Orphanet J Rare Dis
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Orphanet J Rare Dis · Jan 2020
Multicenter StudyManagement and current status of spinal muscular atrophy: a retrospective multicentre claims database analysis.
The interest in patient demographics and disease management has increased in the past years due to their utility in developing measures that allow healthcare providers to reflect disease complexity. ⋯ Patients exhibited similar characteristics to prior European studies. Multiple admissions in younger patients, mostly due to respiratory issues, have a central role in increasing medical costs of SMA. Equally, the higher risk of patients and increased number of multimorbidity groups translate in an elevated number of admissions in health centres and ER, deriving in higher expenses.
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Orphanet J Rare Dis · Dec 2014
Multicenter StudySeverity score for hereditary hemorrhagic telangiectasia.
A disease severity score in hereditary hemorrhagic telangiectasia (HHT) would be a useful tool for assessing burden of disease and for designing clinical trials. Here, we propose the first known HHT severity score, the HHT-score. ⋯ We have taken the first steps toward creating a global measure of disease severity in HHT. While the initial results are promising, further validation of the HHT-score is still required.
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Orphanet J Rare Dis · Jan 2014
Multicenter StudyRenal cell tumour characteristics in patients with the Birt-Hogg-Dubé cancer susceptibility syndrome: a retrospective, multicentre study.
The Birt-Hogg-Dubé syndrome is a rare cancer susceptibility syndrome characterised by renal tumours, lung cysts and pneumothoraces, and fibrofolliculomas. It is caused by dominantly inherited mutations in FLCN. Our objective was to report renal tumour characteristics in a large series of patients with the Birt-Hogg-Dubé syndrome. ⋯ Age at renal tumour diagnosis was highly variable, highlighting the need for regular surveillance from young adulthood to old age. Most cases had tumour types classically associated with Birt-Hogg-Dubé, i.e. oncocytoma or renal cell carcinoma of the chromophobe or hybrid type. Nevertheless, 9% had clear cell renal cell carcinoma. Geneticists, urologists and oncologists should therefore be alert to the possibility of Birt-Hogg-Dubé in patients with renal cell carcinoma of clear cell histology, especially if there are associated manifestations. Finally, the behaviour of metastatic carcinoma seemed more indolent than in sporadic renal cancers.
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Orphanet J Rare Dis · Jan 2014
Multicenter StudyFunctional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study.
Malignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1). To identify factors explaining the variable phenotypic presentation and complex pathomechanism, we analyzed proven MH events in terms of clinical course, muscle contracture, genetic factors and pharmocological triggers. ⋯ An MH event could depend on patient-related risk factors such as male gender, young age and causative RyR1 mutations as well as on the use of drugs lowering the threshold of myoplasmic Ca2+ release. SCh might act as an accelerant by promoting unspecific Ca2+ influx via the sarcolemma and indirect RyR1 activation. Most MH crises develop in response to the combined administration of SCh and volatile anesthetics.
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Orphanet J Rare Dis · Jan 2013
Randomized Controlled Trial Multicenter StudyUrsodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial.
Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of cardiovascular events and alternatives need to be explored. Preclinical studies suggest that the combination of celecoxib with ursodeoxycholic acid (UDCA) is a potentially effective strategy. We performed a randomized, double-blind, placebo-controlled trial to investigate the effect of celecoxib and UDCA co-treatment on duodenal adenomatosis in patients with FAP. ⋯ Celecoxib reduces duodenal polyp density in patients with FAP, and unexpectedly, high dose UDCA co-treatment counteracts this effect. The benefit of long term use of celecoxib for duodenal cancer prevention needs to be weighed against the (risk of) adverse events.