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INTRODUÇÃO: O mecanismo de ação dos inibidores do co-transportador de sódio-glicose 2 (iSGLT2) consiste no aumento da glicosúria. Existe evidência da associação entre a sua toma e a ocorrência de infeções genitais. Porém, a associação com infeções do trato urinário (ITU) não está bem estabelecida. Pretende-se analisar a evidência atual sobre a associação entre iSGLT2 em doentes com diabetes mellitus tipo 2 e a ocorrência de ITU. MÉTODOS: Pesquisadas normas de orientação clínica, meta-análises (MA), revisões sistemáticas e ensaios clínicos controlados e aleatorizados (ECCA) entre outubro de 2011 e outubro de 2021 na The National Institute for Health and Care Excellence, The Cochrane Library e PubMed. Utilizados os termos MeSH “urinary tract infection”, “sodium-glucose transporter 2 inhibitors” e “diabetes mellitus, type 2”. Para atribuição dos níveis de evidência (NE) foi utilizada a escala Strength of Recommendation Taxonomy, da American Academy of Family Physicians. RESULTADOS: Dos 331 resultados identificados, 6 cumpriram os critérios de inclusão: 5 ECCA e 1 MA. Todos classificados com NE 2. A evidência da associação entre a toma de iSGLT2 e ITU foi apenas demonstrada, de forma estatisticamente significativa, na MA e relativamente à dapagliflozina na dosagem de 10 mg. CONCLUSÃO: Os estudos apresentam resultados heterogéneos, inconsistentes e de qualidade moderada. Os iSGLT2 têm afirmado o seu lugar no tratamento de múltiplas patologias pelo que impera a realização de estudos dirigidos à ocorrência de efeitos adversos como a frequência de ITU. Devem ainda compreender amostras de maior dimensão, diferentes moléculas e posologias, para a obtenção de evidência robusta.

Abstract Background In this study, the prevalence and persistence of anti-SARS-CoV-2 (severe acute respiratory syndrome-coronavirus) IgG was evaluated in volunteers 90 days after COVID-19 (coronavirus disease 2019) diagnosis by correlating response dynamics with clinical conditions, epidemiological characteristics, and disease severity. Methods The study recruited 200 volunteers aged 18 years or older of both sexes diagnosed with COVID-19. Of the 200 volunteers initially selected, the 135 individuals who underwent serological testing for anti-SARS-CoV-2 antibodies on the first visit to the laboratory, were invited to return, after 90 days, and provide a new blood sample for a second assessment of the presence of anti-SARS-CoV-2 IgG antibody. Disease severity and longevity of symptoms were evaluated for each individual and associated with the serological profile. Results Among the 135 individuals who underwent a previous serological test for anti-SARS-CoV-2 antibody, 125 showed reactivity to IgG (92.6%). Of the 125 individuals with detectable IgG in the first test, 87 (69.6%) showed persistence of this antibody after 90 days and 38 (30.4%) lost IgG reactivity in the second evaluation. The frequency of all reported symptoms was higher in individuals who maintained IgG persistence after 90 days of symptoms. Symptom manifestations lasted ≥21 days in the group with a persistent IgG response (39.6%) and ≤ 7 days in the group with a nonpersistent IgG response (50.0%). The length of hospital stay and supplemental oxygen use were higher in individuals with a persistent IgG response. Conclusions The results of the present study show a high frequency of loss of anti-SARS-CoV-2 IgG antibodies within 3 months after COVID-19 diagnosis in the Brazilian Amazon.

The present study evaluated the frequency of seropositivity for anti-SARS-CoV-2 (S1 and S2) total antibodies and anti-SARS-CoV-2 (receptor binding domain-RBD-S1) neutralizing antibodies in individuals vaccinated with the immunizing agent Coronavac. This was a cross-sectional study involving 358 individuals divided into two groups. Group 1 consisted of 205 volunteers who were tested for anti-SARS-CoV-2 total antibodies; group 2 consisted of 153 individuals tested for the presence of anti-SARS-CoV-2 neutralizing antibodies. Seropositivity was greater than 70% in both groups, although 17.6% and 20.9% of individuals showed no neutralizing or total antibody reactivity, respectively. The frequency of anti-SARS-CoV-2 total antibodies displayed a significantly different distribution between the sexes but not according to age. The frequency of anti-SARS-CoV-2 neutralizing antibodies was 93.3% (95% CI 68.1–99.8) in the age group from 21 to 40 years but significantly decreased with advancing age, and was 76.2% (95% CI 52.8–91.8) for 41 to 60 years, 72.5% (95% CI 62.8–80.9) for 61 to 80 years, and 46.7% (95% CI 21.3–73.4) for >80 years. Our results reveal a high prevalence of anti-SARS-CoV-2 total antibodies and anti-SARS-CoV-2 neutralizing antibodies in individuals who received both doses of the Coronavac vaccine, suggesting a lower effectiveness of the humoral immune response among those older than 60 years of age, which might be associated with senescence of the immune system.

