Browsing by Subject "AMERICAN-COLLEGE"

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  • NORD STAR Study Grp; Hetland, Merete Lund; Haavardsholm, Espen A.; Rudin, Anna; Nordström, Dan; van Vollenhoven, Ronald (2020)
    OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
  • Kuuliala, Krista; Kuuliala, Antti; Koivuniemi, Riitta; Kautiainen, Hannu; Repo, Heikki; Leirisalo-Repo, Marjatta (2017)
    Background: We found recently that baseline signal transducer and activator of transcription 3 phosphorylation in peripheral blood CD4(+) T cells of patients with early rheumatoid arthritis (RA) is associated with treatment response to synthetic disease-modifying antirheumatic drugs (DMARDs). This prompted us to study the baseline phosphorylation profiles of Janus kinases (JAKs) in blood leukocytes with respect to treatment response in early RA. Methods: Thirty-five DMARD-naive patients with early RA provided blood samples for whole blood flow cytometric determination of phosphorylation of JAKs in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes. Treatment response was determined after 1 year of treatment with synthetic DMARDs, with remission defined as absence of tender and swollen joints and normal erythrocyte sedimentation rate. Exact logistic regression was used to investigate the association of baseline variables with treatment response. Ninety-five percent CIs of means were estimated by bias-corrected bootstrapping. Results: High JAK3 phosphorylation in CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes and low JAK2 phosphorylation in CD14(+) monocytes were significantly associated with remission following treatment with synthetic DMARDs. Conclusions: Baseline JAK phosphorylation profile in peripheral blood leukocytes may provide a means to predict treatment response achieved by synthetic DMARDs among patients with early RA.
  • Taskinen, Marja-Riitta; Del Prato, Stefano; Bujas-Bobanovic, Maja; Louie, Michael J.; Letierce, Alexia; Thompson, Desmond; Colhoun, Helen M. (2018)
    Background and aims: Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, significantly reduces low-density lipoprotein cholesterol (LDL-C). We evaluated the efficacy and safety of alirocumab in individuals with type 2 diabetes mellitus (T2DM) with versus without mixed dyslipidaemia (MDL, defined as baseline LDL-C >= 70 mg/dL [1.8 mmol/L] and triglycerides >= 150mg/dL [1.7 mmol/L]). Methods: Data from 812 individuals with T2DM, from the placebo-controlled, 78-week, Phase 3 ODYSSEY LONG TERM trial of alirocumab 150mg every 2 weeks (Q2W), on a background of maximally tolerated statins +/- other lipid-lowering therapies, were pooled according to MDL status. Efficacy endpoints included percentage change from baseline to Week 24 in calculated LDL-C and other lipids/lipoproteins. Results: In individuals with T2DM who received alirocumab 150mg Q2W, mean LDL-C changes from baseline to Week 24 were -62.6% (vs. -6.0% with placebo) in those with MDL and -56.1% (vs. 5.6%) in those without MDL, with no significant between-group difference (p-interaction = 0.0842). Risk-based LDL-C goals ( Conclusions: Reductions in LDL-C and other lipids with alirocumab, as well as safety and tolerability, were comparable between individuals with T2DM and with versus without MDL. (c) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
  • Clarke, Angus J.; Wallgren-Pettersson, Carina (2019)
    Difficult ethical issues arise for patients and professionals in medical genetics, and often relate to the patient’s family or their social context. Tackling these issues requires sensitivity to nuances of communication and a commitment to clarity and consistency. It also benefits from an awareness of different approaches to ethical theory. Many of the ethical problems encountered in genetics relate to tensions between the wishes or interests of different people, sometimes even people who do not (yet) exist or exist as embryos, either in an established pregnancy or in vitro. Concern for the long-term welfare of a child or young person, or possible future children, or for other members of the family, may lead to tensions felt by the patient (client) in genetic counselling. Differences in perspective may also arise between the patient and professional when the latter recommends disclosure of information to relatives and the patient finds that too difficult, or when the professional considers the genetic testing of a child, sought by parents, to be inappropriate. The expectations of a patient’s community may also lead to the differences in perspective between patient and counsellor. Recent developments of genetic technology permit genome-wide investigations. These have generated additional and more complex data that amplify and exacerbate some pre-existing ethical problems, including those presented by incidental (additional sought and secondary) findings and the recognition of variants currently of uncertain significance, so that reports of genomic investigations may often be provisional rather than definitive. Experience is being gained with these problems but substantial challenges are likely to persist in the long term.
