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Hoofddorp, Netherlands

Weijerman M.E.,VU University Amsterdam | De Winter J.P.,Spaarne Hospital
European Journal of Pediatrics | Year: 2010

Down syndrome (DS) is one of the most common chromosomal abnormalities. Because of medical advances and improvements in overall medical care, the median survival of individuals with DS has increased considerably. This longer life expectancy requires giving the necessary care to the individual with DS over their total longer lifespan. DS medical guidelines are designed for the optimal care of the child in whom a diagnosis of DS has been confirmed. We present an overview of the most important issues related to children with DS based on the most relevant literature currently available. © 2010 The Author(s).

Pollak M.N.,McGill University | Beeker A.,Spaarne Hospital
The Lancet Oncology | Year: 2015

Background: In preclinical work and retrospective population studies, the anti-diabetic drug metformin has been associated with antineoplastic activity and decreased burden of many cancers, including pancreatic cancer. There is therefore interest in the hypothesis that this drug might be repurposed for indications in oncology. We aimed to assess the efficacy of the addition of metformin to a standard systemic therapy in patients with advanced pancreatic cancer, and provide the first report of a clinical trial with a survival endpoint of metformin for an oncological indication. Methods: We did this double-blind, randomised, placebo-controlled phase 2 trial at four centres in the Netherlands. Patients aged 18 years or older with advanced pancreatic cancer were randomly assigned (1:1), via a permutated computer-generated block allocation scheme (block size of six) to receive intravenous gemcitabine (1000 mg/m2) on days 1, 8, and 15 every 4 weeks and oral erlotinib (100mg) once daily in combination with either oral metformin or placebo twice daily. Metformin dose was escalated from 500 mg (in the first week) to 1000 mg twice daily in the second week. Randomisation was stratified by hospital, diabetes status, and tumour stage. The primary endpoint was overall survival at 6 months in the intention-to-treat population. This trial is complete and is registered with ClinicalTrials.gov, number NCT01210911. Findings: Between May 31, 2010, and Jan 3, 2014, we randomly assigned 121 patients to receive gemcitabine and erlotinib with either placebo (n=61) or metformin (n=60). Overall survival at 6 months was 63·9% (95% CI 51·9-75·9) in the placebo group and 56·7% (44·1-69·2) in the metformin group (p=0·41). There was no difference in overall survival between groups (median 7·6 months [95% CI 6·1-9·1] vs 6·8 months [95% CI 5·1-8·5] in the metformin group; hazard ratio [HR] 1·056 [95% CI 0·72-1·55]; log-rank p=0·78). The most frequent grade 3-4 toxic effects were neutropenia (15 [25%] patients in placebo group vs 15 [25%] in metformin group), skin rash (six [10%] vs four [7%]), diarrhoea (three [5%] vs six [10%]), and fatigue (two [3%] vs six [10%]). Interpretation: Addition of a conventional anti-diabetic dose of metformin does not improve outcome in patients with advanced pancreatic cancer treated with gemcitabine and erlotinib. Future research should include studies of more potent biguanides, and should focus on patients with hyperinsulinaemia and patients with tumours showing markers of sensitivity to energetic stress, such as loss of function of AMP kinase, a key regulator of cellular energy homoeostasis. Funding: Academic Medical Centre, Amsterdam, and The Terry Fox Foundation, Vancouver, Canada. © 2015 Elsevier Ltd.

Hughes J.M.B.,Imperial College London | Van Der Lee I.,Spaarne Hospital
European Respiratory Journal | Year: 2013

The transfer factor of the lung for nitric oxide (TL,NO) is a new test for pulmonary gas exchange. The procedure is similar to the already well-established transfer factor of the lung for carbon monoxide (TL,CO). Physiologically, TL,NO predominantly measures the diffusion pathway from the alveoli to capillary plasma. In the Roughton-Forster equation, T L,NO acts as a surrogate for the membrane diffusing capacity (DM). The red blood cell resistance to carbon monoxide uptake accounts for ̃50% of the total resistance from gas to blood, but it is much less for nitric oxide. TL,NO and TL,CO can be measured simultaneously with the single breath technique, and DM and pulmonary capillary blood volume (V c) can be estimated. TL,NO, unlike TL,CO, is independent of oxygen tension and haematocrit. The TL,NO/T L,CO ratio is weighted towards the DM/Vc ratio and to a; where α is the ratio of physical diffusivities of NO to CO (α=1.97). The TL,NO/TL,CO ratio is increased in heavy smokers, with and without computed tomography evidence of emphysema, and reduced in the voluntary restriction of lung expansion; it is expected to be reduced in chronic heart failure. The TL,NO/TL,CO ratio is a new index of gas exchange that may, more than derivations from them of DM and Vc with their in-built assumptions, give additional insights into pulmonary pathology.

Colen S.,University Hospitals Leuven | Van Den Bekerom M.P.J.,Spaarne Hospital | Mulier M.,University Hospitals Leuven | Haverkamp D.,Slotervaart Hospital
BioDrugs | Year: 2012

Background: Although accepted as a conservative treatment option for knee osteoarthritis, the debate about the effectiveness of intra-articular treatment with hyaluronic acid (HA) is still ongoing because of contrasting outcomes in different clinical studies. Several well designed clinical studies showed a significant improvement in pain at follow-up compared with baseline but no significant improvement comparing the efficacy of HA with placebo (saline) or with other conservative treatment options. Notwithstanding the effectiveness of different types of intra-articular HA products, the question of whether one HA product is better than another is still unanswered. In this systematic review we compare the effects of intra-articularly administered HA with intra-articularly administered placebo in general and, more specifically, the effects of individual HA products with placebo. We also compare the efficacy of different HA products. Methods: Asystematic review of randomized controlled trials (RCTs)was conducted using databases including MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trial Register and EMBASE. Results: Seventy-four RCTs were included in this systematic review. HA improves pain by approximately 40-50%compared with baseline levels. However, when compared with saline the difference in efficacy is not that large. Due to a large 'placebo effect' of saline (approximately 30% pain reduction, persisting for at least 3 months) we determined a weighted mean difference between the efficacy of HA and saline of just 10.20 using the visual analog scale for pain. It is debatable whether this difference reaches the minimum clinically important difference. Comparing the different HA products, which vary in the molecular weight, concentration, and volume of HA, we were not able to conclude that one brand has a better efficacy than another due to the heterogeneity of the studies and outcomes. Discussion: In the future it will be important to determine the exact mechanism of action of placebo as this may give us an idea of how to treat osteoarthritis more efficiently. Due to the limitations of this review (follow-up of just 3 months and large heterogeneity of the included studies), it is also important to compare the different HA products to determine which product(s), or which molecular weight range, concentration, or volume ofHAis the best option to treat osteoarthritis. Our recommendation is to start large (multicenter) RCTs to give us more evidence about the efficacy of the different HA products. © 2012 Springer International Publishing AG. All rights reserved.

Louwerens J.K.G.,Research Center Linnaeus Institute | Veltman E.S.,Spaarne Hospital | Van Noort A.,Spaarne Hospital | Van Den Bekerom M.P.J.,Onze Lieve Vrouwen Gasthuis
Arthroscopy - Journal of Arthroscopic and Related Surgery | Year: 2016

Purpose The objectives of this comprehensive quantitative review of the treatment of calcific tendinopathy of the rotator cuff were to investigate if there is a sustainable positive effect on outcomes after treatment with high-energy extracorporeal shockwave therapy (ESWT) or ultrasound (US)-guided needling and to compare these results with those of treatment with arthroscopic surgery. Methods The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to conduct this review. A systematic literature search was conducted in December 2014 to identify relevant clinical articles in peer-reviewed journals with at least 6 months' follow-up. Each article was scored using the Coleman Methodology Score. The primary endpoints were functional outcome and radiologic change in the size of the calcific deposit. Results Twenty-two studies were included (1,258 shoulders). The mean Coleman Methodology Score for the included studies was 77.1 ± 9.1. Overall, good to excellent clinical outcomes were achieved after treatment with either high-energy ESWT, US-guided needling, or arthroscopic surgery, with an improvement in the Constant-Murley score ranging between 26.3 and 41.5 points after 1 year. No severe side effects or long-term complications were encountered. Conclusions Patients can achieve good to excellent clinical outcomes after high-energy ESWT, US-guided needling, and arthroscopy for calcific tendinopathy of the shoulder. Side effects and post-treatment complications should be taken into account when a decision is being made for each individual patient. Physicians should consider high-energy ESWT and US-guided needling as minimally invasive treatment options when primary conservative treatment fails. Arthroscopy can safely be used as a very effective but more invasive secondary option, although the extent of deposit removal and the additional benefit of subacromial decompression remain unclear. Level of Evidence Level IV, systematic review of Level I, II, and IV studies. © 2016 Arthroscopy Association of North America.

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