Wagener G.,Genzyme |
Baker B.F.,Isis Pharmaceuticals |
Geary R.S.,Isis Pharmaceuticals |
Donovan J.M.,Genzyme |
European Heart Journal | Year: 2012
Aims A randomized, double-blind, placebo-controlled study was conducted to investigate the safety and efficacy of mipomersen, an apolipoprotein B-100 (apoB) synthesis inhibitor, in patients who are statin intolerant and at high risk for cardiovascular disease (CVD). Methods and resultsThirty-three subjects, not receiving statin therapy because of statin intolerance, received a weekly subcutaneous dose of 200 mg mipomersen or placebo (2:1 randomization) for 26 weeks. The primary endpoint was per cent change in LDL cholesterol (LDL-c) from the baseline to Week 28. The other efficacy endpoints were per cent change in apoB and lipoprotein a [Lp(a)]. Safety was determined using the incidence of treatment-emergent adverse events (AEs) and clinical laboratory evaluations. After 26 weeks of mipomersen administration, LDL-c was reduced by 47 ± 18 (P < 0.001 vs. placebo). apoB and Lp(a) were also significantly reduced by 46 and 27, respectively (P < 0.001 vs. placebo). Four mipomersen (19) and two placebo subjects (17) discontinued dosing prematurely due to AEs. Persistent liver transaminase increases <3× the upper limit of normal were observed in seven (33) subjects assigned to mipomersen. In selected subjects, liver fat content was assessed, during and after treatment, using magnetic resonance spectroscopy. Liver fat content in these patients ranged from 0.8 to 47.3. Liver needle biopsy was performed in two of these subjects, confirming hepatic steatosis with minimal inflammation or fibrosis. ConclusionThe present data suggest that mipomersen is a potential therapeutic option in statin-intolerant patients at high risk for CVD. The long-term follow-up of liver safety is required.Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00707746 Published on behalf of the European Society of Cardiology. © The Author 2012.
Cheng Y.Y.Y.,Maastricht University |
Visser N.,Maastricht University |
Schouten J.S.,Maastricht University |
Wijdh R.-J.,University of Groningen |
And 6 more authors.
Ophthalmology | Year: 2011
Objective: To compare endothelial cell (EC) loss, visual and refractive outcomes, and complications after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). Design: Randomized, multicenter clinical trial. Participants: Fifty-six eyes of 56 patients with a corneal stromal pathology not affecting the endothelium were randomized to DALK or PK. Methods: The DALK procedure was performed according to Anwars big-bubble technique. Patients underwent an ophthalmic examination preoperatively and 3, 6, and 12 months postoperatively. Main Outcome Measures: Endothelial cell loss, refractive and topographic astigmatism, spherical equivalent, uncorrected visual acuity, and best spectacle-corrected visual acuity (BSCVA) were measured, and complications were recorded. Results: Endothelial cell loss was significantly higher after PK compared with DALK procedures performed without perforation of Descemets membrane (12 months: 27.7%±11.1% vs. 12.9%±17.6%). The BSCVA was significantly better in the PK group at 3 and 6 months after surgery but was not significantly different 12 months after surgery (0.39±0.3 logarithm of the minimum angle of resolution [logMAR] in DALK and 0.31±0.3 logMAR in PK). At 12 months postoperatively, refractive and topographic astigmatism in the DALK and PK groups were -3.37±2.3 diopters (D) and -3.76±2.1 D (P = 0.53), and 3.57±2.3 D and 4.16±2.0 D (P = 0.34), respectively. (Micro)perforation of the Descemets membrane occurred in 32% (9/28) of the DALK eyes, and 18% (5/28) of the patients required conversion to PK. Endothelial cell loss was not significantly different between DALK and PK when cases with perforation of Descemets membrane were included in the (intention-to-treat) analysis (12 months: 19.1±21.6 vs. 27.7±11.1 P = 0.112). Rejection episodes were reported in 1 patient in the DALK group (epithelial rejection) and 3 patients in the PK group (all endothelial rejections). No graft failure occurred. Conclusions: One year after DALK performed without perforation of Descemets membrane, EC loss is significantly lower, whereas the BSCVA is comparable to that in the PK group. In addition, no endothelial rejection occurred in the DALK group. However, Descemets membrane perforation remains a major complication in DALK and warrants improvements to standardize the big-bubble technique. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2011 American Academy of Ophthalmology.
Vennix S.,Erasmus Medical Center |
Mulder I.M.,Erasmus Medical Center |
Consten E.C.,Meander Medical Center |
Belgers E.H.,Atrium Medical |
And 10 more authors.
The Lancet | Year: 2015
Background Case series suggest that laparoscopic peritoneal lavage might be a promising alternative to sigmoidectomy in patients with perforated diverticulitis. We aimed to assess the superiority of laparoscopic lavage compared with sigmoidectomy in patients with purulent perforated diverticulitis, with respect to overall long-term morbidity and mortality. Methods We did a multicentre, parallel-group, randomised, open-label trial in 34 teaching hospitals and eight academic hospitals in Belgium, Italy, and the Netherlands (the Ladies trial). The Ladies trial is split into two groups: the LOLA group comparing laparoscopic lavage with sigmoidectomy and the DIVA group comparing Hartmann's procedure with sigmoidectomy plus primary anastomosis. The DIVA section of this trial is still underway but here we report the results of the LOLA section. Patients with purulent perforated diverticulitis were enrolled for LOLA, excluding patients with faecal peritonitis, aged older than 85 years, with high-dose steroid use (≤20 mg daily), and haemodynamic instability. Patients were randomly assigned (2:1:1; stratified by age [<60 years vs ≤60 years]) using secure online computer randomisation to laparoscopic lavage, Hartmann's procedure, or primary anastomosis in a parallel design after diagnostic laparoscopy. Patients were analysed according to a modified intention-to-treat principle and were followed up after the index operation at least once in the outpatient setting and after sigmoidoscopy and stoma reversal, according to local protocols. The primary endpoint was a composite endpoint of major morbidity and mortality within 12 months. This trial is registered with ClinicalTrials.gov, number NCT01317485. Findings Between July 1, 2010, and Feb 22, 2013, 90 patients were randomly assigned in the LOLA section of the Ladies trial when the study was terminated by the data and safety monitoring board because of an increased event rate in the lavage group. Two patients were excluded for protocol violations. The primary endpoint occurred in 30 (67%) of 45 patients in the lavage group and 25 (60%) of 42 patients in the sigmoidectomy group (odds ratio 1·28, 95% CI 0·54-3·03, p=0·58). By 12 months, four patients had died after lavage and six patients had died after sigmoidectomy (p=0·43). Interpretation Laparoscopic lavage is not superior to sigmoidectomy for the treatment of purulent perforated diverticulitis. Funding Netherlands Organisation for Health Research and Development. © 2015 Elsevier Ltd.
Cheng Y.Y.Y.,Maastricht University |
Van Den Berg T.J.T.P.,Netherlands Institute for Neuroscience |
Schouten J.S.,Maastricht University |
Pels E.,Cornea Bank Amsterdam |
And 5 more authors.
American Journal of Ophthalmology | Year: 2011
Purpose: To compare the quality of vision (straylight and contrast sensitivity) after femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS DSEK) and penetrating keratoplasty (PK). Design: Prospective, randomized clinical trial. Methods: setting: Multicenter (5 ophthalmic centers in The Netherlands). study population: Eighty eyes of 80 patients with corneal endothelial dysfunction were included and were randomized to FS DSEK or PK. observation procedures: FS DSEK and PK. main outcome measures: Straylight, contrast sensitivity, astigmatism, uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), and visual symptom score. Results: Straylight at 12 months was 1.37 ± 0.2 logarithm of straylight for FS DSEK and 1.46 ± 0.2 logarithm of straylight for PK (P =.151). During 12 months of follow-up, there was a significant improvement of straylight and contrast sensitivity after FS DSEK (P <.001) and PK (P <.001). The change of straylight and contrast sensitivity correlated significantly with the change of BSCVA after FS DSEK (r = -0.645; r = 0.580) and PK (r = -0.370; r = 0.659). The visual symptom score was comparable between the 2 groups during the 12 months of follow-up. Conclusions: Improvement of straylight and contrast sensitivity was significantly correlated with an improvement of BSCVA. Straylight and contrast sensitivity were improved significantly after FS DSEK and were comparable with those after PK, although BSCVA was slightly better in the PK group. © 2011 Elsevier Inc.
De Haan J.,Westfriesgasthuis |
Schep N.W.L.,Rotterdam University |
Tuinebreijer W.E.,Rotterdam University |
Patka P.,Rotterdam University |
Den Hartog D.,Rotterdam University
Archives of Orthopaedic and Trauma Surgery | Year: 2010
Objective: To identify if functional treatment is the best available treatment for simple elbow dislocations. Search strategy Electronic databases MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials. Selection criteria Studies were eligible for inclusion if they were trials comparing different techniques for the treatment of simple elbow dislocations. Data analysis Results: were expressed as relative risk for dichotomous outcomes and weighted mean difference for continuous outcomes with 95% confidence intervals. Main results This review has included data from two trials and three observational comparative studies. Important data were missing from three observational comparative studies and the results from these studies were extracted for this review. No difference was found between surgical treatment of the collateral ligaments and plaster immobilisation of the elbow joint. Better range of movement, less pain, better functional scores, shorter disability and shorter treatment time were seen after functional treatment versus plaster immobilisation. © 2009 Springer-Verlag.
