Recommendations for reporting results of diagnostic genetic testing (biochemical,cytogenetic and molecular genetic)

Genetic test results can have considerable importance for patients, their parents and more remote family members. Clinical therapy and surveillance, reproductive decisions and genetic diagnostics in family members, including prenatal diagnosis, are based on these results. The genetic test report should therefore provide a clear, concise, accurate, fully interpretative and authoritative answer to the clinical question. The need for harmonizing reporting practice of genetic tests has been recognised by the External Quality Assessment (EQA), providers and laboratories. The ESHG Genetic Services Quality Committee has produced reporting guidelines for the genetic disciplines (biochemical, cytogenetic and molecular genetic). These guidelines give assistance on report content, including the interpretation of results. Selected examples of genetic test reports for all three disciplines are provided in an annexe.Diagnostic genetic testing is an extremely rapidly expanding area encompassing a broad range of laboratory investigations to analyse chromosomes (from classical karyotype to molecular cytogenetics), nucleic acids (DNA, RNA), proteins and metabolites used to detect heritable or somatic mutations, genotypes or phenotypes related to disease and health. Genetic testing requires particular consideration in that it is usually performed only once in a patient''s lifetime, and the results may have considerable importance for lifetime decisions not only for the individuals being tested but also for children and family. Interpreting and reporting variation in germline chromosomes, DNA sequences or their products is a heavy clinical responsibility for prediction of susceptibility to disease, patient diagnosis, prognosis, counselling, treatment or family planning. Providing a set of reporting frameworks that can be customised for different testing contexts but share some common principles could be beneficial to the practice of a number of laboratories, including non-OECD members and/or laboratories that do not participate in External Quality Assessments (EQA), and to laboratories with blurred boundaries between research and genetic testing services.Although several guidelines already exist for reporting the results of genetic testing,^1,2,3 these focus on molecular genetic testing and do not cover the other two branches of laboratory genetics, namely biochemical genetics and cytogenetics. Based on recent surveys of EQA results presented by some European EQA providers and the request from genetic laboratories for comprehensive reporting guidelines, it was considered that a unifying attempt to harmonise the reporting practice of genetic tests in Europe and neighbouring countries would be welcome.     

Clinical and economic consequences of vancomycin and fidaxomicin for the treatment of Clostridium difficile infection in Canada

BACKGROUND:

Clostridium difficile infection (CDI) represents a public health problem with increasing incidence and severity.

OBJECTIVE:

To evaluate the clinical and economic consequences of vancomycin compared with fidaxomicin in the treatment of CDI from the Canadian health care system perspective.

METHODS:

A decision-tree model was developed to compare vancomycin and fidaxomicin for the treatment of severe CDI. The model assumed identical initial cure rates and included first recurrent episodes of CDI (base case). Treatment of patients presenting with recurrent CDI was examined as an alternative analysis. Costs included were for study medication, physician services and hospitalization. Cost effectiveness was measured as incremental cost per recurrence avoided. Sensitivity analyses of key input parameters were performed.

RESULTS:

In a cohort of 1000 patients with an initial episode of severe CDI, treatment with fidaxomicin led to 137 fewer recurrences at an incremental cost of $1.81 million, resulting in an incremental cost of $13,202 per recurrence avoided. Among 1000 patients with recurrent CDI, 113 second recurrences were avoided at an incremental cost of $18,190 per second recurrence avoided. Incremental costs per recurrence avoided increased with increasing proportion of cases caused by the NAP1/B1/027 strain. Results were sensitive to variations in recurrence rates and treatment duration but were robust to variations in other parameters.

CONCLUSIONS:

The use of fidaxomicin is associated with a cost increase for the Canadian health care system. Clinical benefits of fidaxomicin compared with vancomycin depend on the proportion of cases caused by the NAP1/B1/027 strain in patients with severe CDI.     

Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).     

