A language-based sum score for the course and therapeutic intervention in primary progressive aphasia.

BACKGROUND: With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions. METHODS: We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials. RESULTS: Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures. CONCLUSION: Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.

A randomized controlled comparison of seclusion and mechanical restraint in inpatient settings.

OBJECTIVE: No evidence is available on the relative restrictiveness of seclusion and mechanical restraint, although guidelines recommend use of the least restrictive intervention. This study compared the restrictiveness of these interventions from patients' point of view. METHODS: Data were collected from three general psychiatric admission units in South Germany. A total of 102 patients with schizophrenia, an affective disorder, or a personality disorder were included in a comprehensive cohort study with optional randomization. Restrictions of human rights as measured by the Coercion Experience Scale (CES) were the primary outcome variable. Possible total scores range from 1 to 5, with higher scores indicating a higher level of restriction. RESULTS: Twenty-six patients were randomly assigned to seclusion (N=12) or mechanical restraint (N=14). A total of 76 were excluded from randomization and included in the cohort arms (48 experienced seclusion, and 28 experienced mechanical restraint). No difference in mean CES total scores was found between the randomly assigned patients after they experienced seclusion or mechanical restraint (seclusion median score=1.88 [range 1.24-4.24]; restraint median score=2.14 [range 1.28-4.00]). When randomly assigned patients and patients in the cohort arms were considered as a group, no significant difference in CES scores was found (seclusion median score=.40, [range 1.1-4.2]; restraint median score=2.59 [range 1.1-4.0]). CONCLUSIONS: The results do not provide evidence for using one intervention rather than the other. Clinical decisions should take into account patients' preferences. Randomized controlled trials of coercive interventions are feasible. Such studies contribute to the development of ethical and evidence-based guidelines.

Feasibility of randomized controlled trials on seclusion and mechanical restraint.

BACKGROUND: In psychiatry seclusion and mechanical restraint are most commonly used in the management of violence and self-directed aggression. Both interventions are considered as efficacious and indispensable. Yet, these measures can have deleterious effects on patients. The least restrictive alternative is recommended. Evidence about what kind of intervention is least restrictive is only scarcely available. Up to now, no randomized controlled trial (RCT) on this subject has been conducted. PURPOSE: To describe ethical, methodological and legal problems of RCTs on coercive interventions and to suggest possible solutions. METHODS: Literature research on possible study designs, ethical considerations and legal regulations was conducted in PubMed. RESULTS: Corresponding to the procedures in emergency medicine informed consent can be obtained after the intervention when the patients are capable again. Informed consent refers only to participation in an interview and utilization of data. Randomization can be ethically approved, if exclusion criteria for randomization are defined. A comprehensive cohort study seems to be the most practicable study design. As primary outcome variable an assessment of subjective experiences of the patients' restrictions to human rights.

Congenital dyserythropoietic anemia type I (CDA I): molecular genetics, clinical appearance, and prognosis based on long-term observation.

Congenital dyserythropoietic anemia type I (CDA I) is a rare autosomal recessive disorder with ineffective erythropoiesis and iron overloading. More than 100 cases have been described, but with the exception of a report on a large Bedouin tribe, these reports include only small numbers of cases, and no data on the lifetime evolution of the disease are available. Since 1967, we have been able to follow 21 cases from 19 families for up to 37 years. Twenty-one patients with a confirmed diagnosis of CDA I exhibited chronic macrocytic anemia of variable severity, requiring regular red cell transfusions only in 2 individuals. Four developed gallstones before the age of 30 years. Fifteen of 16 cases alive at the time of analysis showed mutations of at least one allele from exons 6 to 28 within CDAN1. Iron overloading is to be expected in all patients. In 9 patients, iron depletion was started between the ages of 7 and 36 years. Splenectomy, which was performed in 7 patients, did not result in improvement of hemoglobin values. Five patients were treated with interferon alpha-2a, and all responded with a rise in hemoglobin concentration of between 25 and 35 g/L (2.5 and 3.5 g/dL) starting within 4 weeks.

Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation.

Congenital dyserythropoietic anemia type II (CDA II) is the most frequent type of congenital dyserythropoietic anemia. More than 200 cases have been described, but with the exception of a report by the International CDA II Registry, these reports include only small numbers of cases and no data on the lifetime evolution of the disease. Since 1967, we were able to follow 48 cases of CDA II from 43 families for up to 35 years. All patients exhibit chronic anemia of variable severity requiring regular red cell transfusions only in a minority of children; 60% developed gallstones before the age of 30 years, and 16 patients had cholecystectomy between 8 and 34 years of age. Iron overload was a frequent complication. In 16 cases, iron depletion started between 7 and 36 years. Three patients died from secondary hemochromatosis. Splenectomy, performed in 22 cases, led to moderate increases in hemoglobin values and eliminated the need for transfusions but did not prevent further iron loading. The current recommendation is to consider splenectomy if the anemia compromises patients' performance, and to manage iron overload according to the guidelines derived from patients with thalassemia.