How to inform at-risk relatives?:Attitudes of 1379 Dutch patients, relatives, and members of the general population

The uptake of predictive DNA testing in families with a hereditary disease is <50%. Current practice often relies on the proband to inform relatives about the possibility of predictive DNA testing, but not all relatives are informed adequately. To enable informed decision-making concerning predictive DNA testing, the approach used to inform at-risk relatives needs to be optimized. This study investigated the preferences of patients, relatives, and the general population from the Netherlands on how to inform relatives at risk of autosomal dominant diseases. Online surveys were sent to people with autosomal dominant neuro-, onco-, or cardiogenetic diseases and their relatives via patient organizations (n = 379), and to members of the general population via a commercial panel (n = 1,000). Attitudes of the patient and population samples generally corresponded. A majority believed that initially only first-degree relatives should be informed, following the principles of a cascade screening approach. Most participants also thought that probands and healthcare professionals (HCPs) should be involved in informing relatives, and a large proportion believed that HCPs should contact relatives directly in cases where patients are unwilling to inform, both for untreatable and treatable conditions. Participants from the patient sample were of the opinion that HCPs should actively offer support. Our findings show that both patients and HCPs should be involved in informing at-risk relatives of autosomal dominant diseases and suggest that relatives' 'right to know' was considered a dominant issue by the majority of participants. Further research is needed on how to increase proactive support in informing of at-risk relatives

Temporal dynamics of depression, cognitive performance and sleep in older persons with depressive symptoms and cognitive impairments:a series of eight single-subject studies

OBJECTIVES: To investigate the presence, nature and direction of the daily temporal association between depressive symptoms, cognitive performance and sleep in older individuals. DESIGN, SETTING, PARTICIPANTS: Single-subject study design in eight older adults with cognitive impairments and depressive symptoms. MEASUREMENTS: For 63 consecutive days, depressive symptoms, working memory performance and night-time sleep duration were daily assessed with an electronic diary and actigraphy. The temporal associations of depressive symptoms, working memory and total sleep time were evaluated for each participant separately with time-series analysis (vector autoregressive modeling). RESULTS: For seven out of eight participants we found a temporal association between depressive symptoms and/or sleep and/or working memory performance. More depressive symptoms were preceded by longer sleep duration in one person (r = 0.39; p < .001), by longer or shorter sleep duration than usual in one other person (B = 0.49; p < .001), by worse working memory in one person (B = -0.45; p = .007), and by better working memory performance in one other person (B = 0.35; p = .009). Worse working memory performance was preceded by longer sleep duration (r = -.35; p = .005) in one person, by shorter or longer sleep duration in three other persons (B = -0.76; p = .005, B = -0.61; p < .001; B = -0.34; p = .002), and by more depressive symptoms in one person (B = -0.25; p = .009). CONCLUSION: The presence, nature and direction of the temporal associations between depressive symptoms, cognitive performance and sleep differed between individuals. Knowledge of personal temporal associations may be valuable for the development of personalized intervention strategies in order to maintain their health, quality of life, functional outcomes and independence

Understanding the diagnostic delay in rare diseases

According to the European definition, rare diseases are life-threatening or chronically debilitating conditions that affect only 5 out of 10,000 people in the European Union. It is estimated that there are around 6000-8000 different rare diseases, affecting 6-8% of the population in the course of their lives. For the Netherlands, this means that about 1 million people are affected by a rare disease, or one in 17 people. Patients with rare diseases indicate that they often have a long and uncertain diagnostic journey behind them, while the first symptoms present in childhood in 75% of the rare diseases. In this perspective, we discuss some of the results from the research report 'Scherperzicht op diagnostischevertragingbijzeldzameaandoeningen' in which the diagnostic journey for patients with rare diseases is mapped out with figures. We also make recommendations to speed up the diagnostic process for patients with rare diseases.</p

Linked 3-D modelling of megathrust earthquake-tsunami events: from subduction to tsunami run up