BACKGROUND: Medication reconciliation is advocated to ensure the continuity, safety, and effective use of medicines across transitions of care. CASE REPORT: In this report, we describe the case of a 90-year-old female with previous diagnoses of atrial fibrillation and cutaneous metastatic breast cancer presenting with bilateral ulcerative lesions on the chest wall. The patient was diagnosed with Deep Vein Thrombosis at the Emergency Department and started on rivaroxaban, although the patient was already taking edoxaban. This therapeutic duplication was noticed only one week later, even though she was already experiencing significant bleeding managed through a prescribing cascade. Despite the technical error (action-based), it is possible to identify several weaknesses in the organisation's structure, which provided a trajectory of accident opportunity. CONCLUSION: Anticoagulants are ranked first for the highest priority to receive a medication reconciliation. To achieve an optimal level of medication reconciliation, we ought to recognise and correct latent failures. [ABSTRACT FROM AUTHOR]

ABSTRACT We assess the impact of climate change on the geographic distribution and productivity of Euterpe oleracea (Arecaceae), commonly called açaí. To construct the ecological niche model of E. oleracea, we used 95 points of occurrence, five bioclimatic variables in current and future climate scenarios and Maxent software. The Akaike Information Criteria (AIC) was used to rank the ability of the models (considering ecological, socioeconomic and spatial variables) to explain the variation in productivity of E. oleracea among 200 municipalities. The maps showed that regions with higher environmental suitability for E. oleracea were concentrated in northern and northeastern Brazil, which was similar to the spatial pattern of productivity data of E. oleracea. Future climate conditions tend to promote an increase in the geographical distribution of this species, even though the new regions are in the arch of Amazon deforestation. Only space and the environmental suitability (indicated by the ecological niche model) were important for explaining the productivity of E. oleracea. That is, municipalities that are more productive are located in more suitable environmental regions. Therefore, it is important to use niche models to explain demographic changes and to estimate species demographic attributes.

O mercado de derivativos tem crescido de forma impressionante nos últimos vinte anos, seja em termos de volume ou em termos de instrumentos financeiros disponíveis. Embora tenha havido perdas que ocorreram com empresas bastante conhecidas do público e aliada as inúmeras advertências dos meios de comunicação sobre os riscos inerentes a esses instrumentos, ainda assim, o mercado de derivativos tem sido usado por um grande número de empresas, já que esses instrumentos permitem transferir os riscos tanto de mercado como o de crédito para uma terceira parte. Entre as causas que originaram as perdas acima mencionadas figuram as devidas à relativa falta de conhecimento com que esses instrumentos têm sido utilizados. Além do mais, esses instrumentos sempre foram considerados complexos e um tanto sofisticados e num primeiro momento não foram contabilizados, sendo portanto considerados como itens fora do balanço, e dessa forma, muitas empresas usavam-nos para fugir das exigências das legislações, mantendo assim os riscos dos ativos no próprio balanço, quando deveriam justamente evitar esse tipo procedimento. Nesse artigo, nosso objetivo se concentrou nas definições do que vem a ser um instrumento derivativo, procurando mostrar a evolução na forma de contabilizá-los, finalizando com a abordagem realizada pelo SFAS 133 na forma de mensurar os derivativos, mostrando que a forma de contabilizá-los a valores justos ("fair value") é uma evolução quando se compara com o "velho" método do custo histórico.The derivatives market has been increasing at an impressive pace over the last twenty years, both in terms of traded volume and financial instruments available. Although losses occurred for companies whose names were familiar to the public in general, along with the innumerous warnings given by the media about the risks involved in this kind of instruments, derivatives have been used by a wide range of companies, since they allow for the transfer of either market or credit risk to third parties. The aforesaid losses were due to the relative lack of knowledge with which these instruments have been used. Moreover, these instruments were always considered complex and rather sophisticated and, in the first instance, they were not accounted for, i.e., they were considered offbalance sheet items and, consequently, many companies used them to escape from legal demands, thus maintaining the assets' risks in their balance sheets, when they should really avoid this kind of procedures. In this article, our objective was concentrated on the definitions of a derivative instrument, seeking to show the evolution in its accounting treatment. Finally, the approach of SFAS 133 is treated, which measures derivatives differently, demonstrating that their accounting treatment by means of fair value is an evolution in comparison with the "old" historical cost method.

