27 years of prenatal diagnosis for Huntington disease in the United Kingdom.

PURPOSE: There is little long-term, population-based data on uptake of prenatal diagnosis for Huntington disease (HD), a late-onset autosomal dominant neurodegenerative disorder, and the effect of the availability of preimplantation genetic diagnosis (PGD) on families' decisions about conventional prenatal diagnosis is not known. We report trends in prenatal diagnosis and preimplantation diagnosis for HD in the United Kingdom since services commenced. METHODS: Long-term UK-wide prospective case record-based service evaluation in 23 UK Regional Genetic Centres 1988-2015, and four UK PGD centers 2002-2015. RESULTS: From 1988 to 2015, 479 prenatal diagnoses were performed in the UK for HD. An exclusion approach was used in 150 (31%). The annual rate of HD prenatal diagnosis has remained around 18 (3.5/million) over 27 years, despite a steady increase in the use of PGD for HD since 2002. CONCLUSION: Although increasing number of couples are choosing either direct or exclusion PGD to prevent HD in their offspring, both direct and exclusion prenatal diagnosis remain important options in a health system where both PGD and prenatal diagnosis are state funded. At-risk couples should be informed of all options available to them, preferably prepregnancy

Value of risk scores in the decision to palliate patients with ruptured abdominal aortic aneurysm

Background: The aim of this study was to develop a 48-h mortality risk score, which included morphology data, for patients with ruptured abdominal aortic aneurysm presenting to an emergency department, and to assess its predictive accuracy and clinical effectiveness in triaging patients to immediate aneurysm repair, transfer or palliative care. Methods: Data from patients in the IMPROVE (Immediate Management of the Patient With Ruptured Aneurysm: Open Versus Endovascular Repair) randomized trial were used to develop the risk score. Variables considered included age, sex, haemodynamic markers and aortic morphology. Backwards selection was used to identify relevant predictors. Predictive performance was assessed using calibration plots and the C-statistic. Validation of the newly developed and other previously published scores was conducted in four external populations. The net benefit of treating patients based on a risk threshold compared with treating none was quantified. Results: Data from 536 patients in the IMPROVE trial were included. The final variables retained were age, sex, haemoglobin level, serum creatinine level, systolic BP, aortic neck length and angle, and acute myocardial ischaemia. The discrimination of the score for 48-h mortality in the IMPROVE data was reasonable (C-statistic 0·710, 95 per cent c.i. 0·659 to 0·760), but varied in external populations (from 0·652 to 0·761). The new score outperformed other published risk scores in some, but not all, populations. An 8 (95 per cent c.i. 5 to 11) per cent improvement in the C-statistic was estimated compared with using age alone. Conclusion: The assessed risk scores did not have sufficient accuracy to enable potentially life-saving decisions to be made regarding intervention. Focus should therefore shift to offering repair to more patients and reducing non-intervention rates, while respecting the wishes of the patient and family

The influence of venous thromboembolism on quality of life and severity of chronic venous disease.

BACKGROUND: It is not known whether burden-of-illness differs in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. OBJECTIVE: To compare severity of disease and quality of life in chronic venous disease patients with and without prior venous thromboembolism. PATIENTS AND METHODS: The VEINES Study population is an international cohort of 1531 outpatients with chronic venous disease in Belgium, France, Italy and Canada. Clinical severity of chronic venous disease graded using the seven-category 'CEAP' scale, and quality of life using standardized generic (SF-36) and venous disease-specific (VEINES-QOL/Sym) questionnaires were compared in patients with and without venous thromboembolism. Multivariable analyses with adjustment for known confounders were used to examine associations between venous thromboembolism and quality of life. RESULTS: One hundred and fifty-one (10%) patients had prior venous thromboembolism. These patients had more severe chronic venous disease than those without venous thromboembolism (P <0.0001), including a higher frequency of healed or active ulcers (29% vs. 7%, respectively). Multivariable analyses controlling for age, sex, country, education, body mass index, years of chronic venous disease and comorbid conditions demonstrated that prior venous thromboembolism was an independent predictor of poorer generic quality of life (SF-36 Mental Component Summary score, P=0.047; SF-36 Physical Component Summary score, P=0.012) and venous disease-specific quality of life (VEINES-QOL, P = 0.0002; VEINES-Sym, P=0.009). CONCLUSIONS: Disease severity is worse and quality of life poorer in chronic venous disease patients with prior venous thromboembolism compared with patients with other forms of chronic venous disease. Our findings support the need for further research of interventions to prevent and treat the long-term complications of venous thromboembolism

Ventral medial prefrontal cortex neuronal ensembles mediate context-induced relapse to heroin

In a rat model of context-induced relapse to heroin, we identified sparsely distributed ventral medial prefrontal cortex (mPFC) neurons that were activated by the heroin-associated context. Selective pharmacogenetic inactivation of these neurons inhibited context-induced drug relapse. A small subset of ventral mPFC neurons formed neuronal ensembles that encode the learned associations between heroin reward and heroin-associated contexts; re-activation of these neuronal ensembles by drug-associated contexts during abstinence provoked drug relaps

Is a 'general' theory of addiction possible? A commentary on: a multistep general theory of transition to addiction

[No abstract available