study protocol for a randomized controlled trial

Background Osteoarthritis (OA) is a heterogeneous group of conditions with disturbed integrity of articular cartilage and changes in the underlying bone. The pathogenesis of OA is multifactorial and not just a disease of older people. Hydroxychloroquine (HCQ) is a disease-modifying anti-rheumatic drug (DMARD) typically used for the treatment of various rheumatic and dermatologic diseases. Three studies of HCQ in OA, including one abstract and one letter, are available and use a wide variety of outcome measures in small patient populations. Despite initial evidence for good efficacy of HCQ, there has been no randomized, double-blind, and placebo-controlled trial in a larger patient group. In the European League Against Rheumatism (EULAR), evidence-based recommendations for the management of hand OA, HCQ was not included as a therapeutic option because of the current lack of randomized clinical trials. Methods/Design OA TREAT is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial. A total of 510 subjects with inflammatory and erosive hand OA, according to the classification criteria of the American College of Rheumatology (ACR), with recent X-ray will be recruited across outpatient sites, hospitals and universities in Germany. Patients are randomized 1:1 to active treatment (HCQ 200 to 400 mg per day) or placebo for 52 weeks. Both groups receive standard therapy (non-steroidal anti-inflammatory drugs [NSAID], coxibs) for OA treatment, taken steadily two weeks before enrollment and continued further afterwards. If disease activity increases, the dose of NSAID/coxibs can be increased according to the drug recommendation. The co-primary clinical endpoints are the changes in Australian-Canadian OA Index (AUSCAN, German version) dimensions for pain and hand disability at week 52. The co-primary radiographic endpoint is the radiographic progression from baseline to week 52. A multiple endpoint test and analysis of covariance will be used to compare changes between groups. All analyses will be conducted on an intention-to-treat basis. Discussion The OA TREAT trial will examine the clinical and radiological efficacy and safety of HCQ as a treatment option for inflammatory and erosive OA over 12 months. OA TREAT focuses on erosive hand OA in contrast to other current studies on symptomatic hand OA, for example, HERO [Trials 14:64, 2013]

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)

Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies

Dogs Leaving the ICU Carry a Very Large Multi-Drug Resistant Enterococcal Population with Capacity for Biofilm Formation and Horizontal Gene Transfer

The enterococcal community from feces of seven dogs treated with antibiotics for 2–9 days in the veterinary intensive care unit (ICU) was characterized. Both, culture-based approach and culture-independent 16S rDNA amplicon 454 pyrosequencing, revealed an abnormally large enterococcal community: 1.4±0.8×108 CFU gram−1 of feces and 48.9±11.5% of the total 16,228 sequences, respectively. The diversity of the overall microbial community was very low which likely reflects a high selective antibiotic pressure. The enterococcal diversity based on 210 isolates was also low as represented by Enterococcus faecium (54.6%) and Enterococcus faecalis (45.4%). E. faecium was frequently resistant to enrofloxacin (97.3%), ampicillin (96.5%), tetracycline (84.1%), doxycycline (60.2%), erythromycin (53.1%), gentamicin (48.7%), streptomycin (42.5%), and nitrofurantoin (26.5%). In E. faecalis, resistance was common to tetracycline (59.6%), erythromycin (56.4%), doxycycline (53.2%), and enrofloxacin (31.9%). No resistance was detected to vancomycin, tigecycline, linezolid, and quinupristin/dalfopristin in either species. Many isolates carried virulence traits including gelatinase, aggregation substance, cytolysin, and enterococcal surface protein. All E. faecalis strains were biofilm formers in vitro and this phenotype correlated with the presence of gelE and/or esp. In vitro intra-species conjugation assays demonstrated that E. faecium were capable of transferring tetracycline, doxycycline, streptomycin, gentamicin, and erythromycin resistance traits to human clinical strains. Multi-locus variable number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE) of E. faecium strains showed very low genotypic diversity. Interestingly, three E. faecium clones were shared among four dogs suggesting their nosocomial origin. Furthermore, multi-locus sequence typing (MLST) of nine representative MLVA types revealed that six sequence types (STs) originating from five dogs were identical or closely related to STs of human clinical isolates and isolates from hospital outbreaks. It is recommended to restrict close physical contact between pets released from the ICU and their owners to avoid potential health risks

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Large Housing Estates: Ideas, Rise, Fall and Recovery:

Large housing estates: for some people these three words symbolise all that is wrong in urban planning. Large is wrong, because many people prefer a living surrounding that reflects the human scale. Housing as a single function is wrong, because mixed areas are livelier. And estates are wrong, as these refer to top-down planned areas which the residents themselves have no say in. Although many such estates function well, others have proved to be in serious problems. The question is how to deal with this legacy. For these estates to recover, an integrated solution is needed. Large-scale problems require large-scale interventions. The Amsterdam Bijlmermeer area has been the most deprived and stigmatised area in the Netherlands for at least a quarter of a century, despite its glorious design in the 1960s. The Bijlmermeer can now be considered as a leading case for area regeneration. The author has followed this fascinating neighbourhood for years and provides an analysis of its construction, fall and recovery. Moreover, he compares the Bijlmermeer with many other large housing estates in the Netherlands and abroad, and analyses what conclusions may be of use for other areas. &nbsp

Comment aborder le problème de la délinquance et du vandalisme dans les cités construites après-guerre. L'expérience hollandaise

Im Zusammenhang mit einer niederlandischen Politik zur Vorbeugung von Vandalismus, Kriminalitat und Unsicherheit in den Nachkriegsvierteln untersuchen die Autoren das Zusammenwirken von verschiedenen Faktoren, die zur Verwahrlosung des gebauten Raumes führen und sehen mögliche Massnahmen vor, um gegen das Problem anzugeben. Ein Beispiel von Vorbeugungsmassnahmen wird vorgestellt: die Einstellung von Wachen, kombiniert mit räumlichen Veränderungen einer Siedlung, die von Vandalismus und Kleinkriminalität heimgesucht wird. Eine Auswertung dieser Massnahmen zeigt positive Ergebnisse iiber die Sicherheit der Bewohner und über das Niveau der Kriminalstatistiken, inbesondere im Bereich der Einbriiche. Schlussfolgerend bestehen die Autoren auf der notwendigen Kombination verschiedener Arten von Massnahmen, technischer wie sozialer Art.In the context of the new dutch policy of prevention of vandalism, petty crime and insecurity in post-war housing estates, the authors examine how a combination of various factors lead to a process of decay of the built environment; they consider possible measures to combat the problem. An example of prevention measures is presented : the appointment of caretakers combined with some redesign of public and semi-public spaces, in a vandalism-and-petty- crime-ridden housing estate. Evaluation research shows positive results on feeling of security among residents, as well as on the level of police statistics which decreased, especially with respect to burglary. The authors conclude by emphasizing the necessary interweaving of different types of measures, both of technical and social nature.Dans le cadre d'une politique nouvelle de prévention du vandalisme, de la délinquance et de l'insécurité dans des quartiers construits après-guerre aux Pays-Bas, les auteurs étudient l'imbrication des divers facteurs de dégradation du cadre bâti et envisagent les mesures possibles pour les combattre. Un exemple de mesures de prévention est présenté: il s'agit de l'embauche de gardiens, combinée à des aménagements de l'espace dans une cité subissant vandalisme et petite délinquance. Une recherche evaluative sur ces mesures montre des résultats positifs sur le sentiment de sécurité des habitants et sur le niveau des statistiques policières, notamment en matière de cambriolage. Les auteurs concluent en insistant sur la nécessaire combinaison des différents types de mesures, d'ordre technique comme d'ordre social.In het kader van een nieuw preventiebeleid ten aanzien van vandalisme, van criminaliteit en van onveiligheid in de sociale wijken die opgetrokken werden in de na-oorlogse période in Nederland, bestuderen de auteurs de verschillende faktoren van de degradatie van deze bouwcomplexen en schuiven zij bepaalde oplossingsmodellen naar voor. Een voorbeeld van een preventieve maatregel is, volgens deze auteurs, het aanwerven van bewakers in samenhang met het ver- fraaien van de ruimtelijke ordening in een stad te kampen heeft met vandalisme en kleine criminaliteit. Uit onderzoek is gebleken dat dergelijke preventieve maatregelen positieve resultaten meebrengen. Zowel het gevoel van onveiligheid bij de bewoners nam af als de politiële statistieken in verband met inbraak. De auteurs dringen dan ook aan op het aanwenden van beide preventieve maatregelen in combinatie, zowel van technische en als van sociale aard.Elsinga Marja, Wassenberg Frank. Comment aborder le problème de la délinquance et du vandalisme dans les cités construites après-guerre. L'expérience hollandaise. In: Déviance et société. 1991 - Vol. 15 - N°3. pp. 339-352

Chapitre II. L’exception néerlandaise

Aux Pays-Bas, fait unique en Europe, le marché du logement est dominé par un secteur locatif social très conséquent, qui comptait 2,4 millions de logements en 2005 soit 35 % d’un parc total de 6,8 millions, ou encore un tiers des ménages (chiffre resté stable durant la dernière décennie). Le secteur locatif privé représentait quant à lui 11 % des résidences principales à cette date. Un peu plus de la moitié des ménages (54 %) sont propriétaires-occupants. On voit donc que c’est à un bailleur ..