Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

MRI monitoring of drug delivery using thermosensitive magnetoliposomes

Since the beginning of the 20th century the constant increase of the cancer incidence in the developed world has led to extensive research to improve the effectiveness of treatments, including chemotherapy. While chemotherapy has shown success in several indications it is also limited by toxicity. Local drug delivery by hyperthermia-induced drug release from thermosensitive liposomes (TSL) may reduce systemic toxicity of chemotherapy, while maintaining or increasing its efficacy. To achieve increased drug concentration locally at the correct location, imaging guidance is necessary, and can be applied to monitoring the accumulation of the carrier, the application of hyperthermia and the release of the drug. In this thesis, labeling of the thermosensitive nanocarriers based on superparamagnetic iron oxide is evaluated. In addition we developed dedicated MRI methods for monitoring the accumulation, as well as for release and temperature monitoring that could be used to guide such a procedure. In chapter 2 the effect of Thermosensitive magnetoliposomes (TSM), i.e. ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) encapsulated in thermosensitive liposomes, on MRI contrast was studied. Monitoring temperature triggered drug release using MR requires dedicated imaging protocols. In chapter 3 the feasibility of using a multi-echo spoiled gradient echo for the time resolved assessment of R1, R2* and temperature maps for use with TSM was developed. The 5s dynamic multi-echo sequence can be used straightforwardly to map R2* from the decreasing echo amplitudes, as well as the temperature based on PRFS using the unwrapped phase change. However, R1 is not directly accessible. The method estimates the R1-change based on the signal magnitude change knowing the value of R2* and compensating for the apparent proton density changes with temperature. In chapter 4, we investigated whether TSM in combination with time-resolved MR relaxation mapping and thermometry techniques implemented previously allowed assessment of intratumoral distribution of nanocarriers as well as their release profile in vivo. In this in vivo study, local hyperthermia was applied for 5 to 15 min in tumor-bearing rats (N=6) using a homemade MR-compatible dual water bath setup that allowed for increasing the temperature into one tumor while maintaining the temperature of the other tumor constant, which could thus serve as a control. In chapter 5 we describe the formulation of a thermosensitive liposome encapsulating both Gd-chelate and citrated-USPIO, so called Gd-TSM. Thus we used citrated USPIOs to label the liposome while Gd-chelates were used to monitor the release. The Gd-TSM formulation was characterized using DLS and Cryo-TEM and compared to two other formulation encapsulating either Gd‑chelate or citrated USPIO alone, and no significant hydrodynamic changes were observed. Contrary to the formulation from chapter 2, the citrated USPIOs were found to stay entrapped in the liposome lumen after a heat-induced phase transition on Cryo-TEM

Time between inhibitor detection and start of immune tolerance induction: Association with outcome in the BrazIT study

Background Immune tolerance induction (ITI) is the treatment of choice for eradication of anti-factor VIII (FVIII) neutralizing alloantibodies (inhibitors) in people with inherited hemophilia A and high-responding inhibitor (PwHA-HRi). The association between ITI outcome and time elapsed between inhibitor detection and start of ITI ( increment t(inhi-ITI)) is debatable. Objective The aim of this study was to evaluate this association among a large cohort of severe PwHA-HRi. Methods Severe (factor VIII activity level 0.6-1.7 year), third (>1.7-9.2 years), and fourth quartile (>9.2-24.5 years). The overall success rate was 65.5% (93/142), with no difference among first, second, third, and fourth quartiles (62.9%, 69.4%, 58.3%, and 71.4%, respectively) even after adjusting the analyses for potential confounders. Conclusion In conclusion, delayed ITI start is not associated with failure of ITI in PwHA-HRi. Therefore, ITI should be offered for these patients, regardless of the time elapsed between the detection of inhibitor and the ITI start.Clinical epidemiolog