Byline: T. W. O'Neill (1), W. Cockerill (1), C. Matthis (2), H. H. Raspe (2), M. Lunt (1), C. Cooper (3), D. Banzer (4), J. B. Cannata (5), M. Naves (5), B. Felsch (6), D. Felsenberg (7), J. Janott (8), O. Johnell (9), J. A. Kanis (10), G. Kragl (11), A. Lopes Vaz (12), G. Lyritis (13), P. Masaryk (14), G. Poor (15), D. M. Reid (16), W. Reisinger (17), C. Scheidt-Nave (18), J. J. Stepan (19), C. J. Todd (20), A. D. Woolf (21), J. Reeve (22), A. J. Silman (1) Keywords: Back pain; Disability; Prospective study; Vertebral fracture Abstract: Vertebral fractures are associated with back pain and disability. There are, however, few prospective data looking at back pain and disability following identification of radiographic vertebral fracture. The aim of this analysis was to determine the impact of radiographically identified vertebral fracture on the subsequent occurrence of back pain and disability. Women aged 50 years and over were recruited from population registers in 18 European centers for participation in the European Prospective Osteoporosis Study. Participants completed an interviewer-administered questionnaire which included questions about back pain in the past year and various activities of daily living, and they had lateral spine radiographs performed. Participants in these centers were followed prospectively and had repeat spine radiographs performed a mean of 3.7 years later. In addition they completed a questionnaire with the same baseline questions concerning back pain and activities of daily living. The presence of prevalent and incident vertebral fracture was defined using established morphometric criteria. The data were analyzed using logistic regression with back pain or disability (present or absent) at follow-up as the outcome variable with adjustment made for the baseline value of the variable. The study included 2,260 women, mean age 62.2 years. The mean time between baseline and follow-up survey was 5.0 years. Two hundred and forty participants had prevalent fractures at the baseline survey, and 85 developed incident fractures during follow-up. After adjustment for age, center, and the baseline level of disability, compared with those without baseline prevalent fracture, those with a prevalent fracture (odds ratio [OR]=1.4 95% confidence interval [CI] 1.0 to 2.0) or an incident fracture (OR=1.7 95% CI, 0.9 to 3.2) were more likely to report disability at follow-up, though the confidence intervals embraced unity. Those with both a prevalent and incident fracture, however, were significantly more likely to report disability at follow-up (OR=3.1 95% CI, 1.4 to 7.0). After adjustment for age, center, and frequency of back pain at baseline, compared with those without baseline vertebral fracture, those with a prevalent fracture were no more likely to report back pain at follow-up (OR=1.2 95%CI, 0.8 to 1.7). There was a small increased risk among those with a preexisting fracture who had sustained an incident fracture during follow-up (OR=1.6 95%CI, 0.6 to 4.1) though the confidence intervals embraced unity. In conclusion, although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture, women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living. Author Affiliation: (1) ARC Epidemiology Research Unit, University of Manchester, Manchester, M13 9PT, UK (2) Institute for Social Medicine, Medical University of Lubeck, Lubeck, Germany (3) MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton, UK (4) Department of Radiology, Behring Hospital, Berlin, Germany (5) Asturia General Hospital, Oviedo, Spain (6) Clinic for Internal Medicine, Jena, Germany (7) Department of Radiology and Nuclear Medicine, Free University, Berlin, Germany (8) Ruhr University, Bochum, Germany (9) Department of Orthopedics, Lund University, Malmo, Sweden (10) Centre for Metabolic Bone Disease, Sheffield, UK (11) Medical Academy, Erfurt, Germany (12) Hospital de San Joao, Oporto, Portugal (13) Laboratory for the Research of Musculoskeletal System, University of Athens, Athens, Greece (14) Institute of Rheumatic Diseases, Piestany, Slovakia (15) National Institute of Rheumatology and Physiotherapy, Budapest, Hungary (16) Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK (17) Institute for Diagnostic Radiology, Humboldt University, Berlin, Germany (18) Department of General Practice, University of Goettingen, Goettingen, Germany (19) Department of Medicine, Charles University, Prague, Czech Republic (20) School of Nursing, Midwifery and Health Visiting, University of Manchester, Manchester, UK (21) Department of Rheumatology, Royal Cornwall Hospital, Truro, UK (22) University Department of Medicine and Institute of Public Health, Cambridge, UK Article History: Registration Date: 12/02/2004 Received Date: 27/11/2003 Accepted Date: 11/02/2004 Online Date: 12/05/2004