Human taurine metabolism: fluxes and fractional extraction rates of the gut, liver, and kidneys

Taurine is involved in numerous biological processes. However, taurine plasma level decreases in response to pathological conditions, suggesting an increased need. Knowledge on human taurine metabolism is scarce and only described by arterial-venous differences across a single organ. Here we present taurine organ fluxes using arterial-venous concentration differences combined with blood flow measurements across the 3 major organ systems involved in human taurine metabolism in patients undergoing hepatic surgery. In these patients, we collected blood from an arterial line, portal vein, hepatic vein, and renal vein, and determined blood flow of the hepatic artery, portal vein, and renal vein using Doppler ultrasound. Plasma taurine was determined by high-performance liquid chromatography, and net organ fluxes and fractional extraction rates were calculated. Seventeen patients were studied. No differences were found between taurine concentrations in arterial, portal venous, hepatic venous, and renal venous plasma. The only significant finding was a release of taurine by the portally drained viscera (P = .04). Our data show a net release of taurine by the gut. This probably is explained by the enterohepatic cycle of taurine. Future studies on human taurine metabolism are required to determine whether taurine is an essential aminosulfonic acid during pathological conditions and whether it should therefore be supplemented.     

Evidence,Policies and Practices: Continuities and Discontinuities in Mental Health Promotion in a Developing Country

The relationship between research evidence, policy and implementation is complex throughout the world, but where resources are scarce (especially in developing countries) there is a need to ensure rational implementation. With reference to a study on which we work, we show how the simple act of conducting research where resources are lacking affects implementability. We discuss five key issues with which researchers must engage if they wish to affect policy and implementation: evidence is not the only criterion by which implementation decisions are made, implementation decisions are often political rather than health-oriented in the narrow sense, there is often a difference in time scale between research enterprises and policy implementation, moving from research to the ‘real world’ requires engagement with existing organisational systems, and we need to be able to tell the difference between changes in rhetoric and changes in the real world. The broad international context of funding and the scientific community also affect how researchers work in developing countries. We suggest that engagement with these apparently ‘non-scientific’ concerns is essential to the work of researchers.     

Transfer of training effects in stroke patients with apraxia: An exploratory study

The goal of the present study was to examine the transfer of the effects of cognitive strategy training for stroke patients with apraxia from trained to non-trained tasks. In strategy training, the occurrence of transfer is expected as the training programme is aimed, not at relearning specific tasks, but at teaching patients new ways to handle the problems resulting from the impairment. Exploratory analyses were conducted on data previously collected in a randomised controlled trial on the efficacy of the strategy training. A total of 113 left hemisphere stroke patients were randomly assigned to a strategy training group and a group receiving occupational therapy as usual. Assessment of apraxia, motor functioning and activities of daily living (ADL) took place at baseline, after an eight-week treatment period, and five months after baseline. The primary outcome measure consisted of standardised ADL observations of trained and non-trained tasks. The analyses showed that in both treatment groups, the scores on the ADL observations for non-trained tasks improved significantly after eight weeks of training as compared with the baseline score. Change scores of non-trained activities were larger in the strategy training group as compared with the usual treatment group.

By using previously collected data we are able to illustrate the potential transfer of treatment effects in a large sample of stroke patients. We found indications for the occurrence of transfer, although the study was not originally designed for the purpose of evaluating transfer. Therefore these results are worth exploring more profoundly. We will further investigate our preliminary conclusions in a new prospective study which is specifically designed to examine the transfer of training effects.     

A comparative study of performance in simple and choice reaction time tasks between obese and healthy-weight children

This study investigated weight status related differences in executive functions and movement execution to determine whether or not childhood obesity is associated with impaired perceptual-motor function. Nineteen obese (OB) children (10 ♂ and 9 ♀, aged 6–12 years) and nineteen gender and age matched healthy-weight (HW) peers performed two computer-based reaction time tasks. For both the simple and four choice reaction time (SRT/CRT) task condition, absolute mean reaction time (RT) and movement time (MT) were determined and expressed as a percentage of total response time (RsT). During the SRT task, OB children were intrinsically slower than their HW peers as reflected by a significantly higher absolute RT, MT and RsT. In the CRT task, however, between-group differences were only present for RT and RsT, whereas absolute MT was comparable among OB and HW participants. As a result, the relative temporal structure of RsT significantly differed between BMI groups, with a greater RT percentage among the OB children. During the CRT condition, OB children probably await final decision-making with regard to the execution of their response movement, which then no longer needs to be adjusted. Our results therefore indicate the use of a more conservative strategy within the OB group, suggesting that childhood obesity is associated with impaired perceptual-motor function. Besides the widely accepted mechanical explanation, a better understanding of the mechanisms underlying OB children's motor incompetence is needed to set up appropriate interventions to tackle this deficit and indirectly address associated health-related problems.