  • Sartelli, Massimo; Kluger, Yoram; Ansaloni, Luca; Coccolini, Federico; Baiocchi, Gian Luca; Hardcastle, Timothy C.; Moore, Ernest E.; May, Addison K.; Itani, Kamal M. F.; Fry, Donald E.; Boermeester, Marja A.; Guirao, Xavier; Napolitano, Lena; Sawyer, Robert G.; Rasa, Kemal; Abu-Zidan, Fikri M.; Adesunkanmi, Abdulrashid K.; Atanasov, Boyko; Augustin, Goran; Bala, Miklosh; Cainzos, Miguel A.; Chichom-Mefire, Alain; Cortese, Francesco; Damaskos, Dimitris; Delibegovic, Samir; Demetrashvili, Zaza; De Simone, Belinda; Duane, Therese M.; Ghnnam, Wagih; Gkiokas, George; Gomes, Carlos A.; Hecker, Andreas; Karamarkovic, Aleksandar; Kenig, Jakub; Khokha, Vladimir; Kong, Victor; Isik, Arda; Leppäniemi, Ari; Litvin, Andrey; Lostoridis, Eftychios; Machain, Gustavo M.; Marwah, Sanjay; McFarlane, Michael; Mesina, Cristian; Negoi, Ionut; Olaoye, Iyiade; Pintar, Tadeja; Pupelis, Guntars; Rems, Miran; Rubio-Perez, Ines; Sakakushev, Boris; Segovia-Lohse, Helmut; Siribumrungwong, Boonying; Talving, Peep; Ulrych, Jan; Vereczkei, Andras G.; Labricciosa, Francesco M.; Catena, Fausto (2018)
    Despite evidence supporting the effectiveness of best practices of infection prevention and management, many surgeons worldwide fail to implement them. Evidence-based practices tend to be underused in routine practice. Surgeons with knowledge in surgical infections should provide feedback to prescribers and integrate best practices among surgeons and implement changes within their team. Identifying a local opinion leader to serve as a champion within the surgical department may be important. The "surgeon champion" can integrate best clinical practices of infection prevention and management, drive behavior change in their colleagues, and interact with both infection control teams in promoting antimicrobial stewardship.
  • Perpetuo, Ines Pedro; Caetano-Lopes, Joana; Rodrigues, Ana Maria; Campanilho-Marques, Raquel; Ponte, Cristina; Canhao, Helena; Ainola, Mari; Fonseca, Joao Eurico (2017)
    Objective Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that ultimately leads to bone erosions and joint destruction. Methotrexate (MTX) slows bone damage but the mechanism by which it acts is still unknown. In this study, we aimed to assess the effect of MTX and low-dose prednisolone (PDN) on circulating osteoclast (OC) precursors and OC differentiation in patients with RA. Methods Patients with RA before and at least 6 months after MTX therapy were analysed and compared with healthy donors. A blood sample was collected in order to assess receptor activator of NF-kappa beta (RANK) ligand surface expression on circulating leucocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines and OC differentiation assays were performed. Results Classical activation markers of monocytes and RANK increased in patients with RA at baseline, compared with control healthy donors, and after MTX and low-dose PDN (MTX+PDN) exposure they decreased to control levels. Although the number of OC was not different between groups, the percentage of resorbed area and the resorbed area per pit reduced after treatment. Serum soluble receptor activator of nuclear factor-kappa (RANKL) levels increased at baseline compared with healthy donors and normalised after therapy. Conclusion Our results suggest that MTX+PDN play an important role in downregulating OC function, which we believe occurs through the decrease in RANK surface expression in monocytes.
  • Costantini, Alice; Skarp, Sini; Kampe, Anders; Mäkitie, Riikka E.; Pettersson, Maria; Männikkö, Minna; Jiao, Hong; Taylan, Fulya; Lindstrand, Anna; Mäkitie, Outi (2018)
    Early-onset osteoporosis is characterized by low bone mineral density (BMD) and fractures since childhood or young adulthood. Several monogenic forms have been identified but the contributing genes remain inadequately characterized. In search for novel variants and novel candidate loci, we screened a cohort of 70 young subjects with mild to severe skeletal fragility for rare copy-number variants (CNVs). Our study cohort included 15 subjects with primary osteoporosis before age 30 years and 55 subjects with a pathological fracture history and low or normal BMD before age 16 years. A custom-made high-resolution comparative genomic hybridization array with enriched probe density in >1,150 genes important for bone metabolism and ciliary function was used to search for CNVs. We identified altogether 14 rare CNVs. Seven intronic aberrations were classified as likely benign. Five CNVs of unknown clinical significance affected coding regions of genes not previously associated with skeletal fragility (ETV1-DGKB, AGBL2, ATM, RPS6KL1-PGF, and SCN4A). Finally, two CNVs were pathogenic and likely pathogenic, respectively: a 4 kb deletion involving exons 1-4 of COL1A2 (NM_000089.3) and a 12.5 kb duplication of exon 3 in PLS3 (NM_005032.6). Although both genes have been linked to monogenic forms of osteoporosis, COL1A2 deletions are rare and PLS3 duplications have not been described previously. Both CNVs were identified in subjects with significant osteoporosis and segregated with osteoporosis within the families. Our study expands the number of pathogenic CNVs in monogenic skeletal fragility and shows the validity of targeted CNV screening to potentially pinpoint novel candidate loci in early-onset osteoporosis.
  • Hammer, Hilde Berner; Hansen, Inger Marie Jensen; Järvinen, Pentti; Leirisalo-Repo, Marjatta; Ziegelasch, Michael; Agular, Birte; Terslev, Lene (2021)
    Objectives. Given that subjective variables might reduce remission by composite DAS (CDAS), the main objectives were to explore whether RA patients with mainly tender vs mainly swollen joints had differences in patient-reported outcome measures (PROMs), clinical or US assessments or in achieving remission defined by CDAS or US. Methods. In a Nordic multicentre study, RA patients initiating tocilizumab were assessed by PROMs, clinical, laboratory and US assessments (36 joints and 4 tendons) at baseline, 4, 12 and 24 weeks. Remission was defined according to clinical disease activity index (CDAI)/Boolean or no Doppler activity present. Tender-swollen joint differences (TSJDs) were calculated. Statistics exploring changes over time/differences between groups included Wilcoxon, Mann-Whitney, Kruskal-Wallis and Spearman tests. Results. One hundred and ten patients were included [mean (S.D.) age 55.6 (12.1) years, RA duration 8.7 (9.5) years]. All PROMs, clinical, laboratory and US scores decreased during follow-up (P < 0.001). During follow-up, tender joint counts were correlated primarily with PROMs [r = 0.24-0.56 (P < 0.05-0.001)] and swollen joint counts with US synovitis scores [r = 0.33-0.72 (P < 0.05-0.001)]. At 24 weeks, patients with TSJD > 0 had higher PROMs and CDAI (P < 0.05-0.001) but lower US synovitis scores (P < 0.05). Remission by CDAI/Boolean was seen in 26-34% and by Doppler 53%, but only 2-3% of patients with TSJD > 0 achieved CDAI/Boolean remission. Conclusion. Patients with more tender than swollen joints scored higher on subjective assessments but had less US synovitis. They seldom achieved CDAS remission despite many being in Doppler remission. If patients with predominantly tender joints do not reach CDAS remission, objective assessments of inflammation should be performed.
  • Kerola, Tuomas; Eranti, Antti; Aro, Aapo L.; Haukilahti, M. Anette; Holkeri, Arttu; Junttila, M. Juhani; Kenttä, Tuomas V.; Rissanen, Harri; Vittinghoff, Eric; Knekt, Paul; Heliövaara, Markku; Huikuri, Heikki V.; Marcus, Gregory M. (2019)
    IMPORTANCE Pacemaker implantations as a treatment for atrioventricular (AV) block are increasing worldwide. Prevention strategies for AV block are lacking because modifiable risk factors have not yet been identified. OBJECTIVE To identify risk factors for AV block in community-dwelling individuals. DESIGN, SETTING, AND PARTICIPANTS In this population-based cohort study, data from the Mini-Finland Health Survey, conducted from January 1, 1978, to December 31, 1980, were used to examine demographics, comorbidities, habits, and laboratory and electrocardiographic (ECG) measurements as potential risk factors for incident AV block. Data were ascertained during follow-up from January 1, 1987, through December 31, 2011, using a nationwide registry. A total of 6146 community-dwelling individuals were included in the analysis performed from January 15 through April 3, 2018. MAIN OUTCOMES AND MEASURES Incidence of AV block (hospitalization for second-or third-degree AV block). RESULTS Among the 6146 participants (3449 [56.1%] women; mean [SD] age, 49.2 [12.9] years), 529 (8.6%) had ECG evidence of conduction disease and 58 (0.9%) experienced a hospitalization with AV block. Older age (hazard ratio [HR] per 5-year increment, 1.34; 95% CI, 1.16-1.54; P CONCLUSIONS AND RELEVANCE In this analysis of data from a population-based cohort study, suboptimal blood pressure and fasting glucose level were associated with AV block. These results suggest that a large proportion of AV blocks are assocated with these risk factors, even after adjusting for other major adverse coronary events.
  • Baglioni, Chiara; Altena, Ellemarije; Bjorvatn, Bjørn; Blom, Kerstin; Bothelius, Kristoffer; Devoto, Alessandra; Espie, Colin A.; Frase, Lukas; Gavriloff, Dimitri; Tuuliki, Hion; Hoflehner, Andrea; Hoegl, Birgit; Holzinger, Brigitte; Järnefelt, Heli; Jernelöv, Susanna; Johann, Anna F.; Lombardo, Caterina; Nissen, Christoph; Palagini, Laura; Peeters, Geert; Perlis, Michael L.; Posner, Donn; Schlarb, Angelika; Spiegelhalder, Kai; Wichniak, Adam; Riemann, Dieter (2020)
    Insomnia, the most prevalent sleep disorder worldwide, confers marked risks for both physical and mental health. Furthermore, insomnia is associated with considerable direct and indirect healthcare costs. Recent guidelines in the US and Europe unequivocally conclude that cognitive behavioural therapy for insomnia (CBT‐I) should be the first‐line treatment for the disorder. Current treatment approaches are in stark contrast to these clear recommendations, not least across Europe, where, if any treatment at all is delivered, hypnotic medication still is the dominant therapeutic modality. To address this situation, a Task Force of the European Sleep Research Society and the European Insomnia Network met in May 2018. The Task Force proposed establishing a European CBT‐I Academy that would enable a Europe‐wide system of standardized CBT‐I training and training centre accreditation. This article summarizes the deliberations of the Task Force concerning definition and ingredients of CBT‐I, preconditions for health professionals to teach CBT‐I, the way in which CBT‐I should be taught, who should be taught CBT‐I and to whom CBT‐I should be administered. Furthermore, diverse aspects of CBT‐I care and delivery were discussed and incorporated into a stepped‐care model for insomnia.