Em 23 doentes psoriáticos, 9 dos quais sofriam de artrite, estudaram-se varios parametros hemostaticos e vasculares. Em comparação com um grupo normal verificou-se ligeiro acréscimo da actividade fibrinolítica basal, o qual se manteve apos oclusão venosa. A agregação plaquetária espontânea e a moderada tendência a hiperagregabilidade observada em alguns casos nao foram estatisticamente significativas. Os factores 1, II, V, VII + X, VIIIC, VIIIR:Ag, IX e os FDP apresentaram valores dentro dos limites normais, nomeadamente na resposta a oclusão venosa. As arteriopatias mostraram preferência pelo primeiro dedo das mãos e as provas funcionais sugerem preservação do tono vascular. Conclui-se pelo interesse em aprofundar alguns dos aspectos estudados.

OBJECTIVE: We recently showed, using a candidate gene approach in a case-control association study, that a 65-kb block encompassing tumor necrosis factor receptor-associated factor 1 (TRAF1) and C5 is strongly associated with rheumatoid arthritis (RA). Compared with case-control association studies, family-based studies have the added advantage of controlling potential differences in population structure and are not likely to be hampered by variation in population allele frequencies, as is seen for many genetic polymorphisms, including the TRAF1/C5 locus. The aim of this study was to confirm this association in populations of European origin by using a family-based approach. METHODS: A total of 1,356 western European white individuals from 452 'trio' families were genotyped for the rs10818488 polymorphism, using the TaqMan allelic discrimination assay. RESULTS: We observed evidence for association, demonstrating departure from Mendel's law, with an overtransmission of the rs10818488 A allele (A = 55%; P = 0.036). By taking into consideration parental phenotypes, we also observed an increased A allele frequency in affected versus unaffected parents (A = 64%; combined P = 0.015). Individuals carrying the A allele had a 1.2-fold increased risk of developing RA (allelic odds ratio 1.24, 95% confidence interval 1.04-1.50). CONCLUSION: Using a family-based study that is robust against population stratification, we provide evidence for the association of the TRAF1/C5 rs10818488 A allele and RA in populations of European descent, further substantiating our previous findings. Future functional studies should yield insight into the biologic relevance of this locus to the pathways involved in RA. [ABSTRACT FROM AUTHOR]

The integrin alpha(v)beta3, whose alpha(v) subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population. Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk.We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; P = 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; P = 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus 50% of transmission; P = 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; P = 0.002, odds ratio = 1.94, 95% confidence interval = 1.3-2.9). The rs3738919-C allele of the ITGAV gene is associated with RA in the European Caucasian population, suggesting ITGAV as a new minor RA susceptibility gene.

Unlabelled: More severe vertebral fractures have more personal impact. In the European Prospective Osteoporosis Study, more severe vertebral collapse was predictable from prior fracture characteristics. Subjects with bi-concave or crush fractures at baseline had a 2-fold increase in incident fracture size and thus increased risk of a disabling future fracture., Introduction: According to Euler's buckling theory, loss of horizontal trabeculae in vertebrae increases the risk of fracture and suggests that the extent of vertebral collapse will be increased in proportion. We tested the hypothesis that the characteristics of a baseline deformity would influence the size of a subsequent deformity., Methods: In 207 subjects participating in the European Prospective Osteoporosis Study who suffered an incident spine fracture in a previously normal vertebra, we estimated loss of volume (fracture size) from plane film images of all vertebral bodies that were classified as having a new fracture. The sum of the three vertebral heights (anterior, mid-body, and posterior) obtained at follow-up was subtracted from the sum of the same measures at baseline. Each of the summed height loss for vertebrae with a McCloskey-Kanis deformity on the second film was expressed as a percentage., Results and Conclusions: In univariate models, the numbers of baseline deformities and the clinical category of the most severe baseline deformity were each significantly associated with the size of the most severe incident fracture and with the cumulated sum of all vertebral height losses. In multivariate modeling, age and the clinical category of the baseline deformity (crush > bi-concave > uni-concave > wedge) were the strongest determinants of both more severe and cumulative height loss. Baseline biconcave and crush fractures were associated at follow-up with new fractures that were approximately twice as large as those seen with other types of deformity or who previously had undeformed spines. In conclusion, the characteristics of a baseline vertebral deformity determines statistically the magnitude of vertebral body volume lost when a subsequent fracture occurs. Because severity of fracture and number of fractures are determinants of impact, the results should improve prediction of the future personal impact of osteoporosis once a baseline prevalent deformity has been identified.

