The primary objective of this trial was to assess safety and anti-inflammatory effects of an add-on training program involving breathing exercises, cold exposure, and meditation in patients with ...axial spondyloarthritis.
This study was an open-label, randomised, one-way crossover clinical proof-of-concept trial. Twenty-four patients with moderately active axial spondyloarthritis(ASDAS >2.1) and hs-CRP ≥5mg/L were included and randomised to an intervention (n = 13) and control group (n = 11) group that additionally received the intervention after the control period. The intervention period lasted for 8 weeks. The primary endpoint was safety, secondary endpoints were change in hs-CRP, serum calprotectin levels and ESR over the 8-week period. Exploratory endpoints included disease activity measured by ASDAS-CRP and BASDAI, quality of life (SF-36, EQ-5D, EQ-5D VAS), and hospital anxiety and depression (HADS).
We found no significant differences in adverse events between groups, with one serious adverse event occurring 8 weeks after end of the intervention and judged 'unrelated'. During the 8-week intervention period, there was a significant decline of ESR from (median interquartile range to 16 9-26.5 to 9 5-23 mm/hr, p = 0.040, whereas no effect was found in the control group (from 14 8.3-27.3 to 16 5-37 m/hr, p = 0.406). ASDAS-CRP declined from 3.1 2.5-3.6 to 2.3 1.9-3.2 in the intervention group (p = 0.044). A similar trend was observed for serum calprotectin (p = 0.064 in the intervention group versus p = 0.182 in the control group), but not for hs-CRP.
This proof-of-concept study in axial spondyloarthritis met its primary endpoint with no safety signals during the intervention. There was a significant decrease in ESR levels and ASDAS-CRP upon the add-on training program in the intervention group. These findings warrant full-scale randomised controlled trials of this novel therapeutic approach in patients with inflammatory conditions.
ClinicalTrials.gov; NCT02744014.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Heart failure (HF) is a serious complication and often the cause of death in adults with congenital heart disease (CHD). Therefore, our aims were to determine the frequency of ...HF-admissions, and to assess risk factors of first HF-admission and of mortality after first HF-admission in adults with CHD. Methods The Dutch CONCOR registry was linked to the Hospital Discharge Registry and National Mortality Registry to obtain data on HF-admissions and mortality. Risk factors for both HF-admission and mortality were assessed using Cox regression models. Results Of 10,808 adult patients (49% male), 274 (2.5%) were admitted for HF during a median follow-up period of 21 years. The incidence of first HF-admission was 1.2 per 1000 patient-years, but the incidence of HF itself will be higher. Main defect, multiple defects, and surgical interventions in childhood were identified as independent risk factors of HF-admission. Patients admitted for HF had a five-fold higher risk of mortality than patients not admitted (hazard ratio (HR) = 5.3; 95% confidence interval 4.2–6.9). One- and three-year mortality after first HF-admission were 24% and 35% respectively. Independent risk factors for three-year mortality after first HF-admission were male gender, pacemaker implantation, admission duration, non-cardiac medication use and high serum creatinine. Conclusions The incidence of HF-admission in adults with CHD is 1.2 per 1000 patient-years. Mortality risk is substantially increased after HF-admission, which emphasises the importance to identify patients at high risk of HF-admission. These patients might benefit from closer follow-up and earlier medical interventions. The presented risk factors may facilitate surveillance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective
As first‐degree relatives (FDRs) of HLA–B27–positive patients with axial spondyloarthritis (SpA) have an increased risk of developing axial SpA, the objectives were 1) to evaluate the ...presence of highly specific imaging features as well as clinical signs of SpA at baseline and after 1 year of follow‐up, and 2) to describe the evolution toward clinical disease within 1 year of follow‐up in a cohort of seemingly healthy FDRs of HLA–B27–positive axial SpA patients.
Methods
The Pre‐SpA cohort is a 5‐year prospective inception cohort of seemingly healthy FDRs of HLA–B27–positive axial SpA patients. Clinical and imaging features were collected and recorded.
Results
At baseline, 19% of the FDRs reported inflammatory back pain, 32% current arthralgia, 3% arthritis (ever), 5% enthesitis (ever), and 1% dactylitis (ever), and 3% had an extraarticular manifestation. C‐reactive protein level was elevated in 16%, and erythrocyte sedimentation rate was elevated in 7%. On magnetic resonance imaging (MRI) views of sacroiliac joints, 10% had a Spondyloarthritis Research Consortium of Canada score of ≥2, 4% had a score of ≥5, and 4% had deep lesions. In total, 1% fulfilled the modified New York criteria for radiographic sacroiliitis. Clinical, MRI, and acute phase findings were equally distributed between HLA–B27–positive and –negative FDRs. After 1 year of follow‐up, clinical parameters did not change on the group level, but 6% of the FDRs were clinically diagnosed with axial SpA, of whom 86% were HLA–B27–positive.
Conclusion
Features associated with SpA or imaging abnormalities were found in up to 32% of seemingly healthy FDRs, with an equal distribution between HLA–B27–positive and –negative FDRs. Progression to clinical axial SpA within 1 year of follow‐up was mainly observed in HLA–B27–positive FDRs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
If TNF inhibitors are initiated in the early stages of psoriatic arthritis, this could potentially modulate disease and therefore allow us to discontinue the TNF inhibitor after achieving remission.
...To investigate whether remission induced by tumour necrosis factor alpha inhibitor (TNFi) and methotrexate in patients with early psoriatic arthritis is sustained after withdrawal of TNFi.
Open-label extension of a recently published double-blind, randomized placebo-controlled trial. Patients with psoriatic arthritis fulfilling the CASPAR criteria and with active disease at baseline (swollen and tender joint count ≥ 3) were randomized to either golimumab and methotrexate or matched placebo and methotrexate. Patients in Disease Activity Score (DAS) remission at week 22 continued in the open-label extension on methotrexate monotherapy. The primary end point was the percentage of patients in DAS-CRP remission (DAS < 1.6) at week 50.
Eight patients from the original placebo group and 18 patients from the original TNFi group continued in the extension phase. At week 50, 6 out of 8 (75%) patients from the original MTX (methotrexate) group versus 10 out of 18 (56%) patients from the original MTX+TNFi group were in DAS-CRP remission (p = 0.347). Considering the total study population, 6 out of 24 (25%) of the original MTX group versus 10 out of 26 (38.5%) of the original MTX+TNFi group were in DAS remission at week 50 (p = 0.308).
Remission achieved by initial combination treatment with TNFi and methotrexate in early psoriatic arthritis is maintained on methotrexate monotherapy in approximately half of the patients.
Registered at Clinicaltrials.gov with number NCT01871649 on June 7, 2013.
The Antarctic Ice Sheet (AIS) is out of equilibrium with the current anthropogenic‐enhanced climate forcing. Paleoenvironmental records and ice sheet models reveal that the AIS has been tightly ...coupled to the climate system during the past and indicate the potential for accelerated and sustained Antarctic ice mass loss into the future. Modern observations by contrast suggest that the AIS has only just started to respond to climate change in recent decades. The maximum projected sea level contribution from Antarctica to 2100 has increased significantly since the Intergovernmental Panel on Climate Change (IPCC) 5th Assessment Report, although estimates continue to evolve with new observational and theoretical advances. This review brings together recent literature highlighting the progress made on the known processes and feedbacks that influence the stability of the AIS. Reducing the uncertainty in the magnitude and timing of the future sea level response to AIS change requires a multidisciplinary approach that integrates knowledge of the interactions between the ice sheet, solid Earth, atmosphere, and ocean systems and across time scales of days to millennia. We start by reviewing the processes affecting AIS mass change, from atmospheric and oceanic processes acting on short time scales (days to decades), through to ice processes acting on intermediate time scales (decades to centuries) and the response to solid Earth interactions over longer time scales (decades to millennia). We then review the evidence of AIS changes from the Pliocene to the present and consider the projections of global sea level rise and their consequences. We highlight priority research areas required to improve our understanding of the processes and feedbacks governing AIS change.
