Summary
Background
Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the ...effectiveness of dose‐optimisation for ustekinumab nonresponse is limited.
Aim
To assess the effectiveness of dose escalation of ustekinumab.
Methods
This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard‐dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation.
Results
A total of 142 patients (22 centres/14 countries) were included. The patients were dose‐escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid‐free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow‐up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow‐up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission.
Conclusions
Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.
Background: Carotid-femoral pulse wave velocity (cfPWV), acknowledged as a reliable proxy of arterial stiffness, is an independent predictor of cardiovascular (CV) events. Carotid-femoral PWV is ...considered the gold standard for the estimation of arterial stiffness. cfPWV is a demanding, time consuming and expensive method, and an estimated PWV (ePWV) has been suggested as an alternative method when cfPWV is not available. Our aim was to analyze the predictive role of ePWV for CV and all-cause mortality in the general population. Methods: In a stratified random sample of 1086 subjects from the general Croatian adult population (EH-UH study) (men 42.4%, average age 53 ± 16), subjects were followed for 17 years. ePWV was calculated using the following formula: ePWV = 9.587 − 0.402 × age + 4.560 × 10−3 × age2 − 2.621 × 10−5 × age2 × MBP + 3.176 × 10−3 × age × MBP − 1.832 × 10−2 × MBP. MBP= (DBP) + 0.4(SBP − DBP). Results: At the end of the follow-up period, there were 228 deaths (CV, stroke, cancer, dementia and degenerative diseases, COLD, and others 43.4%, 10.5%, 28.5%, 5.2%, 3.1%, 9.3%, respectively). In the third ePWV tercile, we observed more deaths due to CV disease than to cancer (20.5% vs. 51.04%). In a Cox regression analysis, for each increase in ePWV of 1 m/s, there was a 14% increase risk for CV death. In the subgroup of subjects with higher CV risk, we found ePWV to be a significant predictor of CV deaths (ePWV (m/s) CI 1.108; p < 0.029; HR 3.03, 95% CI 1.118–8.211). Conclusions: In subjects with high CV risk, ePWV was a significant and independent predictor of CV mortality.
Aim
To evaluate the effects of vitamin D on transient elastography (TE, FibroScan) indices of liver steatosis (controlled attenuation parameter CAP) and fibrosis (liver stiffness measurement LSM) in ...adults with non‐alcoholic fatty liver disease (NAFLD).
Patients and Methods
In this randomized (2:1), double‐blind, single‐centre, 12‐month trial, patients with NAFLD were treated with vitamin D (1000 IU/day) (n = 201) or a matching placebo (n = 110). Two co‐primary outcomes were changes in CAP and LSM after 360 days of treatment versus baseline. Two main secondary outcomes were CAP/LSM changes after 180 days of treatment.
Results
Both CAP and LSM gradually decreased in vitamin D‐treated patients and slightly increased in the placebo arm. Vitamin D was superior to placebo for both primary outcomes (mean differences in CAP and LSM changes (−49.5 dB/m 95% CI −59.5 to −39.4 and −0.72 kPa 95% CI −1.43 to 0.00, respectively) and both secondary outcomes (−22.1 dB/m −32.1 to −12.1 and −0.89 kPa −1.61 to −0.17, respectively). Of a number of exploratory outcomes (change at 12 months vs. baseline), vitamin D reduced serum uric acid (−17.9 μmol/L −30.6 to −5.2), gamma‐glutamyltransferase (−8.9 IU/L −15.5 to −2.3) and fasting serum insulin levels (−5.1 pmol/L −9.3 to −0.8) as well as the homeostatic model assessment of insulin resistance index (−1.6 −3.1 to −0.2) (false discovery rate 5%‐adjusted P‐values between .0572 and .0952).
Conclusion
Low‐medium dose supplementation of vitamin D (1000 IU/day) over 12 months reduces TE indices of liver steatosis (CAP) and fibrosis (LSM) in NAFLD patients.
Aim
our aim was to explore the association between life habits and the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) as the surrogate markers of liver steatosis and ...fibrosis in a large cohort of non‐alcoholic fatty liver disease (NAFLD) patients.
Methods
In this prospective, cross‐sectional study we had analysed 1998 patients with diagnosed NAFLD. Sleeping duration was categorised in three groups: short (S) (<6 hours), moderate (M) (6‐8 hours) and long (L) (>8 hours) sleep duration. Coffee drinking was categorized into no (0), moderate (1‐2) and frequent (≥3) consumption (in cups/day). Smoking was categorised as yes versus no.
Results
Frequent coffee consumers had the lowest prevalence of obesity, hypertension, dyslipidaemia and diabetes. Furthermore, coffee non‐consumers had highest values of hepatic enzymes, CAP and LSM. Moderate sleep duration was associated with lower values of CAP and LSM. Coffee consumption was associated with lower CAP in all the multivariate models (CAP unadjusted and model 1, 2 and 3), with largest effect in most frequent coffee consumers (≥3, model 3). Also, most frequent coffee consumers were associated with lower LSM in unadjusted model, model 1 and 2, while this was not the case for model 3 and those who consumed 1‐2 cups of coffee per day. Reduced sleeping was confirmed as risk factor for elevated CAP in most of the models (unadjusted and model 1 and 2). Also, negative association of LSM was also confirmed in unadjusted model and model 2. Patients which slept 6‐8 hours per day were mostly associated with lower CAP and LSM. Smoking status was not associated with CAP or LSM values.
Conclusion
Coffee consumption has beneficial effect on CAP and LSM and this effect is dose dependent since and independent of a variety of relevant confounders. We have shown that moderate sleep duration has also beneficial effect on CAP and LSM.
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