There is important geographic variation in the occurrence of the major osteoporotic fractures across Europe. The aim of this study was to determine whether between-center variation in limb fracture rates across Europe could be explained by variation in the incidence of falls. Men and women, aged 50-79 years, were recruited from population-based registers in 30 European centers. Subjects were followed by postal questionnaire to ascertain the occurrence of incident fractures, and were also asked about the occurrence and number of recent falls. Self-reported fractures were confirmed, where possible, by review of the radiographs, medical record, or subject interview. The age- and gender-adjusted incidence of falls was calculated by center using Poisson regression. Poisson regression was also used to assess the extent to which between-center differences in the incidence of limb fractures could be explained by differences in the age- and gender-adjusted incidence of falls at those centers. In all, 6302 men (mean age 63.9 years) and 6761 women (mean age 63.1 years) completed at least one questionnaire concerning fractures and falls. During a median follow-up time of 3 years, 3647 falls were reported by men and 4783 by women. After adjusting for age and gender, there was evidence of significant between-center differences in the occurrence of falls. There was also between-center variation in the occurrence of upper limb, lower limb, and distal forearm fractures. Variation in the age- and gender-adjusted center-specific fall rates explained 24%, 14%, and 6% of the between-center variation in incidence of distal forearm and upper and lower limb fractures, respectively. Given the constraints inherent in such an analysis, in men and women aged 50-79 years, variation in fall rates could explain a significant proportion of the between-center variation in the incidence of limb fracture across Europe., (Copyright 2002 by Elsevier Science Inc.)

Vertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14,011 men and women aged 50 years and over were recruited from population-based registers in 29 European centers and had an interviewer-administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films--plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey-Kanis method) in the follow-up film. There were 3174 men, mean age 63.1 years, and 3,614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1,000 person years (pyr) in women and 5.7/1,000 pyr in men. The age-standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar-12.1/1,000 pyr and 6.8/1,000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population-based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.

Unlabelled: The genetic predisposition for rheumatoid arthritis (RA) is only partly explained by the HLA locus and most genetic factors involved in the susceptibility (and/or severity) of the disease await further identification. The first European genome scan in RA families provided suggestive evidence for linkage with a region (3.1/3q13) on chromosome 3, but many other potential RA susceptibility genes have yet to be analysed., Aims: To perform a linkage analysis with microsatellite markers located in the vicinity of the interleukin-1 (IL-1) gene superfamily, the IL-10 gene and the IL-4 gene cluster which might be considered putative candidate loci for RA., Methods: 107 Caucasoid European RA sibpairs from 90 nuclear families were genotyped for markers flanking the genes for the IL-1 superfamily, IL-10 and the IL-4 gene cluster. Linkage analysis based on the identity by descent (IBD) in affected siblings was analysed with the program SIBPALNA. Affected sibpairs were stratified according to the identity by state (IBS) for three markers in the HLA region (DRB1 oligotyping, D6S276 and TNFa microsatellites) and to the presence/absence of erosive disease on X-ray examination., Results: Analysis of the whole family set showed an excess of allele sharing for markers of the IL-1 gene cluster (IBD 60%; P = 0.012) but not for IL-10 or IL-4. After stratification, the evidence of linkage to IL-1 was restricted to HLA concordant sibpairs (n = 32; IBD 70%; P = 0.006). Some evidence of linkage to IL-10 was also observed in HLA concordant sibpairs (IBD 66%; P = 0.03) and in sibpairs with erosive disease (n = 61; IBD 62%; P = 0.02)., Conclusions: We found suggestive evidence of linkage of RA to the IL-1 locus. The increased linkage to IL-1 and IL-10 in HLA-identical sibs suggests a possible interaction between these cytokines and the HLA loci. Moreover IL-10 could interact with HLA factors in predisposing to erosive disease. These results need to be tested in additional families for consistency and replication.