Plain Language Summary
The Antarctic Ice Sheet (AIS) is an important component of the global climate system. Human activities have caused the atmosphere and especially the oceans to warm. However, the full effect of human caused climate change on the AIS has not currently been realized because the ice sheet responds on a range of time scales and to many different Earth processes. Modern observations show that West Antarctica has been melting at an accelerating rate since the 2000s, while the data for East Antarctica are less clear. Environmental records preserve the history of the climate and AIS, which extend beyond the instrumental record and reveal how the AIS responded to past climate warming. Estimates of how much the AIS will contribute to sea level rise by the Year 2100 have changed as a result of new information on how the AIS evolved in the past and research into the interactions between the ice sheet, solid Earth atmosphere, and ocean systems. This review brings together our knowledge of the major processes and feedbacks affecting the AIS and the evidence for how the ice sheet changed since the Pliocene. We consider the future estimates and consequences of global sea level rise from melting of the AIS and highlight priority research areas.
Key Points
The AIS is a highly dynamic component of the Earth system, evolving on a broad range of temporal and spatial scales
Paleoenvironmental evidence highlights the centennial to millennial response time scales of the AIS to atmospheric‐ocean forcing
Coupling feedbacks in Earth system components are required to reduce the uncertainty in AIS's contribution to past and future sea level rise
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Objectives
Earlier retrospective studies have suggested a relation between DISH and cardiovascular disease, including myocardial infarction. The present study assessed the association ...between DISH and incidence of cardiovascular events and mortality in patients with high cardiovascular risk.
Methods
In this prospective cohort study, we included 4624 patients (mean age 58.4 years, 69.6% male) from the Second Manifestations of ARTerial disease cohort. The main end point was major cardiovascular events (MACE: stroke, myocardial infarction and vascular death). Secondary endpoints included all-cause mortality and separate vascular events. Cause-specific proportional hazard models were used to evaluate the risk of DISH on all outcomes, and subdistribution hazard models were used to evaluate the effect of DISH on the cumulative incidence. All models were adjusted for age, sex, body mass index, blood pressure, diabetes, non-HDL cholesterol, packyears, renal function and C-reactive protein.
Results
DISH was present in 435 (9.4%) patients. After a median follow-up of 8.7 (IQR 5.0–12.0) years, 864 patients had died and 728 patients developed a MACE event. DISH was associated with an increased cumulative incidence of ischaemic stroke. After adjustment in cause-specific modelling, DISH remained significantly associated with ischaemic stroke (HR 1.55; 95% CI: 1.01, 2.38), but not with MACE (HR 0.99; 95% CI: 0.79, 1.24), myocardial infarction (HR 0.88; 95% CI: 0.59, 1.31), vascular death (HR 0.94; 95% CI: 0.68, 1.27) or all-cause mortality (HR 0.94; 95% CI: 0.77, 1.16).
Conclusion
The presence of DISH is independently associated with an increased incidence and risk for ischaemic stroke, but not with MACE, myocardial infarction, vascular death or all-cause mortality.
Unhealthy dietary habits are an important risk factor for cardiovascular disease (CVD) and adopting a healthy diet is a central recommendation in CVD prevention. This study assessed the dietary ...habits of patients with established CVD, their compliance to dietary guidelines, and the relationship between guideline-compliance and recurrent cardiovascular event risk.
2656 patients with established CVD from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART) prospective cohort study, were included between 1996 and 2022. Data on dietary intake was retrospectively collected for all participants in December 2022 using a 160-item food frequency questionnaire. Compliance with dietary guidelines was quantified using an amended version of the Dutch Healthy Diet 2015 (DHD-15) index (range: 0-135). Cox proportional hazard models were used to quantify the relationship with cardiovascular events (stroke and myocardial infarction).
