The Global State of the Genetic Counseling Profession.

The profession of genetic counseling (also called genetic counselling in many countries) began nearly 50 years ago in the United States, and has grown internationally in the past 30 years. While there have been many papers describing the profession of genetic counseling in individual countries or regions, data remains incomplete and has been published in diverse journals with limited access. As a result of the 2016 Transnational Alliance of Genetic Counseling (TAGC) conference in Barcelona, Spain, and the 2017 World Congress of Genetic Counselling in the UK, we endeavor to describe as fully as possible the global state of genetic counseling as a profession. We estimate that in 2018 there are nearly 7000 genetic counselors with the profession established or developing in no less than 28 countries.

Brain abnormalities in patients with Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with variability in clinical manifestations and molecular causes. In most cases, patients with BWS have normal development. Cases with developmental delay are usually attributed to neonatal hypoglycemia or chromosome abnormalities involving copy number variation for genes beyond the critical BWS region at 11p15.5. Brain abnormalities have not previously been recognized within the BWS phenotypic spectrum. We report on seven cases of BWS associated with posterior fossa abnormalities. Of these, two cases presented with Blake's pouch cyst, two with Dandy-Walker variant (DWV; hypoplasia of the inferior part of the vermis), one with Dandy-Walker malformation (DWM) and one with a complex of DWM, dysgenesis of the corpus callosum and brain stem abnormality. In all these cases, molecular findings involved the centromeric imprinted domain on chromosome locus 11p15.5, which includes imprinting center 2 (IC2) and the imprinted growth suppressor gene, CDKN1C. Three cases had loss of methylation at IC2, two had CDKN1C mutations, and one had loss of methylation at IC2 and a microdeletion. In one case no mutation/methylation abnormality was detected. These findings together with previously reported correlations suggest that genes in imprinted domain 2 at 11p15.5 are involved in normal midline development of several organs including the brain. Our data suggest that brain malformations may present as a finding within the BWS phenotype when the molecular etiology involves imprinted domain 2. Brain imaging may be useful in identifying such malformations in individuals with BWS and neurodevelopmental issues.

Malignant bowel obstruction: natural history of a heterogeneous patient population followed prospectively over two years.

CONTEXT: The management of malignant bowel obstruction (MBO) is often challenging and frequently involves multiple treatment modalities, including chemotherapy, surgery, stenting, and symptomatic medical management. OBJECTIVES: To describe the natural history of patients diagnosed with MBO who were admitted to a tertiary level hospital and followed by a multidisciplinary team that included medical oncologists, surgical oncologists, and palliative care specialists. METHODS: Thirty-five patients admitted under medical or surgical oncology with a diagnosis of MBO were followed over a two-year period or until the time of death. Primary malignancies included colon, rectum, pancreas, biliary, breast, bladder, carcinoid, renal cell, gastric, lung, and melanoma. Clinical outcomes of interest included survival, percentage of patients receiving surgery and/or chemotherapy, total parenteral nutrition (TPN), insertion of venting gastrostomy tube, disposition, and rates of readmission to hospital. RESULTS: Median survival was 80 days and three patients were alive at the time of study closure. At our center, 34% of patients underwent surgical intervention, 37% received at least one dose of post-MBO chemotherapy, and 43% received TPN. There was a cohort of patients (17%) who were alive at one year. CONCLUSION: Interventions such as chemotherapy and TPN may be appropriate in a carefully selected subgroup of patients. A collaborative approach is required for the optimal clinical management and palliation of MBO.

Evaluating correlation and interrater reliability for four performance scales in the palliative care setting.

Performance scales are used by clinicians to objectively represent a patient's level of function and have been shown to be important predictors of response to therapy and survival. Four different scales are commonly used in the palliative care setting, two of which were specifically developed to more accurately represent this population. It remains unclear which scale is best suited for this setting. The objectives of this study were to determine the correlations among the four scales and concurrently compare interrater reliability for each. Patients were each assessed at the same point in time by three different health care professionals, and all four scales were used to rate each patient. Spearman correlation coefficient values and both weighted and unweighted kappa values were calculated to determine correlation and interrater reliability. The results confirmed highly significant linear correlation among and between all four scales. Whether using a reliability measure that incorporates the concept of "partial credit" for "near misses" or a measure reflecting exact rater agreement, no one scale emerged as having a significantly higher likelihood of agreement among raters. We propose that what may be more important than clinical experience or rater profession is the level of training an individual health care professional rater receives on the administration of any particular performance scale. In addition, given that low levels of exact rater agreement could have substantial clinical implications for patients, we suggest that this parameter be considered in the design of future comparative studies.

A single set of numerical cutpoints to define moderate and severe symptoms for the Edmonton Symptom Assessment System.

Symptom intensity in cancer and palliative care patients is frequently assessed using a 0-10 ranking score. Results are then often grouped into verbal categories (mild, moderate, or severe) to guide therapy. Numerical cutpoints separating these categories are often variable, with previous work suggesting different cutpoints across different symptoms, which is unwieldy for clinical use. The Edmonton Symptom Assessment Symptom (ESAS) assesses nine common symptoms using this 0-10 scale. The primary aim of this study was to examine the relationship between the numerical and verbal scores using the ESAS and to identify a single cutpoint to separate severe from nonsevere symptomatology. A second goal was to similarly identify a cutpoint to separate moderate or severe from none or mild symptom intensity. Consenting patients (n=400) completed both a standard ESAS and an identical form that replaced 0-10 with none, mild, moderate, and severe. Receiver operating characteristic curves were generated to identify the best fit between sensitivity and specificity. For the "severe" ranking, six symptoms had a best fit of 7, with sensitivity for the remaining three symptoms still greater than 80%. For the combined grouping of moderate or severe, results were less uniform. A cutpoint of either 4 or 5 would be supported by our data, with a greater sensitivity using 4 and improved specificity using 5 as the cutpoint. Across all ESAS symptoms, then, 7 or higher represents a severe symptom by patient definition, whereas a cutpoint of either 4 or 5 could reasonably define combined moderate and severe symptoms.