Responsiveness Evaluation and Recommendation for Responder Thresholds for Endometriosis Health Profile-30: Analysis of Two Phase III Clinical Trials.

Objective: To evaluate the responsiveness of the Endometriosis Health Profile-30 (EHP-30) and ascertain score changes that are indicative of response to treatment. A post hoc analysis of two Phase III, double-blind, placebo-controlled, randomized clinical trials among women with moderate-to-severe endometriosis-associated pain (Elaris Endometriosis I and II [EM-I and EM-II]). Materials and Methods: EHP-30 core items and sexual relationship module were administered at day 1, month 3 (M3), and month 6 (M6) to monitor patient-reported impacts of endometriosis-related pain. A seven-response level Patient Global Impression of Change (PGIC) was administered at M3 and M6. Dysmenorrhea (DYS), nonmenstrual pelvic pain (NMPP), and dyspareunia (DYSP) were collected using a daily diary. Three psychometric approaches, "triangulation," were used to suggest responder thresholds for the EHP-30 domains. The three approaches were anchor- and distribution-based analyses and use of clinically relevant indicators (DYS, NMPP, DYSP). Results: EM-I and EM-II enrolled 871 and 815 women, respectively. All EHP-30 domains improved during the trials (M3, M6). Differences (p < 0.001) for all EHP-30 domains were found among the PGIC responses at M3 and M6, indicating greater change was associated with greater EHP-30 improvements. Large effect sizes were noted for all EHP-30 domains (EM-I range -0.59 to -1.80; EM-II range -0.52 to -1.59). EHP-30 thresholds of meaningful change ranged from -20 to -35, with greater changes indicating greater improvement in health status. Conclusion: Responder thresholds by EHP-30 domain are recommended to evaluate treatment efficacy. Clinicians can individualize goals of treatment by EHP-30 domain and track changes using the EHP-30.

[Hereditary Alzheimer's disease with amyloid angiopathy caused by amyloid precursor protein locus]. / Familiäre Alzheimer-Variante mit Amyloidangiopathie als Ausdruck einer APP-Gen-Duplikation.

We report a patient with early-onset autosomal dominant dementia. The CSF showed increased levels of tau protein and decreased amyloid beta (ratio 42:40) typical for Alzheimer's disease. Cerebral MRI revealed vascular lesions and white-matter changes around the posterior horns of the ventricles with only moderate atrophy of the brain. Susceptibility-weighted imaging detected multiple small hemorrhagic changes. Gene analysis revealed amyloid precursor protein (APP) locus duplication as the cause of hereditary Alzheimer's dementia. The co-occurrence of CSF changes typical for Alzheimer's disease and MRI findings of cerebral amyloid angiopathy is remarkable, as it is also described for APP locus duplication. In conjunction with a family history suggestive of hereditary dementia, such a constellation should lead to enhanced gene analysis.

[Cortical amaurosis and status epilepticus with acute porphyria]. / Kortikale Amaurosis und Status epilepticus bei akuter Porphyrie.

The most common neurologic manifestations of acute intermittent porphyria (AIP) are autonomic visceral neuropathy, peripheral motor neuropathy, and CNS dysfunctions including seizures and neuropsychiatric disturbances. In rare instances, however, AIP patients have presented with acute cortical blindness. We present a 20-year-old woman who suffered her first attack of AIP. Following 1 week of abdominal pain, she was transferred from a surgical department because of sudden visual loss and deterioration of consciousness. On admission, she developed several generalized seizures. Magnetic resonance imaging showed bilateral DWI lesions occipitally and in the left anterior circulation. Cerebrospinal fluid, MR angiography, and duplex ultrasound were normal. On the following day, sedation and intubation became necessary because of a generalized status epilepticus. Analysis of porphyrinogens in blood, urine and stool showed significantly elevated values. Intravenous therapy with häm-arginate was initiated and antiepileptic therapy was changed to gagabentine. Under this therapeutical regime she remained stable and extubation was possible 48 h later.

The functional regulator (FR-3) of Fränkel.

This article describes the construction of the FR-3 appliance classically used in cases of Class III malocclusion characterized by maxillary skeletal retrusion. Included is a description of proper impression technique, construction bite registration, preparation of the work models, and a complete description of the fabrication of the FR-3 appliance. Specific steps in the clinical management of this appliance are also presented. The cephalometric records of three patients treated with the FR-3 appliance are then presented.