A Toolkit to assess health needs for congenital disorders in low- and middle-income countries: an instrument for public health action.

BACKGROUND: In 2010 the World Health Assembly called for action to improve the care and prevention of congenital disorders, noting that technical guidance would be required for this task, especially in low- and middle-income countries. Responding to this call, we have developed a freely available web-accessible Toolkit for assessing health needs for congenital disorders. METHODS: Materials for the Toolkit website (http://toolkit.phgfoundation.org) were prepared by an iterative process of writing, discussion and modification by the project team, with advice from external experts. A customized database was developed using epidemiological, demographic, socio-economic and health-services data from a range of validated sources. Document-processing and data integration software combines data from the database with a template to generate topic- and country-specific Calculator documents for quantitative analysis. RESULTS: The Toolkit guides users through selection of topics (including both clinical conditions and relevant health services), assembly and evaluation of qualitative and quantitative information, assessment of the potential effects of selected interventions, and planning and prioritization of actions to reduce the risk or prevalence of congenital disorders. CONCLUSIONS: The Toolkit enables users without epidemiological or public health expertise to undertake health needs assessment as a prerequisite for strategic planning in relation to congenital disorders in their country or region.

Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: a literature-based systematic HuGE review and meta-analysis.

Multiple genes have been studied for potential associations with lung cancer. The gene most frequently associated with increased risk has been glutathione S-transferase M1 (GSTM1). The glutathione S-transferase enzyme family is known to catalyze detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. In this review, the authors summarize the available evidence associating lung cancer with the GSTM1 gene. They describe results from an updated meta-analysis of 98 published genetic association studies investigating the relation between the GSTM1 null variant and lung cancer risk including 19,638 lung cancer cases and 25,266 controls (counting cases and controls in each study only once). All studies considered, the GSTM1 null variant was associated with an increased risk of lung cancer (odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.14, 1.30), but no increase in risk was seen (OR = 1.01, 95% CI: 0.91, 1.12) when only the five largest studies (>500 cases each) were considered. Furthermore, while GSTM1 null status conferred a significantly increased risk of lung cancer to East Asians (OR = 1.38, 95% CI: 1.24, 1.55), such a genotype did not confer increased risk to Caucasians. More data regarding the predictive value of GSTM1 genetic testing are needed before population-based testing may be reasonably considered.

Cost Effectiveness of Using Array-CGH for Diagnosing Learning Disability.

OBJECTIVE: To undertake a cost-effectiveness analysis of using microarray comparative genomic hybridisation (array-CGH) as a first-line test versus as a second-line test for the diagnosis of causal chromosomal abnormalities in patients referred to a NHS clinical genetics service in the U.K. with idiopathic learning disability, developmental delay and/or congenital anomalies. METHODS: A cost-effectiveness study was conducted. The perspective is that of a U.K. NHS clinical genetics service provider (with respect to both costs and outcomes). A cohort of patients (n = 1590) referred for array-CGH testing of undiagnosed learning disability and developmental delay by a single NHS regional clinical genetics service (South East Thames Regional Genetics Service), were split into a before-and-after design where 742 patients had array-CGH as a second-line test (before group-comparator intervention) and 848 patients had array-CGH as a first-line test (after group-evaluated intervention). The mean costs were calculated from the clinical genetics testing pathway constructed for each patient including the costs of genetic testing undertaken and clinical appointments scheduled. The outcome was the number of diagnoses each intervention produced so that a mean cost-per-diagnosis could be calculated. The cost effectiveness of the two interventions was calculated as an incremental cost-effectiveness ratio to produce an incremental cost-per-diagnosis (in 2013 GBP). Sensitivity analyses were conducted by altering both costs and effects to check the validity of the outcome. RESULTS: The incremental mean cost of testing patients using the first-line testing strategy was -GBP241.56 (95% CIs -GBP256.93 to -GBP226.19) and the incremental mean gain in the percentage diagnoses was 0.39% (95% CIs -2.73 to 3.51%), which equates to an additional 1 diagnosis per 256 patients tested. This cost-effectiveness study comparing these two strategies estimates that array-CGH first-line testing dominates second-line testing because it was both less costly and as effective. The sensitivity analyses conducted (adjusting both costs and effects) supported the dominance of the first-line testing strategy (i.e. lower cost and as effective). CONCLUSIONS: The first-line testing strategy was estimated to dominate the second-line testing strategy because it was both less costly and as effective. These findings are relevant to the wider UK NHS clinical genetics service, with two key strengths of this study being the appropriateness of the comparator interventions and the direct applicability of the patient cohort within this study and the wider UK patient population.

Inherited cardiovascular conditions: the challenges of genomic medicine.

The report Heart to Heart published in 2009 by the Foundation for Genomics and Population Health provided an account of new health services needs arising from greater scientific and clinical understanding of inherited cardiovascular conditions. Informed by advice from an expert working group, the report makes recommendations for the development of specialised inherited cardiovascular conditions services within the UK. The report will also be of relevance internationally, wherever cardiologists and geneticists aim to provide care for these patients and their families.