Among 2656 CVD patients (77% male, mean age 59 ± 9 years), median energy intake was 1922 IQR: 1536-2351 kcal/day. The median DHD-15 index was 81.7 IQR 71.2-92.0, with high compliance scores for recommendations on legumes and fish, and low scores for recommendations on whole grains, red meat, processed meat, and dairy. A higher DHD-15 score was associated with lower stroke risk (HR 0.78, 95% CI 0.66-0.92 per 10-point increase) but not with myocardial infarction.
Compliance with dietary guidelines was suboptimal in patients with established CVD. High compliance was associated with a clinically significant reduction in stroke risk in patients with established CVD, emphasizing the importance of dietary counseling.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval ...dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID.
Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4–7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated.
255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms.
Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.
•Many natalizumab treated MS patients experience wearing-off symptoms.•Extension of natalizumab treatment intervals does not increase wearing-off symptoms.•Wearing-off symptoms are not related to natalizumab drug concentrations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Survival of kidney transplant recipients (KTR) is low compared with the general population. Low muscle mass and muscle strength may contribute to lower survival, but practical measures of ...muscle status suitable for routine care have not been evaluated for their association with long‐term survival and their relation with each other in a large cohort of KTR.
Methods
Data of outpatient KTR ≥ 1 year post‐transplantation, included in the TransplantLines Biobank and Cohort Study (ClinicalTrials.gov Identifier: NCT03272841), were used. Muscle mass was determined as appendicular skeletal muscle mass indexed for height2 (ASMI) through bio‐electrical impedance analysis (BIA), and by 24‐h urinary creatinine excretion rate indexed for height2 (CERI). Muscle strength was determined by hand grip strength indexed for height2 (HGSI). Secondary analyses were performed using parameters not indexed for height2. Cox proportional hazards models were used to investigate the associations between muscle mass and muscle strength and all‐cause mortality, both in univariable and multivariable models with adjustment for potential confounders, including age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR) and proteinuria.
Results
We included 741 KTR (62% male, age 55 ± 13 years, BMI 27.3 ± 4.6 kg/m2), of which 62 (8%) died during a median interquartile range follow‐up of 3.0 2.3–5.7 years. Compared with patients who survived, patients who died had similar ASMI (7.0 ± 1.0 vs. 7.0 ± 1.0 kg/m2; P = 0.57), lower CERI (4.2 ± 1.1 vs. 3.5 ± 0.9 mmol/24 h/m2; P < 0.001) and lower HGSI (12.6 ± 3.3 vs. 10.4 ± 2.8 kg/m2; P < 0.001). We observed no association between ASMI and all‐cause mortality (HR 0.93 per SD increase; 95% confidence interval CI 0.72, 1.19; P = 0.54), whereas CERI and HGSI were significantly associated with mortality, independent of potential confounders (HR 0.57 per SD increase; 95% CI 0.44, 0.81; P = 0.002 and HR 0.47 per SD increase; 95% CI 0.33, 0.68; P < 0.001, respectively), and associations of CERI and HGSI with mortality remained independent of each other (HR 0.68 per SD increase; 95% CI 0.47, 0.98; P = 0.04 and HR 0.53 per SD increase; 95% CI 0.36, 0.76; P = 0.001, respectively). Similar associations were found for unindexed parameters.
Conclusions
Higher muscle mass assessed by creatinine excretion rate and higher muscle strength assessed by hand grip strength are complementary in their association with lower risk of all‐cause mortality in KTR. Muscle mass assessed by BIA is not associated with mortality. Routine assessment using both 24‐h urine samples and hand grip strength is recommended, to potentially target interdisciplinary interventions for KTR at risk for poor survival to improve muscle status.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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