Petzold A.,VU University Amsterdam |
Petzold A.,University College London |
Steenwijk M.D.,VU University Amsterdam |
Eikelenboom J.M.,Westfriesgasthuis |
And 2 more authors.
Multiple Sclerosis | Year: 2016
Background: Body fluid and structural imaging biomarkers give information on neurodegeneration. The relationship over time is not known in multiple sclerosis. Objective: To investigate the temporal relationship of elevated cerebrospinal fluid (CSF) neurofilament (Nf) protein levels, a biomarker for axonal loss, with magnetic resonance imaging (MRI) atrophy measures. Methods: In patients with multiple sclerosis, CSF Nf heavy chain (NfH) phosphoform levels were quantified at baseline and dichotomised into 'normal' and 'high'. Atrophy was assessed by MRI at baseline and 15-year follow-up using SIENAX and FreeSurfer software. Results: High baseline CSF NfHSMI35 levels predicted pronounced atrophy at 15-year follow-up (odds ratio (OR): 36, p < 0.01), in the absence of baseline brain atrophy (OR: 28, p < 0.05), for the averaged MRI normalised brain volume (1.44 L vs 1.33 L, p < 0.05), normalised grey matter volume (0.77 L vs 0.69 L, p < 0.01) and putamen (12.7 mL vs 10.7 mL, p < 0.05). Region-specific calculations including the spinal cord showed that a power of >80% is reached with 14-50 patients. Conclusion: These data suggest that high CSF NfH levels are an early predictor of later brain and spinal cord atrophy using structural imaging biomarkers and can be investigated in reasonably sized patient cohorts. © SAGE Publications.
Huitema G.C.,Westfriesgasthuis |
Jansen R.C.,Maastricht University |
Van Ooij A.,Viecuri |
Punt I.M.,Maastricht University |
Van Rhijn L.W.,Maastricht University
Spine Journal | Year: 2015
Background context: According to the Lenke classification, a Type 5 adolescent idiopathic scoliosis can be surgically treated with selective anterior thoracolumbar or lumbar fusion. Purpose: This study aims to predict the spontaneous correction of the unfused thoracic curve after anterior thoracolumbar fusion and to study whether age is of influence on this predictability. Study design: Retrospective study on a consecutive series of patients. Patient sample: Of a consecutive series of 38 patients with idiopathic thoracolumbar scoliosis, Lenke type 5, 29 patients were included in the study. All patients were treated with anterior spinal fusion and instrumentation. A minimum follow-up of 2 years was available for all patients (mean, 4 years; range, 2-17 years). To investigate the influence of age on the outcome, we divided the group into two subgroups: an adolescent (n=13) and an adult age group (n=16). The mean age in the adolescent group was 17 (range, 13-21 years) and 38 years (range, 22-54 years) in the adult group. Outcome measures: Physiological measures include coronal Cobb angle, apical vertebral translation (AVT) and apical vertebral rotation (AVR), shoulder tilt, trunk shift, L4 tilt, and pelvic tilt. Relative corrections were computed for the thoracolumbar and thoracic curves in each patient using the following formula: (preoperative curve-postoperative curve)/preoperative curve×100 (%). The correlation coefficient between the relative (%) corrections of the thoracic and thoracolumbar curves was calculated for the whole group as for the two age subgroups. Methods: For radiographic evaluation, we used standing anteroposterior and lateral projections of the thoracolumbar spine to determine Cobb angle, AVT and AVR, and coronal balance. Results: Both the thoracolumbar and thoracic curves in the whole group improved after surgery (45% and 19%, respectively, p<.01). In the adolescent age group, a significant correlation between the relative (%) correction of the thoracolumbar curve and the relative (%) correction of the thoracic curve was found (R=0.704; p=.01) and between age and relative (%) correction of the thoracic curve (R=-0.805; p<.01). Conclusions: These results show that the spontaneous correction of the thoracic curve is a reflection of the thoracolumbar curve correction in adolescent thoracolumbar idiopathic scoliosis. Moreover, the predictability of the thoracic curve correction in the individual patient seems to decrease with increasing age of the patient. © 2015 Elsevier Inc. All rights reserved.
Iordens G.I.T.,Rotterdam University |
Den Hartog D.,Rotterdam University |
Van Lieshout E.M.M.,Rotterdam University |
Tuinebreijer W.E.,Rotterdam University |
And 4 more authors.
Clinical Orthopaedics and Related Research | Year: 2015
Background: After a complex dislocation, some elbows remain unstable after closed reduction or fracture treatment. Function after treatment with a hinged external fixator theoretically allows collateral ligaments to heal without surgical reconstruction. However, there is a lack of prospective studies that assess functional outcome, pain, and ROM. Questions/purposes: We asked: (1) In complex elbow fracture-dislocations, does treatment with a hinged external fixator result in reduction of disability and pain, and in improvement in ROM, function, and quality of life? (2) Does delayed treatment (7 days or later) have a negative effect on ROM after 1 year? (3) What are the complications seen after external fixator treatment? Methods: During a 2-year period, 11 centers recruited 27 patients 18 years or older who were included and evaluated at 2 and 6 weeks and at 3, 6, and 12 months after surgery as part of this prospective case series. During the study period, the participating centers agreed on general indications for use of the hinged external fixator, which included persistent instability after closed reduction alone or closed reduction combined with surgical treatment of associated fracture(s), when indicated. Functional outcome was evaluated using the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH; primary outcome) score, the Mayo Elbow Performance Index (MEPI), the Oxford Elbow Score, and the level of pain (VAS). ROM, adverse events, secondary interventions, and radiographs also were evaluated. A total of 26 of the 27 patients (96%) were available for followup at 1 year. Results: All functional and pain scores improved. The median QuickDASH score decreased from 30 (25th–75th percentiles [P25–P75], 23–40) at 6 weeks to 7 (P25–P75, 2–12) at 1 year with a median difference of −25 (p < 0.001). The median MEPI score increased from 80 (P25–P75, 64–85) at 6 weeks to 100 (P25–P75, 85–100) at 1 year with a median difference of 15 (p < 0.001). The median Oxford Elbow Score increased from 60 (P25–P75, 44–68) at 6 weeks to 90 (P25–P75, 73–96) at 1 year with a median difference of 29 (p < 0.001). The median VAS decreased from 2.8 (P25–P75, 1.0–5.0) at 2 weeks to 0.5 (P25–P75, 0.0–1.9) at 1 year with a median difference of −2.1 (p = 0.001). ROM also improved. The median flexion-extension arc improved from 50° (P25–P75, 33°–80°) at 2 weeks to 118° (P25–P75, 105°–138°) at 1 year with a median difference of 63° (p < 0.001). Similarly, the median pronation-supination arc improved from 90° (P25–P75, 63°–124°) to 160° (P25–P75, 138°–170°) with a median difference of 75° (p < 0.001). At 1 year, the median residual deficit compared with the uninjured side was 30° (P25–P75, 5°–35°) for the flexion-extension arc, and 3° (P25–P75, 0°–25°) for the pronation-supination arc. Ten patients (37%) experienced a fixator-related complication, and seven patients required secondary surgery (26%). One patient reported recurrent instability. Conclusions: A hinged external elbow fixator provides enough stability to start early mobilization after an acute complex elbow dislocation and residual instability. This was reflected in good functional outcome scores and only slight disability despite a relatively high complication rate. Level of Evidence: Level IV, therapeutic study. © 2014, The Association of Bone and Joint Surgeons®.
Van Den Ham L.H.,Rijnstate Hospital |
Wiersema A.M.,Westfriesgasthuis |
Kievit J.K.,Westfriesgasthuis |
Reijnen M.M.P.J.,Rijnstate Hospital
Journal of Endovascular Therapy | Year: 2016
Purpose: To describe the successful endovascular treatment of 2 patients with type IIIb endoleak using the Nellix EndoVascular Aneurysm Sealing (EVAS) System. Case Report: Two men aged 75 and 83 years presented with type IIIb endoleak several years (8 and 3, respectively) after initial endovascular aneurysm repair. Dual Nellix endoprosthesis were deployed in the stent-grafts, and the endobags were filled with polymer to seal the defect and eliminate the endoleak. The perioperative periods were uneventful. At up to 6-month follow-up, no endoleaks were detected, aneurysm diameters were unchanged, and the endografts were patent. One patient died 7 months after revision due to a metastatic malignancy. Conclusion: The Nellix EVAS System may prove useful for the treatment of type IIIb endoleak. © The Author(s) 2015.
van Drie C.E.,Westfriesgasthuis
Nederlands tijdschrift voor geneeskunde | Year: 2013
A 47-year-old man presented to the emergency department with a rapidly progressive, generalized rash and pustulosis shortly after he had started amoxicillin/clavulanic acid for the treatment of a pulmonary infection. Based on the patient's history and the clinical symptoms, the diagnosis of 'acute generalized exanthematous pustulosis' (AGEP) was suspected. This was confirmed by histopathological examination. The skin abnormalities slowly disappeared after terminating antibiotic medication.