Long-term follow-up of retrograde colonic irrigation for defaecation disturbances

Objective. Irrigation of the distal part of the large bowel is a nonsurgical alternative for patients with defaecation disturbance. In our institution, all patients with defaecation disturbances, not responding to medical treatment and biofeedback therapy, were offered retrograde colonic irrigation (RCI). This study is aimed at evaluating the long-term feasibility and outcome of RCI. Methods. Between 1989 and 2001, a consecutive series of 267 patients was offered RCI. All patients received instructions about RCI by one of our enterostomal therapists. Twenty-eight patients were lost to follow-up. A detailed questionnaire was sent by mail to 239 patients. The total response rate was 79% (190 patients). Based on the returned questionnaires it became clear the 21 (11%) patients never started RCI. The long-term feasibility and outcome of RCI was therefore assessed in the remaining group of 169 patients. Thirty-two patients were admitted with soiling, 71 patints with faecal incontinence, 37 patients with obstructed defaecation and 29 had defaecation disturbance after low anterior resection or pouch surgery. Results. According to the returned questionnaires, RCI was considered effective by 91 (54%) patients. Among patients with soling and faecal incontinence, RCI was found to be effective in, respectively, 47 and 41% of the subjects. Despite of the reported effectiveness, 10 (67%) patients with soiling and 5 (17%) patients with faecal incontinence decide to stop. Among patients with obstructed defaecation and those with defaecation disturbances after low anterior resection or pouch surgery the effectiveness of RCI was found to be 65 and 79%, respectively. None of these patients ceased their therapy. The overall succes-rate of long-term RCI was therefore 45%. Conclusions. Long-term RCI is beneficial for 45% of patients with defaecation disturbance. In the group of patients who considered RCI effective and beneficial, discontinuation of therapy was only observe among those with soiling and faecal incontinence

A Delphi study to determine the European core curriculum for Master programmes in genetic counselling.

Genetic counsellors have been working in some European countries for at least 30 years. Although there are great disparities between the numbers, education, practice and acceptance of these professionals across Europe, it is evident that genetic counsellors and genetic nurses in Europe are working autonomously within teams to deliver patient care. The aim of this study was to use the Delphi research method to develop a core curriculum to guide the educational preparation of these professionals in Europe. The Delphi method enables the researcher to utilise the views and opinions of a group of recognised experts in the field of study; this study consisted of four phases. Phases 1 and 4 consisted of expert workshops, whereas data were collected in phases 2 and 3 (n=35) via online surveys. All participants in the study were considered experts in the field of genetic counselling. The topics considered essential for genetic counsellor training have been organised under the following headings: (1) counselling; (2) psychological issues; (3) medical genetics; (4) human genetics; (5) ethics, law and sociology; (6) professional practice; and (7) education and research. Each topic includes the knowledge, skills and attitudes required to enable genetic counsellors to develop competence. In addition, it was considered by the experts that clinical practice should comprise 50% of the educational programme. The core Master programme curriculum will enable current courses to be assessed and inform the design of future educational programmes for European genetic counsellors

A multiplex assay for the sensitive detection and quantification of male and female Plasmodium falciparum gametocytes.

BACKGROUND: The transmission of malaria to mosquitoes depends on the presence of gametocytes that circulate in the peripheral blood of infected human hosts. Sensitive estimates of the densities of female gametocytes (FG) and male gametocytes (MG) may allow the prediction of infectivity to mosquitoes and thus a molecular estimate of the human infectious reservoir for transmission. METHODS: A novel multiplex qRT-PCR assay with intron-spanning primers was developed for the parallel quantification of FG and MG. CCp4 (PF3D7_0903800) transcripts specific for FG and PfMGET (PF3D7_1469900) transcripts specific for MG were quantified in total nucleic acids. The assay was validated on sex-sorted gametocytes from culture material and on samples from clinical trials with gametocytocidal drugs. Synthetic RNA standards were generated for the two targets genes and calibrated against known gametocyte quantities. RESULTS: The limit of detection was determined at 0.1 male and 0.1 female gametocyte/µL, which was equal to the limit of quantification (LOQ) for MG, while the LOQ for FG was 1 FG/µL. Results from previously reported clinical trials that used separate gametocyte qRT-PCR assays for FG (targeting Pfs25) and MG (targeting PfMGET) were reproduced with the multiplex assay. High levels of agreement between separate assays and the multiplex approach were observed (R2 = 0.9473, 95% CI 0.9314-0.9632, for FG measured by transcript levels of Pfs25 in qRT-PCR or CCp4 in multiplex; R2 = 0.8869, 95% CI 0.8541-0.9197, for MG measured by PfMGET in either single or multiplex qRT-PCR). FG and MG transcripts were detected in pure ring stage parasites at 10,000- and 100,000-fold reduced frequency for CCp4 and PfMGET, respectively. The CCp4 and PfMGET transcripts were equally stable under suboptimal storage conditions. CONCLUSIONS: Gametocyte densities and their sex ratios can be determined in the presented one-step multiplex assay with higher throughput than single assays. The interpretation of low gametocyte densities at asexual parasite densities above 1000 parasites/µL requires caution to avoid false positive gametocyte signals from spurious transcript levels in ring stage parasites

Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts

Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts

How harmful is genetic testing for familial adenomatous polyposis (FAP) in young children; the parents' experience

Predictive genetic testing for familial adenomatous polyposis (FAP) is routinely offered to children at-risk from the age of 10 years onwards. Predictive testing for FAP at a younger age is debatable, because of absence of medical benefits. However, circumstances may arise when testing at a younger age (< 10 years) is appropriate. Currently, there is a lack of published experience with predictive testing of children at this young age. We evaluated 13 children who were tested for FAP at the age younger than 10 years; 7 mutation-carriers and 6 non-carriers. Parents of these children were re-contacted and open-ended semi-structured interviewed. None of the contacted parents regretted the timing of genetic testing. The major reasons for testing at the young age were (1) testing of all children in the family at the same moment; (2) certainty for the future; and (3) preparing the child for future surveillance. None of the parents observed changes in mental or physical health in their child after testing. Also, young genetic testing did not lead to colon surveillance before it was indicated. Genetic testing for FAP at a young age is experienced as causing no harm by parents. Future studies should evaluate children's own experiences with early genetic testing