Analyses of registry data of patients with anti-GBM and antineutrophil cytoplasmatic antibody-associated (ANCA) vasculitis treated with or without therapeutic apheresis.

Therapeutic apheresis (TA) as a treatment for antibody-associated vasculitis (AAV) was questioned by the PEXIVAS although the MEPEX study favored TA. The aim of this study was to evaluate the efficacy of TA to improve renal function in patients consecutively included in the WAA-apheresis registry versus patients not treated with TA. MATERIALS AND METHODS: Included were 192 patients that suffered from anti-glomerular basement membrane disease (anti-GBM, n = 28) and antineutrophil cytoplasmic antibody-associated vasculitis of MPO or PR3 origin. Of these 119 had performed TA and the other 73 had not performed TA for theses diagnoses (CTRL). RESULTS: Elderly had an increased risk to die within 12 months (p = 0.002). All 28 anti-GBM had renal involvement, 21 dialysis dependent. At 3 month nine (36 %) did not need dialysis. Baseline data regarding renal function of AAV patients, subtype MPO and PR3, were worse in the TA groups than in CTRL. Recovery out of dialysis was better for the PR3-TA group compared with 1) the controls of MEPEX (RR 0.59, CI 0.43-0.80) and 2) the MPO-TA patients (RR 0.28, CI 0.12-0.68). The MPO-TA recovered similarly as the MEPEX-CTRL. Renal function improved most for TA-patients from baseline during the first 3 months (MPO-TA and PR3-TA) and stabilized thereafter and less for MPO-CTRL and PR3-CTRL. CONCLUSION: PR3-TA patients seem to have best chances to get out of dialysis. PR3-TA and MPO-TA improved residual renal function better than CTRL. The present study recommends reconsiderations to use TA for AAV especially those with PR3-vasculitis with severe renal vasculitis.

Analysis of extracorporeal photopheresis within the frame of the WAA register.

The aim of the study was to investigate safety and if extracorporeal photopheresis (ECP) may change health criteria (HC) and quality of life (QoL). MATERIAL AND METHOD: 560 patients (33 % women) were treated with ECP for a total of 13,871 procedures during a 17-years period. Mean age was 48 years (±18, range 3-81 years). Self-estimation of QoL was graded: 0 (suicidal) up to 10 (best ever) and HC: 0 (Bed ridden, ICU condition) up to 10 (athletic). Adverse events were analyzed. ANOVA and paired comparisons were performed. RESULTS: Patients were treated due to graft versus host disease (GVHD, n = 317), skin lymphoma (n = 70), solid organ transplants (n = 47), skin diseases (n = 20) and other diseases (n = 106). Adverse events (AEs) were registered in 5.4 % of the first treatments and in 1.2 % of the subsequent procedures. Severe AEs were present in 0.04 % of all procedures. No patient died due to the procedure. Tingling and stitching were the most common AE. For those with GVHD an improvement was noticed within approximately 10 procedures of ECP in the severity stage, QoL (from a mean of 6.1 to 6.8, p < 0.002) and the HC (6.1 -> 6.4, p < 0.014) and improved further with added procedures. CONCLUSION: Photopheresis is an established therapy with few side effects. The present study of soft variables indicate that GVHD shows benefits upon ECP within approximately 10 procedures in regard to the severity of mainly skin GVHD, and lower baseline levels of HC and QoL.

Evaluation of health and quality of life in apheresis patients - data from the WAA register.

OBJECTIVE: The World Apheresis Association (WAA) register contains data from more than 89 000 apheresis procedures in more than 12,000 patients. The aim of this study was to evaluate functional health and quality of life (QoL) in patients during apheresis treatment. MATERIAL AND METHODS: Estimates of health condition (HC) were made in 40,445 and of QoL in 22112 apheresis procedures. This study focused on a 10-step graded evaluation of HC (scale from: 'bedridden, unable to eat' to a level of 'athletic competition') and self-assessment of QoL (scale from: worst ever '0' to best ever '10'). Data were compared in relation to various apheresis procedures and if the patient underwent the first or subsequent apheresis procedure. RESULTS: Of the patients treated with plasma exchange (PEX) with centrifugation technique (n = 15787) 10% were 'bedridden, unable to come out of bed' while for patients treated with plasma filtration technique (n = 1018) the percentage was 27%. During the first procedure these figures were 16% and 30%, respectively. Self-estimates of QoL were graded 'zero' or '1' in 1.6% of patients during the first apheresis procedure; At the first contact patients undergoing PEX graded like this in 4.3%. CONCLUSION: Many of the patients undergoing apheresis treatment have poor HC and QoL at the start of therapy. Of all therapeutic apheresis procedures patients undergoing PEX had the lowest score of QoL.

Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry.

The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more oncological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years.

Adverse events in apheresis: An update of the WAA registry data.

Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

Age-specific differences in influenza virus type and subtype distribution in the 2012/2013 season in 12 European countries.

The epidemiology of seasonal influenza is influenced by age. During the influenza season, the European Influenza Surveillance Network (EISN) reports weekly virological and syndromic surveillance data [mostly influenza-like illness (ILI)] based on national networks of sentinel primary-care providers. Aggregated numbers by age group are available for ILI, but not linked to the virological data. At the end of the influenza season 2012/2013, all EISN laboratories were invited to submit a subset of their virological data for this season, including information on age. The analysis by age group suggests that the overall distribution of circulating (sub)types may mask substantial differences between age groups. Thus, in cases aged 5-14 years, 75% tested positive for influenza B virus whereas all other age groups had an even distribution of influenza A and B viruses. This means that the intepretation of syndromic surveillance data without age group-specific virological data may be misleading. Surveillance at the European level would benefit from the reporting of age-specific influenza data.

Seroepidemiology of mumps in Europe (1996-2008): why do outbreaks occur in highly vaccinated populations?

Mumps outbreaks have recently been recorded in a number of highly vaccinated populations. We related seroprevalence, epidemiological and vaccination data from 18 European countries participating in The European Sero-Epidemiology Network (ESEN) to their risk of mumps outbreaks in order to inform vaccination strategies. Samples from national population serum banks were collected, tested for mumps IgG antibodies and standardized for international comparisons. A comparative analysis between countries was undertaken using age-specific mumps seroprevalence data and information on reported mumps incidence, vaccine strains, vaccination programmes and vaccine coverage 5-12 years after sera collection. Mean geometric mumps antibody titres were lower in mumps outbreak countries [odds ratio (OR) 0·09, 95% confidence interval (CI) 0·01-0·71)]. MMR1 vaccine coverage ⩾95% remained protective in a multivariable model (P < 0·001), as did an interval of 4-8 years between doses (OR 0·08, 95% CI 0·01-0·85). Preventing outbreaks and controlling mumps probably requires several elements, including high-coverage vaccination programmes with MMR vaccine with 4-8 years between doses.

Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis in sexually intact girls with arthritides.

OBJECTIVES: To investigate the frequency of Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis in the genital tract of sexually intact girls with arthritides, and to search for optimal means of their elucidation. METHOD: Sixty girls with rheumatic arthritides and 61 girls who had applied to a children's gynaecologist because of genital complaints (control group), aged 2-16 years, were examined. First-catch urine and swabs were taken from the vaginal arc and the surface of the external orifice of the urethra. C. trachomatis was elucidated by ligase chain reaction (LCR). U. urealyticum and M. hominis were detected with the Mycoplasma Duo diagnostic kit. RESULTS: One of the investigated microorganisms was found in nine (15%) girls with arthritis: C. trachomatis in one (1.7%), U. urealyticum in six (10%), and M. hominis in two (3.3%). In patients without arthritis, only U. urealyticum was detected in two (3.3%) girls. Nine (15%) girls with arthritis had genital symptoms (actively revealed only through a questionnaire), and in seven of them the investigated microorganisms were elucidated. Taking smears from the external orifice of the urethra failed to elucidate the microorganisms studied in only 1/11 positive cases from both patient groups. CONCLUSIONS: C. trachomatis was found in 1.7%, U. urealyticum in 10%, and M. hominis in 3.3% of 60 sexually intact girls with rheumatic arthritides. Actively detected genital symptoms may serve as a guide for examining girls with arthritis for these rare infections. The external orifice of the urethra may be an alternative easily accessible site for taking material for examination.

Thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). There are many secondary causes of TMA, many of them could mimic TTP or HUS. This article presents a short overview on TMA. In conclusion TMA is the result of various etiology reasons and pathologic reactions with various clinical entities. It is important to focus on a thorough history including family history when deciding on a diagnosis. Analysis of ADAMTS 13 and ADAMTS 13-antibodies may help to decide continued therapy.

Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry.

UNLABELLED: Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients. MATERIALS AND METHODS: Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry. RESULTS: The mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r=-0.47, p=0.034). CONCLUSIONS: Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact on the ADAMTS13 levels.

World apheresis registry data from 2003 to 2007, the pediatric and adolescent side of the registry.

