The Use of Expanded Carrier Screening in Reproductive Medicine: Scientific Impact Paper No. 74.

Expanded carrier screening (ECS) is a genetic screening test carried out by analysing a blood sample. This screen can be used to detect whether the individual unknowingly carries gene variants associated with common genetic conditions, such as cystic fibrosis, that may be passed on to their children. It is typically performed in reproductive medicine for those who are considering having a family either naturally or via fertility treatment. Many donor sperm and egg banks, particularly in the USA and Europe, also perform blanket ECS testing on all their prospective sperm and egg donors. ECS is not currently routine practice in the UK, but a growing number of patients are requesting it before treatment. All of us carry gene variants of some sort that may cause autosomal recessive disease in their children if their partner or donor also carry a variant in the same gene. An autosomal recessive disease means two copies of an abnormal gene must be present in order for the disease or trait (such as cystic fibrosis or sickle cell disease) to develop. One copy of the variant means the person is a carrier but does not have the condition. Two copies, i.e. from the mother and father, means the child has a 25% chance of having the genetic disease. Carrying a gene variant does not mean that the individual would necessarily have any symptoms of the disease or any features of the condition. Genetic tests for specific conditions are currently available either before or during pregnancy for prospective parents who have a family or personal history of a genetic condition, or for those from ethnic backgrounds where certain conditions - such as haemoglobinopathies (blood disorders) - are common, prompting referral to a clinical genetics department. Expanded carrier screens may test for more than 100 genetic conditions. The list of conditions screened for is called a panel. Common panels are 250 or 600 genes. Not all expanded carrier screens that are available analyse the same genes. Some may test for genes that do not cause serious disease, or cause diseases that occur in later life; others test for genes that cause severe conditions in childhood. There is no agreement as to which panel of genes should be tested for in an ECS. Understanding the screening that is being offered, and the meaning of any results, is complicated and requires support from appropriately trained professionals to best inform the prospective parent or parents.

[Recurrent intracerebral haemorrhage in a 24-year-old female patient]. / Rezidivierende intrazerebrale Blutungen bei einer 24-jährigen Patientin.

A 24-year-old female patient from Sierra Leone was referred to the authors' hospital after several unclear intracerebral bleeding events and an echogenic structure on the aortic valve. The patient was receiving oral anticoagulation therapy due to paroxysmal atrial fibrillation and left ventricular noncompaction. Fluorescence in situ hybridization in combination with polymerase chain reaction and sequencing revealed infective endocarditis of the mitral and aortic valve caused by Bartonella quintana. In retrospect, the intracerebral bleeding events could be identified as septic emboli with secondary haemorrhagic transformation under anticoagulation therapy. The patient showed significant clinical improvement and no further bleeding events occurred after receiving biological mitral and aortic valve replacement and several weeks of doxycycline and gentamicin antibiotic therapy.

[Evidence based community psychiatric community health care services in Germany: taking inventory]. / Evidenzbasierung gemeindepsychiatrischer Versorgungsangebote in Deutschland: eine Bestandsaufnahme.

PURPOSE AND METHODS: One of the outcomes of reforming mental health care in Germany has been the establishment of a range of community mental health services. However, current evidence for the effectiveness of these services is slight. Based on a literature search this article provides a systematic overview of empirical research in this sphere. In detail, social psychiatric services, crisis centres, psychosocial contact points, day care centres, and various models of supported housing and work/employment are assessed. Available results on effectiveness are classified according to their level of scientific evidence. RESULTS: The current state of research is characterised by the situation that effectiveness of the care approach provided by social psychiatric services and some types of supported housing and work/employment has been demonstrated at a medium level of scientific evidence. In contrast, the evidence level of mental health care provided in crisis centres, psychosocial contact points, and day care centres is poor. CONCLUSION: The major reasons for this lack of research are: heterogeneity of care models and staffing levels in the different community mental health services, lack of standardised documentation and reporting system in these services, and lack of research culture to utilise routine outcome data. The consequences of aiming at increasing the level of scientific evidence in this sphere would be to intensify funding of research projects and to implement high quality research designs such as randomised controlled trials.

Clinical experience with temporary vena caval filters.

PURPOSE: To look at the benefits and complications of different vena caval filters inserted prophylactically. Three temporarily implantable caval filter systems were used in 67 patients. MATERIALS AND METHODS: Twelve Cook filters (six transjugular, six transfemoral), 11 Angiocor filters (one transjugular, 10 transbrachial), and 44 Antheor filters (three transjugular, four transfemoral, 37 transbrachial) were successfully implanted. In known iliac vein or caval thrombosis, the prophylactic filters were placed during thrombolytic therapy in 46 cases, surgery in 17 cases, thrombosis in pregnancy in three cases, and high-dose heparinization without lysis in one case. RESULTS: One patient had a fatal pulmonary embolism during treatment; seven thrombi were detected in the filter. Other complications were caused either by the underlying therapy alone (one fatal outcome of abdominal aorta aneurysmal surgery, two cases of cerebral hemorrhage, two cases of retroperitoneal hematomas, two cases of streptokinase fever reactions, one compartment syndrome, two cases of macrohematuria), by the combination of therapy and caval filter implantation (three cases of groin hematomas, three cases of arm hematomas), or by filter implantation alone (two cases of subclavian vein thrombosis, one catheter infection, one dislocation, one air embolism, one basket rupture). The bleeding complications were related to the aggressive thrombolytic therapy and would have occurred without filter implantation. CONCLUSION: Because temporary caval filters have no long-term complications per se, their use seems sensible as long as there are stringent indications, including the presence of iliac vein or caval thrombosis and risk of thrombus mobilization. The Antheor filter system was the most convenient system for implantation.

In vitro studies of temporary vena cava filters.

PURPOSE: To evaluate the clot trapping capacity of different temporary vena cava filters in a vena cava model. METHODS: A vena cava flow model was built using PVC tubing, a hemodialysis membrane and a pulsatile pump. Blood was imitated by a Dextran 40 solution. Five different temporary vena cava filters and two prototypes were tested using human thrombi. The mechanism of clot capture was observed. RESULTS: Decreasing rank order according to decreasing percentage of clots captured for the 21-mm diameter vena cava model was Cook (C) > Angiocor (A) > Cordis (CD) > Antheor (TF-6) > DIL for thrombi with a diameter of 3 mm and A > C > CD > TF-6 > DIL for 5-mm thrombi. In a cava with diameter of 28 mm, decreasing rank order was C > CD = A > TF-6 > DIL and C > CD = A > DIL > TF-6 for 3- and 5-mm thrombi, respectively. Two new prototypes, the TF-8 and TF-10 filters, achieved better results than the TF-6 filter and were in most conditions comparable to the A and CD filters. In most cases, thrombi were trapped between filter and cava wall. CONCLUSION: The vena cava flow model demonstrates significant differences in rates of clot capture (range 22%-98%) depending on cava diameter, thrombus size, and filter type.