that ICF model components and contextual constructs should be better integrated and more actively included in future research. CONCLUSIONS: It is recommended to, first, integrate multiple ICF model components and contextual constructs within one study design. Second, include the influence of environmental and personal factors when developing and deploying a device. Third, include short-term and long-term measurements to monitor adaptations over time. Finally, include user satisfaction as guidance to evaluate the device effectiveness.IMPLICATIONS ON REHABILITATIONSynthesized evidence will support future research and development of dynamic arm supports.Tabulated evidence stresses the importance of integrating ICF model components and contextual constructs to fill the knowledge gaps.Presented knowledge gaps and proposed steps guide the set up of future studies on dynamic arm supports.

[Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial]. / Preventieve intraveneuze hydratie ter voorkoming van contrastnefropathie helpt niet.

BACKGROUND: Intravenous saline is recommended in clinical practice guidelines as the cornerstone for preventing contrast-induced nephropathy in patients with compromised renal function. However, clinical-effectiveness and cost-effectiveness of this prophylactic hydration treatment in protecting renal function has not been adequately studied in the population targeted by the guidelines, against a group receiving no prophylaxis. This was the aim of the AMACING trial. METHODS: AMACING is a prospective, randomised, phase 3, parallel-group, open-label, non-inferiority trial of patients at risk of contrast-induced nephropathy according to current guidelines. High-risk patients (with an estimated glomerular filtration rate [eGFR] of 30-59 mL per min/1·73 m²) aged 18 years and older, undergoing an elective procedure requiring iodinated contrast material administration at Maastricht University Medical Centre, the Netherlands, were randomly assigned (1:1) to receive intravenous 0·9% NaCl or no prophylaxis. We excluded patients with eGFR lower than 30 mL per min/1·73 m², previous dialysis, or no referral for intravenous hydration. Randomisation was stratified by predefined risk factors. The primary outcome was incidence of contrast-induced nephropathy, defined as an increase in serum creatinine from baseline of more than 25% or 44 µmol/L within 2-6 days of contrast exposure, and cost-effectiveness of no prophylaxis compared with intravenous hydration in the prevention of contrast-induced nephropathy. We measured serum creatinine immediately before, 2-6 days, and 26-35 days after contrast-material exposure. Laboratory personnel were masked to treatment allocation. Adverse events and use of resources were systematically recorded. The non-inferiority margin was set at 2·1%. Both intention-to-treat and per-protocol analyses were done. This trial is registered with ClinicalTrials.gov, number NCT02106234. FINDINGS: Between June 17, 2014, and July 17, 2016, 660 consecutive patients were randomly assigned to receive no prophylaxis (n=332) or intravenous hydration (n=328). 2-6 day serum creatinine was available for 307 (92%) of 332 patients in the no prophylaxis group and 296 (90%) of 328 patients in the intravenous hydration group. Contrast-induced nephropathy was recorded in eight (2·6%) of 307 non-hydrated patients and in eight (2·7%) of 296 hydrated patients. The absolute difference (no hydration vs hydration) was -0·10% (one-sided 95% CI -2·25 to 2·06; one-tailed p=0·4710). No hydration was cost-saving relative to hydration. No haemodialysis or related deaths occurred within 35 days. 18 (5·5%) of 328 patients had complications associated with intravenous hydration. INTERPRETATION: We found no prophylaxis to be non-inferior and cost-saving in preventing contrast-induced nephropathy compared with intravenous hydration according to current clinical practice guidelines.

Assessing impaired hypoglycemia awareness in type 1 diabetes: agreement of self-report but not of field study data with the autonomic symptom threshold during experimental hypoglycemia.

OBJECTIVE: The aim of our study was to determine the agreement of two noninvasive methods, a self-report and a field study method, for the assessment of impaired hypoglycemia awareness with a gold standard criterion of hypoglycemia awareness, the autonomic symptom threshold during experimental hypoglycemia. RESEARCH DESIGN AND METHODS: A total of 19 type 1 diabetic patients completed a standardized questionnaire to assess impaired hypoglycemia awareness and performed a hand-held computer (HHC) study to assess their recognition of hypoglycemic episodes occurring during 24 weeks. Patients subsequently underwent a stepped hypoglycemic clamp to study responses to standardized hypoglycemia. Diagnoses of impaired hypoglycemia awareness were based on the separate self-report questions, a composite self-report score, and three different cutoff levels for the percentage of accurately recognized hypoglycemic episodes during the field study Agreement of these noninvasive measures with the hypoglycemic clamp measure were tested by calculating kappa values, sensitivity, and specificity. RESULTS: The composite self-report score agreed reasonably well with the hypoglycemic clamp measure (kappa 0.49, sensitivity 66.7%, and specificity 85.7%) and showed a better agreement than the separate self-report questions. The HHC criterion of impaired hypoglycemia awareness did not agree with the hypoglycemic clamp criterion at any of the cutoff levels tested. CONCLUSIONS: The composite self-report tested in this study is a reasonably reliable assessment method for the diagnosis of impaired hypoglycemia awareness, using the physiological definition of an absence of autonomic symptoms at a blood glucose level of 3 mmol/l. In contrast, the recognition of hypoglycemic events in everyday life as measured using the HHC method is not related to the hypoglycemic clamp criterion.

