High-precision stereotactic irradiation for focal drug-resistant epilepsy versus standard treatment: a randomized waitlist-controlled trial (the PRECISION trial).

INTRODUCTION: The standard treatment for patients with focal drug-resistant epilepsy (DRE) who are not eligible for open brain surgery is the continuation of anti-seizure medication (ASM) and neuromodulation. This treatment does not cure epilepsy but only decreases severity. The PRECISION trial offers a non-invasive, possibly curative intervention for these patients, which consist of a single stereotactic radiotherapy (SRT) treatment. Previous studies have shown promising results of SRT in this patient population. Nevertheless, this intervention is not yet available and reimbursed in the Netherlands. We hypothesize that: SRT is a superior treatment option compared to palliative standard of care, for patients with focal DRE, not eligible for open surgery, resulting in a higher reduction of seizure frequency (with 50% of the patients reaching a 75% seizure frequency reduction at 2 years follow-up). METHODS: In this waitlist-controlled phase 3 clinical trial, participants are randomly assigned in a 1:1 ratio to either receive SRT as the intervention, while the standard treatments consist of ASM continuation and neuromodulation. After 2-year follow-up, patients randomized for the standard treatment (waitlist-control group) are offered SRT. Patients aged ≥ 18 years with focal DRE and a pretreatment defined epileptogenic zone (EZ) not eligible for open surgery will be included. The intervention is a LINAC-based single fraction (24 Gy) SRT treatment. The target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations. The seizure frequency will be monitored on a daily basis using an electronic diary and an automatic seizure detection system during the night. Potential side effects are evaluated using advanced MRI, cognitive evaluation, Common Toxicity Criteria, and patient-reported outcome questionnaires. In addition, the cost-effectiveness of the SRT treatment will be evaluated. DISCUSSION: This is the first randomized trial comparing SRT with standard of care in patients with DRE, non-eligible for open surgery. The primary objective is to determine whether SRT significantly reduces the seizure frequency 2 years after treatment. The results of this trial can influence the current clinical practice and medical cost reimbursement in the Netherlands for patients with focal DRE who are not eligible for open surgery, providing a non-invasive curative treatment option. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05182437. Registered on September 27, 2021.

Introduction of a new scoring tool to identify clinically stable heart failure patients.

INTRODUCTION: Heart failure (HF) poses a burden on specialist care, making referral of clinically stable HF patients to primary care a desirable goal. However, a structured approach to guide patient referral is lacking. METHODS: The Maastricht Instability Score-Heart Failure (MIS-HF) questionnaire was developed to objectively stratify the clinical status of HF patients: patients with a low MIS-HF (0-2 points, indicating a stable clinical condition) were considered for treatment in primary care, whereas high scores (> 2 points) indicated the need for specialised care. The MIS-HF was evaluated in 637 consecutive HF patients presenting between 2015 and 2018 at Maastricht University Medical Centre. RESULTS: Of the 637 patients, 329 (52%) had a low score and 205 of these 329 (62%) patients were referred to primary care. The remaining 124 (38%) patients remained in secondary care. Of the 308 (48%) patients with a high score (> 2 points), 265 (86%) remained in secondary care and 41 (14%) were referred to primary care. The primary composite endpoint (mortality, cardiac hospital admissions) occurred more frequently in patients with a high compared to those with a low MIS-HF after 1 year of follow-up (29.2% vs 10.9%; odds ratio (OR) 3.36, 95% confidence interval (CI) 2.20-5.14). No significant difference in the composite endpoint (9.8% vs 12.9%; OR 0.73, 95% CI 0.36-1.47) was found between patients with a low MIS-HF treated in primary versus secondary care. CONCLUSION: The MIS-HF questionnaire may improve referral policies, as it helps to identify HF patients that can safely be referred to primary care.

Amino acid digestibility and energy content of deoiled (solvent-extracted) corn distillers dried grains with solubles for swine and effects on growth performance and carcass characteristics.

A study with 3 experiments was conducted to determine the AA digestibility and energy concentration of deoiled (solvent-extracted) corn distillers dried grains with solubles (dDGS) and to evaluate its effect on nursery pig growth performance, finishing pig growth performance, and carcass traits. In Exp. 1, a total of 5 growing barrows (initial BW = 30.8 kg) were fitted with a T-cannula in the distal ileum and allotted to 1 of 2 treatments: 1) a diet with dDGS as the sole protein source, or 2) a N-free diet for determining basal endogenous AA losses in a crossover design at 68.0 kg of BW. Apparent and standardized (SID) ileal digestibility of AA and energy concentration of dDGS were determined. In Exp. 2, a total of 210 pigs (initial BW = 9.9 kg) were used in a 28-d experiment to evaluate the effect of dDGS on nursery pig performance. Pigs were allotted to 5 dietary treatments (0, 5, 10, 20, or 30% dDGS) formulated to contain equal ME (increased added fat with increasing dDGS) and SID Lys concentrations based on the values obtained from Exp. 1. In Exp. 3, a total of 1,215 pigs (initial BW = 29.6 kg) were used in a 99-d experiment to determine the effect of dDGS on growth and carcass characteristics of finishing pigs. Pigs were allotted to dietary treatments similar to those used in Exp. 2 and were fed in 4 phases. The analyzed chemical composition of dDGS in Exp. 1 was 35.6% CP, 5.29% ash, 4.6% fat, 18.4% ADF, and 39.5% NDF on a DM basis. Apparent ileal digestibility values of Lys, Met, and Thr in dDGS were 47.2, 79.4, and 64.1%, respectively, and SID values were 50.4, 80.4, and 68.9%, respectively. The determined GE and DE and the calculated ME and NE values of dDGS were 5,098, 3,100, 2,858, and 2,045 kcal/kg of DM, respectively. In Exp. 2, nursery pig ADG, ADFI, and G:F were similar among treatments. In Exp. 3, increasing dDGS reduced (linear; P < 0.01) ADG and ADFI but tended to improve (linear; P = 0.07) G:F. Carcass weight and yield were reduced (linear; P < 0.01), loin depth tended to decrease (linear; P = 0.09), and carcass fat iodine values increased (linear; P < 0.01) as dDGS increased. No difference was observed in backfat, percentage of lean, or fat-free lean index among treatments. In conclusion, dDGS had greater CP and AA but less energy content than traditional distillers dried grains with solubles. In addition, when dietary fat was added to diets to offset the reduced ME content, feeding up to 30% dDGS did not affect the growth performance of nursery pigs but did negatively affect the ADG, ADFI, and carcass fat quality of finishing pigs.