Objective: It has been proposed that noninherited maternal HLA-DR antigens (NIMA) might play a role in the susceptibility for rheumatoid arthritis (RA). This hypothesis has not been thoroughly tested in patients with familial RA, in whom genetic factors, either inherited or not, might have stronger influence than in patients with sporadic RA. We investigated the NIMA hypothesis in a large cohort of European patients with familial RA., Methods: The distribution of NIMA, noninherited paternal antigens (NIPA), and inherited HLA-DR antigens was assessed in patients with familial RA from all family sets collected from 1996 onwards by the ECRAF. HLA-DRB1 oligotyping from patients and all available nonaffected siblings and parents was carried out. Familial RA was defined by the presence of at least 2 affected first-degree relatives in the same family. The frequencies of HLA-DR NIMA and NIPA were compared using odds ratios after stratification for HLA-DR*04, *0401, and/or *0404 and shared epitope (SE) status. NIMA/NIPA that coincided with inherited parental HLA-DR antigens were considered redundant and were excluded from analysis., Results: NIMA and NIPA could be analyzed in 165 RA patients with familial RA and 84 nonaffected siblings. Patients were predominantly female, rheumatoid factor positive, and had erosive disease (81, 75, and 84%, respectively). Possession of HLA-DR*04 and *0401/*0404 alleles tended be more frequent in patients than in nonaffected siblings but this did not reach statistical significance. SE possession was similar in patients and healthy siblings, although the former had a double dose SE more often (37.6 vs 17.8%; p = 0.002). Transmission of SE encoding alleles from parents to offspring was skewed only in patients [OR (95% CI) 3.56 (2.55-4.95) vs 1.16 (0.75-1.79) in nonaffected siblings]. Using the NIPA as control, the frequencies of HLA-DRB1*04, *0401/*0404, and SE positive NIMA were not increased in patients lacking these susceptibility alleles. The frequencies of NIMA encoding susceptibility alleles in DR*04 and *0401/*0404 negative patients were lower than in nonaffected siblings., Conclusion: Our results corroborate the association between RA and inherited SE alleles and do not support a role for noninherited HLA-DR maternal antigens in the susceptibility for familial RA.

Objective: To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral) and the original CyA formulation (Sandimmun), in patients with severe active rheumatoid arthritis (RA), over a 12-month period., Methods: In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients' assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals., Results: Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients' assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups., Conclusion: These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.

The aims of this study were to determine common international risk factors for hip fracture in women aged 50 years or more. We studied women aged 50 years or more who sustained a hip fracture in 14 centers from Portugal, Spain, France, Italy, Greece, and Turkey over a 1-year period. Women aged 50 years or more selected from the neighborhood or population registers served as controls. Cases and controls were interviewed using a structured questionnaire on work, physical activity, exposure to sunlight, reproductive, history and gynecologic status, height, weight, mental score, and consumption of tobacco, alcohol, calcium, coffee, and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), short fertile period, low physical activity. lack of sunlight exposure, low milk consumption, no consumption of tea, and a poor mental score. No significant adverse effects of coffee or smoking were observed. Moderate intake of spirits was a protective factor in young adulthood, but otherwise no significant effect of alcohol intake was observed. For some risks, a threshold effect was observed. A low BMI and milk consumption were significant risks only in the lowest 50% and 10% of the population, respectively. A late menarche, poor mental score, low BMI and physical activity, low exposure to sunlight, and a low consumption of calcium and tea remained independent risk factors after multivariate analysis, accounting for 70% of hip fractures. Excluding mental score and age at menarche (not potentially reversible), the attributable risk was 56%. Thus, about half of the hip fractures could be explained on the basis of the potentially reversible risk factors sought. In contrast, the use of risk factors to "predict" hip fractures had moderate sensitivity and specificity. We conclude that variations in lifestyle factors are associated with significant differences in the risk of hip fracture, account for a large component of the total risk, and may be of some value in selecting individuals at high risk.

A double-blind trial was carried out in 40 out-patients with unilateral osteoarthrosis of the knee to compare the efficacy and tolerance of oral treatment with 1.5 g glucosamine sulphate or 1.2 g ibuprofen daily over a period of 8 weeks. Pain scores decreased faster during the first 2 weeks in the ibuprofen than in the glucosamine treatment group. Although the rate of decrease was slower, the reduction in pain scores was continued throughout the trial period in patients an glucosamine and the difference between the two groups turned significantly in favour of glucosamine at Week 8. No significant differences were observed in swelling or any of the other parameters monitored. Tolerance was satisfactory with both treatments, with only minor complaints being reported by 2 patients on glucosamine compared with 5 patients on ibuprofen.