OBJECTIVES: Paediatric patients are a special group in apheresis. It is general accepted to use adult indications in paediatric patients, but data in this age group are rare. In order to provide more information of apheresis practise in children and young adults (<21a) we will report of knowledge learnt by data from the registry from 2003 until 2007. METHODS: This is a web-based registry. A link is available from the WAA homepage (www.worldapheresis.org). So far data from 12,448 procedures have been included. Six hundred and twelve procedures were performed in 135 children and young adults (308 procedures<16a, 237 from 17 to 20a, and 67 with 21a) representing 5% of the total population. The median age was 14 years (range 1-21 years), 74 male and 61 female. These data were entered by 15 centres with a frequency of in median 18 aphereses in young patients per centre (range 1-287) from 2003 to 2007. RESULTS: Main indications: haematological diseases and also nephrological, and neurological. The type of aphereses was mainly Leukapheresis (196, 33%), plasma exchange (149, 25%), photopheresis (127, 21%), and lipid aphereses (79, 13%). Blood access: peripheral vessels in 305 procedures (50%, compared to 73% in adults), central venous catheter in 239 (38%), and AV-fistula in 2% and 0.3%, and in 8 (1.31%) procedures an arterial line was used. Anticoagulation was mostly by ACD (71%), heparin (18% or the combination of both (3%). 39 adverse events (AE) were registered in 22 (=3.59%) of the procedures, mostly graded as mild. Treatment was interrupted in 14 procedures (2.29%). AE's were abdominal pain, anaphylactic shock, flush, hyper- and hypotension, nausea, vertigo, cephalea and need for sedation and technical problems with the device and problems with the venous access. The rate of AE's was similar for stem cell harvesting and for plasma exchange (4% and 4.7%, respectively). CONCLUSION: The paediatric data compared to the whole registry data set are showing that aphereses are performed as safe in paediatrics as in adults. Centres are mostly handling only a few cases younger than 21. Therefore more exchange of information and experience in paediatric apheresis is warranted.

World apheresis registry 2003-2007 data.

OBJECTIVES: Seventy-five centers from many countries have applied for a login code to the WAA apheresis registry. Fifteen centers from 7 countries have been actively entering data at the internet site from 2003 until 2007. We report on data from the registry so far. METHODS: This is a web-based registry. A link is available from the WAA homepage (www.worldapheresis.org). So far data from 2013 patients (12,448 procedures) have been included. A median of 6 treatments have been performed (range 1-140). Mean age 51 years (range 1-94 years; 45% women). Seven percent of the patients were < or = 21 years and 4% were < or = 16 years. RESULTS: The purpose of the apheresis procedure was therapeutic in 67% and retrieval of blood components in 33%. Main indications: neurological and hematological diseases, lipid apheresis and stemcell collection (autologous, and some allogeneic). Blood access: peripheral vessels (71%), central dialysis catheter through jugular (6.5%) or subclavian veins (6.7%), femoral vein (8%) and AV fistula (4%). ACD was used for anticoagulation in 73% of the procedures. Albumin was mainly used as replacement fluid. Adverse events (AE) were registered in 5.7% of the procedures. AE was graded as mild (2.5%), moderate (2.7%) or severe (0.5%). No death occurred due to treatment. The procedures were interrupted in 2.6%. Most frequent AEs were blood access problems (29%), tingling around the mouth (20%), hypotension (18%), and urticaria (9%). There were significant differences between the centers regarding mild and moderate AEs. Data indicate that centers using continuous infusion of calcium had fewer AEs. CONCLUSION: There was a limited number of severe AEs. Centers use various standard procedures for apheresis. By learning from the experience of others the treatment quality will improve further. In the near future, an update of the registry will enable more extensive evaluation of the data.

[The prevalence of viral hepatitides among youth]. / Rasprostranenie virusnykh gepatitov sredi molodezhi.

The study of 632 teenagers has revealed that young people are the main group of risk with respect to the spread of virus hepatitides B and C, HIV infection. In accordance with risk factors, the teenagers have been divided into 4 groups: using drugs by injection; leading sexual life; using drugs and leading sexual life; having no risk factor indicated. The presence of hepatitis B and hepatitis C virus infection has been established in 1.42 and 1.27% of cases respectively. This is due to the frequent change of partners, the use of narcotic drugs since school age, the absence of necessary information and contacts with parents. When considering this problem, mass media have been found to play an important role. The presence of reliable information breaking old stereotypes may help parents pay greater and better attention to the upbringing and health of their children.

The European Sero-Epidemiology Network 2 (ESEN2): standardization of assay results for hepatitis A virus (HAV) to enable comparisons of seroprevalence data across 15 countries.

