Number of Affected Relatives, Age, Smoking, and Hypertension Prediction Score for Intracranial Aneurysms in Persons with a Family History for Subarachnoid Hemorrhage

Background: Persons with a positive family history of aneurysmal subarachnoid hemorrhage are at increased risk of aneurysmal subarachnoid hemorrhage. Preventive screening for intracranial aneurysms (IAs) in these persons is cost-effective but not very efficient. We aimed to develop and externally validate a model for predicting the probability of an IA at first screening in persons with a positive family history of aneurysmal subarachnoid hemorrhage. Methods: For model development, we studied results from initial screening for IA in 660 prospectively collected persons with ≥2 affected first-degree relatives screened at the University Medical Center Utrecht. For validation, we studied results from 258 prospectively collected persons screened in the University Hospital of Nantes. We assessed potential predictors of IA presence in multivariable logistic regression analysis. Predictive performance was assessed with the C statistic and a calibration plot and corrected for overfitting. Results: IA were present in 79 (12%) persons in the development cohort. Predictors were number of affected relatives, age, smoking, and hypertension (NASH). The NASH score had a C statistic of 0.68 (95% CI, 0.62-0.74) and showed good calibration in the development data. Predicted probabilities of an IA at first screening varied from 5% in persons aged 20 to 30 years with two affected relatives, without hypertension who never smoked, up to 36% in persons aged 60 to 70 years with ≥3 affected relatives, who have hypertension and smoke(d). In the external validation data IA were present in 67 (26%) persons, the model had a C statistic of 0.64 (95% CI, 0.57-0.71) and slightly underestimated IAs risk. Conclusions: For persons with ≥2 affected first-degree relatives, the NASH score improves current predictions and provides risk estimates for an IA at first screening between 5% and 36% based on 4 easily retrievable predictors. With the information such persons can now make a better informed decision about whether or not to undergo preventive screening

A cost-effectiveness analysis of screening for intracranial aneurysms in persons with one first-degree relative with subarachnoid haemorrhage

Introduction: Although persons with one first-degree relative with aneurysmal subarachnoid haemorrhage have an increased risk of aneurysm formation and aneurysmal subarachnoid haemorrhage, screening them for unruptured intracranial aneurysms was not beneficial in a modelling study from the 1990s. New data on the risk of aneurysmal subarachnoid haemorrhage in these persons and improved treatment techniques call for reassessment of the cost-effectiveness of screening. Patients and methods: We used a cost-effectiveness analysis using a Markov model and Monte Carlo simulation comparing screening and preventive aneurysm treatment with no screening in persons with one first-degree relative with aneurysmal subarachnoid haemorrhage. We analyzed the impact on quality-adjusted life years, costs and net health benefit of single screening (at varying screening age) and serial screening (with varying screening age and intervals) using a cost-effectiveness threshold of €20,000/quality-adjusted life year. Results: In 17 of the 24 strategies assessed, additional costs for screening for unruptured intracranial aneurysm were <€20,000 per quality-adjusted life year gained. The strategy with highest net health benefit was screening at age 40 and 55. Screening every five years from age 20 to 70 yielded the highest health benefits at the highest additional costs. Discussion: Based on current risks of aneurysmal subarachnoid haemorrhage and complications of preventive treatment, several strategies to screen for unruptured intracranial aneurysm in persons with one first-degree relative with aneurysmal subarachnoid haemorrhage are cost effective compared with no screening, when applying a cost-effectiveness threshold of €20,000/quality-adjusted life year. Conclusion: We recommend discussing with persons at risk the option of screening twice, at age 40 and 55, which will result overall in substantial health benefits at acceptable additional costs

High treatment uptake in human immunodeficiency virus/ hepatitis C virus-coinfected patients after unrestricted access to direct-acting antivirals in the Netherlands

Background The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Methods Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Results Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa–based regimen had failed in 54. Conclusions Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients