Risk management of water systems in residential homes : The ‘process’ of Legionella prevention

In the present study data was collect and analysed to gain evidence for the present situation of Legionella risk management and prevention of water systems in different buildings in the Canton of Zurich, Switzerland. These buildings comprise retirement homes, care homes and dwellings for people with a disability. According to given legislation, standards and technical rules, duty holders are liable for the quality of drinking water distributed by the water system in a building. Showers represent a frequently used, aerosol-generating device in the domestic setting and have been proposed as a source of Legionnaires’ disease, caused by Legionella bacteria. This study investigated the prevalence of Legionella in showers which are recognised as a potential source of risk of contamination for users. During a field campaign, data from ten buildings were collected. Water was sampled from showers and analysed with reproducible sampling procedures. As a second source of data, information concerning technical specifications and operating parameters of the (hot) water systems and shower facilities was collected from the operating manager through a semi-structured questionnaire. Based on the microbiological results provided by the classical culture method, a Legionella contamination was detected in two objects. Three additional care facilities showed raised results according to a different method applied. Evaluation of the responses given in the questionnaire revealed that control functions and documentation seem to be either unsatisfactory within the institutions, or are missing completely. Although the small size of the sample in this study does not permit generalizable statements, the results provide a solid foundation upon which further investigations can be based

Long-term effects of caloric restriction or exercise on DNA and RNA oxidation levels in white blood cells and urine in humans

Excessive adiposity is associated with increased oxidative stress and accelerated aging. Weight loss induced by negative energy balance reduces markers of oxidation in experimental animals and humans. The long-term effects of weight loss induced by calorie restriction or increased energy expenditure induced by exercise on measures of oxidative stress and damage have not been studied in humans. The objective of the present study was to compare the effects of 20% caloric restriction or 20% exercise alone over 1 year on oxidative damage to DNA and RNA, as assessed through white blood cell and urine analyses. Eighteen men and women aged 50 to 60 years with a body mass index (BMI) between 23.5 to 29.9 kg/m(2) were assigned to one of two conditions — 20% CR (n = 9) or 20% EX (n = 9) — which was designed to produce an identical energy deficit through increased energy expenditure. Compared to baseline, both interventions significantly reduced oxidative damage to both DNA (48.5% and 49.6% reduction for the CR and EX groups, respectively) and RNA (35.7% and 52.1% reduction for the CR and EX groups, respectively) measured in white blood cells. However, urinary levels of DNA and RNA oxidation products did not differ from baseline values following either 12-month intervention program. Data from the present study provide evidence that negative energy balances induced through either CR or EX result in substantial and similar improvements in markers of DNA and RNA damage to white blood cells, potentially by reducing systemic oxidative stress

International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients

Objectives. The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries. Methods. We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes. Results. Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever. Conclusion. We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be propose

Registries in rheumatological and musculoskeletal conditions. Paediatric Behçet's disease: an international cohort study of 110 patients. One-year follow-up data

Objective. To set-up an international cohort of patients suspected with Behçet's disease (BD). The cohort is aimed at defining an algorithm for definition of the disease in children. Methods. International experts have defined the inclusion criteria as follows: recurrent oral aphthosis (ROA) plus one of following—genital ulceration, erythema nodosum, folliculitis, pustulous/acneiform lesions, positive pathergy test, uveitis, venous/arterial thrombosis and family history of BD. Onset of disease is <16 years, disease duration is ≤3 years, future follow-up duration is ≥4 years and informed consent is obtained. The expert committee has classified the included patients into: definite paediatric BD (PED-BD), probable PED-BD and no PED-BD. Statistical analysis is performed to compare the three groups of patients. Centres document their patients into a single database. Results. At January 2010, 110 patients (56 males/54 females) have been included. Mean age at first symptom: 8.1 years (median 8.2 years). At inclusion, 38% had only one symptom associated with ROA, 31% had two and 31% had three or more symptoms. A total of 106 first evaluations have been done. Seventeen patients underwent the first-year evaluation, and 36 had no new symptoms, 12 had one and 9 had two. Experts have examined 48 files and classified 30 as definite and 18 as probable. Twenty-six patients classified as definite fulfilled the International Study Group criteria. Seventeen patients classified as probable did not meet the international criteria. Conclusion. The expert committee has classified the majority of patients in the BD group although they presented with few symptoms independently of BD classification criteri

The multifaceted presentation of chronic recurrent multifocal osteomyelitis: A series of 486 cases from the Eurofever international registry

Objectives. Chronic non-bacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder characterized by sterile bone osteolytic lesions. The aim of this study was to evaluate the demographic data and clinical, instrumental and therapeutic features at baseline in a large series of CNO/CRMO patients enrolled in the Eurofever registry. Methods. A web-based registry collected retrospective data on patients affected by CRMO/CNO. Both paediatric and adult centres were involved. Results. Complete baseline information on 486 patients was available (176 male, 310 female). The mean age of onset was 9.9 years. Adult onset (>18 years of age) was observed in 31 (6.3%) patients. The mean time from disease onset to final diagnosis was 1 year (range 0-15). MRI was performed at baseline in 426 patients (88%), revealing a mean number of 4.1 lesions. More frequent manifestations not directly related to bone involvement were myalgia (12%), mucocutaneous manifestations (5% acne, 5% palmoplantar pustulosis, 4% psoriasis, 3% papulopustular lesions, 2% urticarial rash) and gastrointestinal symptoms (8%). A total of 361 patients have been treated with NSAIDs, 112 with glucocorticoids, 61 with bisphosphonates, 58 with MTX, 47 with SSZ, 26 with anti-TNF and 4 with anakinra, with a variable response. Conclusion. This is the largest reported case series of CNO patients, showing that the range of associated clinical manifestations is rather heterogeneous. The study confirms that the disease usually presents with an early teenage onset, but it may also occur in adults, even in the absence of mucocutaneous manifestations

Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas

Most genome-wide association studies (GWAS) were analyzed using single marker tests in combination with stringent correction procedures for multiple testing. Thus, a substantial proportion of associated single nucleotide polymorphisms (SNPs) remained undetected and may account for missing heritability in complex traits. Model selection procedures present a powerful alternative to identify associated SNPs in high-dimensional settings. In this GWAS including 1060 colorectal cancer cases, 689 cases of advanced colorectal adenomas and 4367 controls we pursued a dual approach to investigate genome-wide associations with disease risk applying both, single marker analysis and model selection based on the modified Bayesian information criterion, mBIC2, implemented in the software package MOSGWA. For different case-control comparisons, we report models including between 1-14 candidate SNPs. A genome-wide significant association of rs17659990 (P=5.43x10(-9), DOCK3, chromosome 3p21.2) with colorectal cancer risk was observed. Furthermore, 56 SNPs known to influence susceptibility to colorectal cancer and advanced adenoma were tested in a hypothesis-driven approach and several of them were found to be relevant in our Austrian cohort. After correction for multiple testing (alpha=8.9x10(-4)), the most significant associations were observed for SNPs rs10505477 (P=6.08x10(-4)) and rs6983267 (P=7.35x10(-4)) of CASC8, rs3802842 (P=8.98x10(-5), COLCA1,2), and rs12953717 (P=4.64x10(-4), SMAD7). All previously unreported SNPs demand replication in additional samples. Reanalysis of existing GWAS datasets using model selection as tool to detect SNPs associated with a complex trait may present a promising resource to identify further genetic risk variants not only for colorectal cancer

The multifaceted presentation of chronic recurrent multifocal osteomyelitis: a series of 486 cases from the Eurofever international registry

Objectives: Chronic non-bacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder characterized by sterile bone osteolytic lesions. The aim of this study was to evaluate the demographic data and clinical, instrumental and therapeutic features at baseline in a large series of CNO/CRMO patients enrolled in the Eurofever registry. Methods: A web-based registry collected retrospective data on patients affected by CRMO/CNO. Both paediatric and adult centres were involved. Results: Complete baseline information on 486 patients was available (176 male, 310 female). The mean age of onset was 9.9 years. Adult onset (>18 years of age) was observed in 31 (6.3%) patients. The mean time from disease onset to final diagnosis was 1 year (range 0-15). MRI was performed at baseline in 426 patients (88%), revealing a mean number of 4.1 lesions. More frequent manifestations not directly related to bone involvement were myalgia (12%), mucocutaneous manifestations (5% acne, 5% palmoplantar pustulosis, 4% psoriasis, 3% papulopustular lesions, 2% urticarial rash) and gastrointestinal symptoms (8%). A total of 361 patients have been treated with NSAIDs, 112 with glucocorticoids, 61 with bisphosphonates, 58 with MTX, 47 with SSZ, 26 with anti-TNF and 4 with anakinra, with a variable response. Conclusion: This is the largest reported case series of CNO patients, showing that the range of associated clinical manifestations is rather heterogeneous. The study confirms that the disease usually presents with an early teenage onset, but it may also occur in adults, even in the absence of mucocutaneous manifestations

International cohort study for pediatric Behçet’s Disease: update 2011

PubMe

OP0164 LONG-TERM SAFETY OF ANAKINRA IN PATIENTS WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS FROM THE PHARMACHILD REGISTRY

Background:Systemic juvenile idiopathic arthritis (SJIA) is characterized by extra-articular manifestations, as fever and rash, and rarely associated by a potentially lethal complication as macrophage activation syndrome (MAS). Anakinra is a recombinant human interleukin (IL)-1 receptor antagonist whose efficacy and safety profile has been studied for patients with SJIA.Objectives:To evaluate the long-term safety profile of anakinra in patients with SJIA.Methods:Data from patients with SJIA enrolled in the Pharmachild registry before 30 September 2018 and treated with anakinra were analyzed. The study endpoints were the occurrence of non-serious adverse events (AEs) of at least moderate severity and serious AEs (SAEs), including macrophage activation syndrome (MAS), and the duration of anakinra treatment with reasons for discontinuation. All endpoints were analyzed overall, by 6 month-time windows and in different treatment sets represented by those patients continuously treated with anakinra for at least 12, 18 and 24 months (set-12, -18, -24, respectively).Results:306 patients were enrolled. 46%, 34% and 28% of them had been treated for at least 12, 18 and 24 months, respectively. 201 AEs, mostly represented by infections, were reported for 509.3 patient-years (py) with an overall incidence rate (IR) of 39.5/100 py. Among 56 SAEs (IR 11.0/100 py), (Table 1) 23.2% were infections and 19.6% MAS episodes. The IR of AEs was higher during the first 6 months of anakinra, followed by decreasing IR in the different long-term treatment sets. Treatment discontinuation occurred in 76% of patients, most in the first 6 months, due to inefficacy (43%), remission (31%) or AEs/intolerance (15%). No deaths or malignancies occurred during anakinra treatment.Table 1.Number of SAEs and incidence rates (95% CI) by overall PT decreasing order and time window in the complete set (events with a frequency >1 by overall SOC and >1 by overall PT were reported) Only time windows 10.000 USD each) from the following industries in the last 3 years: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties