Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis

Introduction: Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA. Methods: Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value. Results: With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity. Conclusions: CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.

Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia (Spain).

OBJECTIVES: Polypharmacy is one of the main management issues in public health policies because of its financial impact and the increasing number of people involved. The polymedicated population according to their demographic and therapeutic profile and the cost for the public healthcare system were characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered). PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were those with a consumption of ≥16 drugs/month. MAIN OUTCOMES MEASURES: The study variables were related to age, gender and medication intake obtained from the 2008 census and records of prescriptions dispensed in pharmacies and charged to the public health system. RESULTS: There were 36 880 polymedicated patients (women: 64.2%; average age: 74.5±10.9 years). The total number of prescriptions billed in 2008 was 2 266 830 (2 272 920 total package units). The most polymedicated group (up to 40% of the total prescriptions) was patients between 75 and 84 years old. The average number of prescriptions billed monthly per patient was 32±2, with an average cost of 452.7±27.5. The total cost of those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The groups N, C, A, R and M represented 71.4% of the total number of drug package units dispensed to polymedicated patients. Great variability was found between the medication profiles of men and women, and between age groups; greater discrepancies were found in paediatric patients (5-14 years) and the elderly (≥65 years). CONCLUSIONS: This study provides essential information to take steps towards rational drug use and a structured approach in the polymedicated population in primary healthcare.

Menschliche Bedürfnisse und Parteipolitik

Im Jahre 1978 lag die Selbstmordrate in der Bundesrepublik Deutschland einschließlich Berlin-West mit 22,2 auf 100000 Einwohner um 1,7 höher als zehn Jahre zuvor. Im gleichen Zeitraum etwa (1970-1979) stieg die jährliche Anzahl der Drogentoten von knapp 30 auf über 600. Eigentumsdelikte (Diebstahl, Betrug, Unterschlagung) und schwere Körperverletzungen nahmen von 1969 bis 1979 jeweils um mehr als 60 Prozent zu. Der Zigarettenkonsum erhöhte sich zwischen 1965 und 1979 um mehr als ein Viertel, die Zahl der behandlungsbe-dürftigen Alkoholkranken (ab 1968) um 450 Prozent. Der Verbrauch von Psychopharmaka hat sich währenddessen ungefähr verdoppelt.

La grande Saulière ; Ma tante Hermine / par Th. Bentzon

Collection : Bibliothèque contemporaine

Commentary : beyond vague causal effect estimation of obesity on health outcomes

In the current issue of epidemiology, Danaei and colleagues elegantly estimated both the direct effect and the indirect effect-that is, the effect mediated by blood pressure, cholesterol, glucose, fibrinogen, and high-sensitivity C-reactive protein-of body mass index (BMI) on the risk of coronary heart disease (CHD). they analyzed data from 9 cohort studies including 58,322 patients and 9459 CHD events, with baseline measurements between 1954 and 2001. Using sophisticated and cutting-edge methods for direct and indirect effect estimations, the authors estimated that half of the risk of overweight and obesity would be mediated by blood pressure, cholesterol, and glucose. Few additional percentage points of the risk would be mediated by fibrinogen and hs-CRP. How should we understand these estimates? Can we say that if obese persons reduce their body weight and reach a normal body weight, their excess risk of CHD would be reduced by half through an improvement in these mediators and by half through the reduction in BmI itself? Is that also true if these individuals are prevented from becoming obese in the first place? Can we also conclude that if these mediators are well controlled in obese individuals through other means than a body weight reduction, their excess risk of CHD would be reduced by half? Let us confront these estimates with observations from studies evaluating 2 interventions to reduce body weight, that is, bariatric surgery in patients with severe obesity and intensive lifestyle intervention in overweight patients with diabetes

Necessidades hídricas de bananeira tipo Terra em condições de tabuleiros costeiros

O objetivo deste trabalho foi avaliar os efeitos de diferentes lâminas de água nas variáveis morfofisiológicas e de produção de três cultivares de bananeira do tipo Terra. Utilizou-se o delineamento experimental de blocos ao acaso, em arranjo fatorial com 12 tratamentos e três repetições. Os tratamentos consistiram de lâminas de água correspondentes a 33, 66, 99 e 120% da evapotranspiração da cultura (ETc), além do controle sem irrigação, e das cultivares Terra Maranhão, Terrinha e D'Angola. Avaliaram-se as variáveis morfofisiológicas: altura de planta, diâmetro do pseudocaule, área foliar, condutância estomática e, na colheita, número de dedos e de pencas, e peso de pencas por cacho. Os coeficientes de cultura das cultivares de bananeira tipo Terra foram obtidos a partir da melhor combinação de produtividade e eficiência de uso de água. As lâminas de água de uso consuntivo de 1.599 mm (1,20 da ETc), 922 mm (0,84 da ETc) e 940 mm (1,06 da ETc) correspondem às máximas produtividades e eficiências de uso de água das cultivares Terra Maranhão, Terrinha e D'Angola, respectivamente.

Zyoptix-LASIK : sarveiskalvon taittovirhekirurgian aiheuttamat komplikaatiot myopian korjaamisessa

Opinnäytetyön tarkoituksena oli tutkia sarveiskalvon taittovirhekirurgian aiheuttamia komplikaatioita ja niiden ilmenemiseen vaikuttavia tekijöitä myopian korjaamisessa. Tarkastelun kohteena olivat myös leikkaustuloksen pysyvyys, regressio ja ylikorjaukset kuukauden, kuuden kuukauden ja vuoden kuluttua Zyoptix®LASIK-leikkauksesta. Tutkimus oli laadultaan kvantitatiivinen ja se toteutettiin yhteistyössä Eiran sairaalan kanssa. Sain käyttööni Eiran sairaalan potilaskortiston, josta siirsin tarvittavat tiedot Datagraph-ohjelmaan. Tutkimusjoukko muodostui 322 myooppisesta silmästä, jotka silmäkirurgi Harri Koskela leikkasi Eiran sairaalassa tammi-kesäkuussa vuonna 2005 Zyoptix®LASIK-leikkausmenetelmällä. Tutkimustulosten mukaan komplikaatioita esiintyi vain 1,2 %:lla koko tutkimusjoukosta. Myopian määrällä ei tutkimuksen mukaan ollut tilastollisesti merkitsevää vaikutusta komplikaatioiden ilmenemiseen eikä leikkaustuloksen pysyvyyteen. Esiintyneitä komplikaatioita olivat debris, läpän dislokaatio, haze ja epiteelin kasvu. Eniten komplikaatioita esiintyi erittäin suuriasteisessa myopiassa, jolloin myös sarveiskalvon paksuus ja sarveiskalvolle tehtävän läpän paksuus olivat pienempiä verrattuna vähäisempään myopian määrään. Ablaatiosyvyys korreloi negatiivisesti taittovirheen määrän kanssa, jolloin myopian määrän kasvaessa ablaatiosyvyys kasvoi tilastollisesti erittäin merkitsevästi. Leikkaustulos oli pysyvä kuukauden ja kuuden kuukauden kuluttua Zyoptix®LASIK-leikkauksesta riippumatta myopian määrästä. Vuoden kuluttua leikkauksesta suurilla myoopeilla tapahtui lievää regressiota. Tulevaisuudessa taittovirhekirurgia on tärkeä taittovirheen korjausmuoto silmälasien ja piilolinssien ohella. Opinnäytetyö tukee ammattiosaamistani toimiessani näönhuollon asiantuntijana. Tutkimuksen suuren otoskoon vuoksi opinnäytetyön tulosta voi pitää luotettavana.

Results of An International Study of Quantitative BCR/ABL Assays Using Defined RNA Samples

Molecular monitoring of BCR/ABL transcripts by real time quantitative reverse transcription PCR (qRT-PCR) is an essential technique for clinical management of patients with BCR/ABL-positive CML and ALL. Though quantitative BCR/ABL assays are performed in hundreds of laboratories worldwide, results among these laboratories cannot be reliably compared due to heterogeneity in test methods, data analysis, reporting, and lack of quantitative standards. Recent efforts towards standardization have been limited in scope. Aliquots of RNA were sent to clinical test centers worldwide in order to evaluate methods and reporting for e1a2, b2a2, and b3a2 transcript levels using their own qRT-PCR assays. Total RNA was isolated from tissue culture cells that expressed each of the different BCR/ABL transcripts. Serial log dilutions were prepared, ranging from 100 to 10-5, in RNA isolated from HL60 cells. Laboratories performed 5 independent qRT-PCR reactions for each sample type at each dilution. In addition, 15 qRT-PCR reactions of the 10-3 b3a2 RNA dilution were run to assess reproducibility within and between laboratories. Participants were asked to run the samples following their standard protocols and to report cycle threshold (Ct), quantitative values for BCR/ABL and housekeeping genes, and ratios of BCR/ABL to housekeeping genes for each sample RNA. Thirty-seven (n=37) participants have submitted qRT-PCR results for analysis (36, 37, and 34 labs generated data for b2a2, b3a2, and e1a2, respectively). The limit of detection for this study was defined as the lowest dilution that a Ct value could be detected for all 5 replicates. For b2a2, 15, 16, 4, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. For b3a2, 20, 13, and 4 labs showed a limit of detection at the 10-5, 10-4, and 10-3 dilutions, respectively. For e1a2, 10, 21, 2, and 1 lab(s) showed a limit of detection at the 10-5, 10-4, 10-3, and 10-2 dilutions, respectively. Log %BCR/ABL ratio values provided a method for comparing results between the different laboratories for each BCR/ABL dilution series. Linear regression analysis revealed concordance among the majority of participant data over the 10-1 to 10-4 dilutions. The overall slope values showed comparable results among the majority of b2a2 (mean=0.939; median=0.9627; range (0.399 - 1.1872)), b3a2 (mean=0.925; median=0.922; range (0.625 - 1.140)), and e1a2 (mean=0.897; median=0.909; range (0.5174 - 1.138)) laboratory results (Fig. 1-3)). Thirty-four (n=34) out of the 37 laboratories reported Ct values for all 15 replicates and only those with a complete data set were included in the inter-lab calculations. Eleven laboratories either did not report their copy number data or used other reporting units such as nanograms or cell numbers; therefore, only 26 laboratories were included in the overall analysis of copy numbers. The median copy number was 348.4, with a range from 15.6 to 547,000 copies (approximately a 4.5 log difference); the median intra-lab %CV was 19.2% with a range from 4.2% to 82.6%. While our international performance evaluation using serially diluted RNA samples has reinforced the fact that heterogeneity exists among clinical laboratories, it has also demonstrated that performance within a laboratory is overall very consistent. Accordingly, the availability of defined BCR/ABL RNAs may facilitate the validation of all phases of quantitative BCR/ABL analysis and may be extremely useful as a tool for monitoring assay performance. Ongoing analyses of these materials, along with the development of additional control materials, may solidify consensus around their application in routine laboratory testing and possible integration in worldwide efforts to standardize quantitative BCR/ABL testing.

Medication exposure during pregnancy: a pilot pharmacovigilance system using health and demographic surveillance platform.

BACKGROUND: There is limited safety information on most drugs used during pregnancy. This is especially true for medication against tropical diseases because pharmacovigilance systems are not much developed in these settings. The aim of the present study was to demonstrate feasibility of using Health and Demographic Surveillance System (HDSS) as a platform to monitor drug safety in pregnancy. METHODS: Pregnant women with gestational age below 20 weeks were recruited from Reproductive and Child Health (RCH) clinics or from monthly house visits carried out for the HDSS. A structured questionnaire was used to interview pregnant women. Participants were followed on monthly basis to record any new drug used as well as pregnancy outcome. RESULTS: 1089 pregnant women were recruited; 994 (91.3%) completed the follow-up until delivery. 98% women reported to have taken at least one medication during pregnancy, mainly those used in antenatal programmes. Other most reported drugs were analgesics (24%), antibiotics (17%), and antimalarial (15%), excluding IPTp. Artemether-lumefantrine (AL) was the most used antimalarial for treating illness by nearly 3/4 compared to other groups of malaria drugs. Overall, antimalarial and antibiotic exposures in pregnancy were not significantly associated with adverse pregnancy outcome. Iron and folic acid supplementation were associated with decreased risk of miscarriage/stillbirth (OR 0.1; 0.08 - 0.3). CONCLUSION: Almost all women were exposed to medication during pregnancy. Exposure to iron and folic acid had a beneficial effect on pregnancy outcome. HDSS proved to be a useful platform to establish a reliable pharmacovigilance system in resource-limited countries. Widening drug safety information is essential to facilitate evidence based risk-benefit decision for treatment during pregnancy, a major challenge with newly marketed medicines.