Adherence to direct oral anticoagulant treatment for atrial fibrillation in the Netherlands: A surveillance study.

BACKGROUND: Adherence to direct oral anticoagulants (DOACs) in patients with atrial fibrillation in every day practice may be less than in clinical trials. AIMS: To assess adherence to DOACs in atrial fibrillation patients in every day practice and identify predictors for non-adherence. METHODS: Individual linked dispensing data of atrial fibrillation patients who used DOACs were obtained from the Foundation for Pharmaceutical Statistics covering the Netherlands between 2012 and 2016. One year adherence to DOAC was calculated for initial DOAC as proportion of days covered (PDC) ≥80% and the association between clinical variables and adherence was assessed using logistic regression. In addition, we measured non-persistence, that is, patients who completely stopped their initial DOAC within 1 year follow-up. RESULTS: A total of 4797 apixaban-, 20 454 rivaroxaban- and 18 477 dabigatran users were included. The mean age was 69 years (n = 43 910), which was similar for the DOAC types. The overall proportion of patients with PDC ≥80% was 76%, which was highest for apixaban- (87%), followed by dabigatran- (80%) and rivaroxaban (69%) users. Multivariable analyses revealed that age ≤60 years, no concomitant drug use were predictors for non-adherence. Of atrial fibrillation patients who continued treatment, 97% had a PDC ≥80%, compared with only 56% for those who discontinued their DOAC treatment within 1 year. CONCLUSIONS: Non-adherence to DOACs was associated with age ≤60 years and no concomitant drugs use. Non-adherence was higher in patients who later discontinued DOAC treatment. Results of our study support research into interventions to improve adherence.

Evaluation of cervical screening strategies with adjunct high-risk human papillomavirus testing for women with borderline or mild dyskaryosis.

The management of women with a smear read as borderline/mild dyskaryosis (BMD) found by cervical cancer screening is still under discussion as only few of these cases are associated with high-grade lesions. To determine the optimal screening strategy for these women, a simulation model of cervical cancer development was used that is based on high-risk human papillomavirus (hrHPV) infection. The current strategy of repeat cytological testing at 6 and 18 months after BMD was compared to strategies with adjunct hrHPV testing. Calculations were done for both conventional and liquid-based cytology as the primary screening tool. In comparison to current screening, adjunct hrHPV testing was more effective in preventing cancer and more woman-friendly (reduction in colposcopy referrals with outcome < cervical intraepithelial neoplasia (CIN2) of up to 56% and in repeat smears of 30-100%). In combination with conventional cytology, cost-effective strategies were the ones in which a sample for high-risk human papillomavirus (hrHPV) testing is collected at a return visit within 1 month or in which hrHPV testing is restricted to repeat smears taken at 6 and 18 months. For these strategies, co-collection of samples for hrHPV testing at baseline is not necessary which has organizational and cost advantages. In combination with liquid-based cytology, it was cost-effective to perform a reflex hrHPV test at baseline from the liquid-based specimen. Liquid-based screening was more effective than conventional screening, but annual diagnosis costs were euro5 million higher (population size 16 million). In conclusion, our calculations indicate that implementation of hrHPV testing for the management of women with borderline or mild dyskaryosis (BMD) is feasible both in settings where conventional and liquid-based cytology is current practice.

Natural history and screening model for high-risk human papillomavirus infection, neoplasia and cervical cancer in the Netherlands.

A simulation model is presented that assumes that persistent infection with high-risk human papillomavirus (hrHPV) is a necessary cause of cervical cancer. For the estimation of the model parameters, data of recent Dutch follow-up studies were reanalyzed. The predicted incidences of cervical cancer, cervical intraepithelial neoplasia (CIN1, CIN2 and CIN3) and abnormal cytology were validated with nationwide figures and population-based screening results. The model predicted a lifetime risk for cervical cancer of 2.9% with a peak at age 48 years. The predicted lifetime risk dropped to 0.4% when attending cervical screening. For women who were not hrHPV infected at 30 years, the lifetime risk was 1.6%. Sensitivity analyses were performed to check natural history assumptions that were only weakly identified from available data sets. The incidence of CIN3 observed with screening appeared a useful clinical end point as the predicted incidence was robust against changes in the sensitivity of cervical cytology and the duration to CIN3. The model can be used to study the health-economic benefits that can be achieved in nationwide screening when including an hrHPV test.