How does megathrust earthquake rupture govern tsunami behaviour? Recent modelling advances permit evaluation of the influence of 3-D earthquake dynamics on tsunami genesis, propagation, and coastal inundation. Here, we present and explore a virtual laboratory in which the tsunami source arises from 3-D coseismic seafloor displacements generated by a dynamic earthquake rupture model. This is achieved by linking open-source earthquake and tsunami computational models that follow discontinuous Galerkin schemes and are facilitated by highly optimized parallel algorithms and software. We present three scenarios demonstrating the flexibility and capabilities of linked modelling. In the first two scenarios, we use a dynamic earthquake source including time-dependent spontaneous failure along a 3-D planar fault surrounded by homogeneous rock and depth-dependent, near-lithostatic stresses. We investigate how slip to the trench influences tsunami behaviour by simulating one blind and one surface-breaching rupture. The blind rupture scenario exhibits distinct earthquake characteristics (lower slip, shorter rupture duration, lower stress drop, lower rupture speed), but the tsunami is similar to that from the surface-breaching rupture in run-up and length of impacted coastline. The higher tsunami-generating efficiency of the blind rupture may explain how there are differences in earthquake characteristics between the scenarios, but similarities in tsunami inundation patterns. However, the lower seafloor displacements in the blind rupture result in a smaller displaced volume of water leading to a narrower inundation corridor inland from the coast and a 15 per cent smaller inundation area overall. In the third scenario, the 3-D earthquake model is initialized using a seismo-thermo-mechanical geodynamic model simulating both subduction dynamics and seismic cycles. This ensures that the curved fault geometry, heterogeneous stresses and strength and material structure are consistent with each other and with millions of years of modelled deformation in the subduction channel. These conditions lead to a realistic rupture in terms of velocity and stress drop that is blind, but efficiently generates a tsunami. In all scenarios, comparison with the tsunamis sourced by the time-dependent seafloor displacements, using only the time-independent displacements alters tsunami temporal behaviour, resulting in later tsunami arrival at the coast, but faster coastal inundation. In the scenarios with the surface-breaching and subduction-initialized earthquakes, using the time-independent displacements also overpredicts run-up. In the future, the here presented scenarios may be useful for comparison of alternative dynamic earthquake-tsunami modelling approaches or linking choices, and can be readily developed into more complex applications to study how earthquake source dynamics influence tsunami genesis, propagation and inundation

Тактика лечения эректильной дисфункции у мужчин без партнерши

Обосновывается актуальность проблемы оказания помощи мужчинам с эректильной дисфункцией, не имеющим сексуальной партнерши. Описаны предложенные автором подходы к коррекции нарушения сексуального здоровья мужчин и лечебные тактики.The importance of the issue of rendering the aid to the men with erectile dysfunction who do not have a female partner is substantiated. The author describes the original approaches to correction of the sexual health in the men and therapeutic tactics

Acute neuropsychiatry:a confused patient and a puzzled doctor

BACKGROUND: Anti-NMDA-receptor-encephalitis is a progressive autoimmune disease with significant mortality if left untreated.CASE DESCRIPTION: A 58-year-old man without previous psychiatric or neurologic history presented at the emergency department after brief loss of consciousness at work. Within a few hours, the patient developed acute neuropsychiatric symptoms, including altered levels of consciousness, aggression, incoherence, change in behaviour, and psychomotor agitation. Initially, additional blood, cerebrospinal fluid and EEG tests showed no abnormalities. Over the course of the following days, catatonia, orofacial dyskinesia and autonomic-function disorder developed, eventually with respiratory insufficiency, necessitating transfer to the intensive-care unit. At this stage, the EEG did show abnormalities, and cerebrospinal fluid analysis showed marginal pleocytosis. The patient was treated with intravenous methylprednisolone and immunoglobins. Anti-NMDA-receptor antibodies were present in the blood and cerebrospinal fluid. Screening for malignancy identified small-cell lung carcinoma, for which the patient was treated with cytostatic agents.CONCLUSION: Acute neuropsychiatric symptoms in a middle-aged patient with no psychiatric medical history are suggestive of an underlying somatic cause. Timely recognition and treatment of anti-NMDA-receptor encephalitis is essential to improve the prognosis.</p