The European Sero-Epidemiology Network 2 (ESEN2) aimed to compare serological results of vaccine-preventable diseases across Europe. To ensure direct inter-country comparability of hepatitis A virus antibody (anti-HAV) measurements, a standardization panel of 150 sera was developed by a designated reference laboratory and tested by participating national laboratories using assays of choice; each country's results were subsequently regressed against those of the reference laboratory. Quantitatively, the assays were generally highly correlated (R2>0.90). Nevertheless, qualitative comparisons indicated that results obtained with different assays may differ despite the usage of well-established international and local standards. To a great extent standardization successfully alleviated such differences. The generated standardization equations will be used to convert national serological results into common units to enable direct international comparisons of HAV seroprevalence data. The results of this study are expected to contribute to the evaluation and potential improvement of the currently employed immunization strategies for hepatitis in Europe.

The European Sero-Epidemiology Network 2: standardization of assay results for hepatitis B virus.

The aim of the European Sero-Epidemiology Network 2 was to coordinate and standardize the serological surveillance of vaccine-preventable diseases in Europe. In this study, the standardization of hepatitis B virus (HBV) results is described. The 15 participating national laboratories tested a unique panel of 172 sera established by the Greek reference centre for HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs) and/or to the HBV core antigen (anti-HBc) by assay methods of their choice. Country-specific quantitative measurements for anti-HBs and anti-HBc were transformed into common units using standardization equations derived by regressing each country's panel results against the reference centre's results, thus adjusting for interassay and interlaboratory variability. For HBsAg, a qualitative analysis (positive/negative) showed at least 99% agreement with the reference laboratory for all countries. By combining these standardized and qualitative results for the markers mentioned earlier, it was possible to achieve comparable estimates of the proportion of the population susceptible to HBV, vaccinated against HBV, with a past HBV infection, and with a current infection or chronic carrier state. Standardization is a very important tool that allows for international serological comparisons to assess the current vaccination policies and the progress of HBV control in Europe.

Standardization of measles, mumps and rubella assays to enable comparisons of seroprevalence data across 21 European countries and Australia.

The aim of the European Sero-Epidemiology Network is to establish comparability of the serological surveillance of vaccine-preventable diseases in Europe. The designated reference laboratory (RL) for measles, mumps, rubella (MMR) prepared and tested a panel of 151 sera by the reference enzyme immunoassay (rEIA). Laboratories in 21 countries tested the panel for antibodies against MMR using their usual assay (a total of 16 different EIAs) and the results were plotted against the reference results in order to obtain equations for the standardization of national serum surveys. The RL also tested the panel by the plaque neutralization test (PNT). Large differences in qualitative results were found compared to the RL. Well-fitting standardization equations with R2> or =0.8 were obtained for almost all laboratories through regression of the quantitative results against those of the RL. When compared to PNT, the rEIA had a sensitivity of 95.3%, 92.8% and 100% and a specificity of 100%, 87.1% and 92.8% for measles, mumps and rubella, respectively. The need for standardization was highlighted by substantial inter-country differences. Standardization was successful and the selected standardization equations allowed the conversion of local serological results into common units and enabled direct comparison of seroprevalence data of the participating countries.

Potential triggering infections of reactive arthritis.

OBJECTIVES: The aim of the study was to investigate possible triggering infections causing reactive arthritis (ReA) of urogenital origin. METHODS: One hundred and twenty ReA patients, 85 control group patients with other arthritides (61 with rheumatoid arthritis, 13 with osteoarthritis, and 11 with microcrystal arthritis), and 52 healthy persons were tested for urogenital tract inflammation and several infectious agents. Ligase chain reaction was used for detection of Chlamydia trachomatis (CT). Genital mycoplasmas Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) were tested using the Mycoplasma Duo Test (MDT). Only titres greater than 10(4) CCU/mL were accepted as pathogenecity threshold levels for Uu. RESULTS: Inflammation of the urogenital tract (most frequently urethritis in men and cervicitis in women) was found in 95% of patients with acute ReA. Possible causative pathogens were identified in 58% of ReA patients. CT was found in 29%, Uu in 21%, and Mh in 8% of patients with ReA. While CT and Uu were found more often in HLA-B27-positive than in HLA-B27-negative patients, this was statistically proved only for CT. In ReA males Uu was found four times more frequently than in men with other arthritides. CONCLUSIONS: In active ReA of urogenital origin, inflammation of the urogenital tract is found in the majority of patients. Although CT is the main microorganism associated with urethritis in men and cervicitis in women, mycoplasmas, especially Uu, may be possible aetiological factors for ReA.