Nighttime insulin kinetics and glycemic control in type 1 diabetes patients following administration of an intermediate-acting lispro preparation.

OBJECTIVE: To determine insulin kinetics and overnight glycemic control after bedtime administration of a new intermediate-acting insulin preparation called neutral protamine lispro (NPL). RESEARCH DESIGN AND METHODS: We studied 12 patients with well-controlled type 1 diabetes. The study had a double-blind, randomized, crossover design. After a lead-in period of 10-14 days two experiments were carried out with an interval of 2-7 days. During these experiments overnight insulin kinetics and fasting blood glucose levels were studied after evening administration of NPH insulin and NPL. Blood glucose levels < 3.8 mmol/l were treated by means of a variable infusion of a 20% glucose solution. RESULTS: A trend toward a shorter time to peak insulin concentration was observed after administration of NPL (P = 0.07). No differences between NPH and NPL were detected in the total area under the curve (AUC) for insulin, in insulin levels before breakfast, or in glucose levels before breakfast (P = 0.5, 0.6, and 0.4, respectively). CONCLUSIONS: We detected no major differences between NPH and NPL in the total AUC for insulin, prebreakfast glucose levels, or prebreakfast insulin levels. Therefore, we conclude that NPH and NPL are equally effective in controlling overnight glycemia.

Optimized basal-bolus therapy using a fixed mixture of 75% lispro and 25% NPL insulin in type 1 diabetes patients: no favorable effects on glycemic control, physiological responses to hypoglycemia, well-being, or treatment satisfaction.

OBJECTIVE: To investigate the effects of a multiple injection regimen with a mixture of 75% lispro and 25% intermediate-acting insulin (lispro high mixture [HM]) before meals on glycemic control, physiological responses to hypoglycemia, well-being, and treatment satisfaction. RESEARCH DESIGN AND METHODS: We studied 35 type 1 diabetes patients. After an 8- to 10-week lead-in period, patients were randomized to HM or human regular insulin therapy for 12-14 weeks. During the lead-in and treatment periods, HbA1c levels and hypoglycemic frequencies were measured, and patients completed the Well-Being Questionnaire and the Diabetes Treatment Satisfaction Questionnaire. In 19 patients, responses to hypoglycemia were tested during stepped euglycemic-hypoglycemic clamps. RESULTS: HM treatment improved postprandial glycemia but had no effect on HbA1c, frequency of hypoglycemia, well-being, or treatment satisfaction. During experimental hypoglycemia, HM therapy was associated with a slightly lower total adrenaline response and a higher autonomic symptom threshold (i.e., the autonomic symptom response occurred at a lower blood glucose level) than human regular insulin therapy. We speculate that this effect resulted from an accumulation of insulin during the night. CONCLUSIONS: Multiple injection therapy with HM rather than human regular insulin before meals does not offer advantages regarding glycemic control, frequency of hypoglycemia, well-being, or treatment satisfaction. In addition, this regimen causes an attenuation of the adrenaline and autonomic symptom responses to hypoglycemia.

Infectious agents associated with diarrhoea of calves in the canton of Tilarán, Costa Rica.

A case-control study of calves under 3 months of age was carried out by weekly visits to 15 farms in the canton of Tilarán, Costa Rica. Most farms were dedicated to beef or dual-purpose (DP) production. Faecal samples were collected over a 6-month period from a total of 194 calves with clinical signs and from 186 animals without clinical signs of diarrhoea as assessed by a scoring system. The samples were investigated for the presence of viruses, bacteria and parasites. Torovirus was detected for the first time in Costa Rica and was present in 14% of calves with diarrhoea and in 6% of the controls. Coronavirus and Rotavirus were less frequently encountered in either one of the groups (in 9 and 7% of scouring calves and in 1 and 2% of controls, respectively). Escherichia coli was detected in 94% of all the faecal samples, but isolates from only three samples from calves with diarrhoea contained the K99 antigen. Similarly, Salmonella was found only in scouring calves. Cryptosporidium oocysts were detected in animals with signs of diarrhoea, while other coccidia oocysts, Strongylida and Strongyloides eggs were frequently found in animals both with and without diarrhoea. A conditional logistic regression (CLR) analysis to compare healthy and scouring calves showed a significant difference with regard to the presence of Torovirus, Rotavirus and Coronavirus.

Three-dimensional ultrasonography of normal fetal lung volume: a preliminary study.

The objective of this preliminary study was to evaluate three-dimensional ultrasonographic lung volume measurement in the normally developing fetus in the second half of pregnancy. Total fetal lung volume was determined by subtraction of fetal heart volume from thoracic volume, using the perpendicular transverse, sagittal and frontal planes of the fetus. Technically acceptable lung volume measurements were obtained in 29 out of 34 women with an uncomplicated pregnancy. A statistically significant increase in normal fetal lung volume was established with advancing gestational age and with increasing fetal estimated weight, demonstrating an approximately seven-fold rise in fetal lung volume during the second half of pregnancy. Three-dimensional ultrasonography can be applied for estimation of fetal lung volume. Whether this technique is useful in the prenatal prediction of pulmonary hypoplasia remains to be determined.

Biological and behavioural determinants of the frequency of mild, biochemical hypoglycaemia in patients with Type 1 diabetes on multiple insulin injection therapy.

BACKGROUND: Severe hypoglycaemic episodes are an important source of morbidity in people with Type 1 diabetes. The occurrence of severe hypoglycaemia is strongly related to the frequency of low blood glucose readings. The aim of this exploratory study was to identify determinants of the frequency of mild, biochemical hypoglycaemia in patients with Type 1 diabetes treated with multiple insulin injection therapy. METHODS: We studied 31 patients with Type 1 diabetes in reasonable glycaemic control (HbA(1c)

Fetal liver volume measurement by three-dimensional ultrasonography: a preliminary study.

OBJECTIVE: To establish the application of three-dimensional ultrasonography in measuring fetal liver volume during the second half of normal pregnancy. DESIGN: A prospective cross-sectional study of normal fetal liver volume at 19-39 weeks of gestation (median 29 weeks). SUBJECTS: Thirty-four non-smoking women with a singleton pregnancy resulting in the delivery of a healthy infant with a birth weight between the 5th and 95th centiles according to the Kloosterman tables adjusted for maternal parity and fetal sex. METHODS: For fetal liver volume measurements, a simultaneous recording of a frontal section of the liver immediately anterior to the stomach and a sagittal section of the liver were obtained using a standard Combison 530 ultrasound machine with a 5-MHz annular array transducer for volume scanning. RESULTS: Technically acceptable fetal liver volume measurements were obtained in 25 of 34 participating women. Mean fetal liver volume data (P50) ranged between 8 ml at 20 weeks' gestation and 116 ml at 38 weeks' gestation. A statistically significant increase in normal fetal liver volume was found with advancing gestational age (p < 0.0001) and with increasing estimated fetal weight (p < 0.00001). CONCLUSIONS: Three-dimensional ultrasound allows measurement of fetal liver volume, and this demonstrated an approximately 14-fold increase during the second half of pregnancy. It is speculated that three-dimensional fetal liver volume measurement may identify the fetus at risk of growth restriction.

Substitution of night-time continuous subcutaneous insulin infusion therapy for bedtime NPH insulin in a multiple injection regimen improves counterregulatory hormonal responses and warning symptoms of hypoglycaemia in IDDM.

In patients with insulin-dependent diabetes mellitus (IDDM) good glycaemic control confers an enhanced risk of hypoglycaemia. Nocturnal hypoglycaemia occurs frequently and contributes to the syndrome of hypoglycaemia unawareness. In order to avoid nocturnal hypoglycaemia we substituted night-time continuous subcutaneous insulin infusion (CSII) therapy in 14 patients with well-controlled IDDM using a multiple injection regimen for the more variable bedtime NPH insulin. During a stepwise hypoglycaemic clamp we studied the effect of this regimen on counterregulatory hormonal responses, warning symptoms and cognitive function. In addition, we investigated the incidence of daytime hypoglycaemia and the acceptability of night-time CSII treatment. CSII was associated with a lower frequency of hypoglycaemia (mean+/-SEM): 16.1+/-3.1 vs 23.6+/-3.3) episodes during the last 6 weeks of treatment, p=0.03 (CSII vs NPH)) with maintenance of good glycaemic control (HbA1c 7.2+/-0.2 vs 7.1+/-0.2 %, p=0.2). Hypoglycaemic thresholds for the growth hormone response and for autonomic symptoms were lower for CSII treatment than for NPH treatment. Of 14 patients 6 decided to continue with the nocturnal CSII treatment. In conclusion, nocturnal CSII improves warning symptoms and counterregulatory hormonal responses to hypoglycaemia and is an acceptable treatment strategy for patients suffering from hypoglycaemia unawareness, as demonstrated in this acute feasibility study.