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  • Loukola, Anu; Buchwald, Jadwiga; Gupta, Richa; Palviainen, Teemu; Hallfors, Jenni; Tikkanen, Emmi; Korhonen, Tellervo; Ollikainen, Miina; Sarin, Antti-Pekka; Ripatti, Samuli; Lehtimaki, Terho; Raitakari, Olli; Salomaa, Veikko; Rose, Richard J.; Tyndale, Rachel F.; Kaprio, Jaakko (2015)
    Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism. Our objective was to use nicotine metabolite ratio (NMR), an established biomarker of nicotine metabolism rate, in a genome-wide association study (GWAS) to identify novel genetic variants influencing nicotine metabolism. A heritability estimate of 0.81 (95% CI 0.70-0.88) was obtained for NMR using monozygotic and dizygotic twins of the FinnTwin cohort. We performed a GWAS in cotinine-verified current smokers of three Finnish cohorts (FinnTwin, Young Finns Study, FIN-RISK2007), followed by a meta-analysis of 1518 subjects, and annotated the genome-wide significant SNPs with methylation quantitative loci (meQTL) analyses. We detected association on 19q13 with 719 SNPs exceeding genome-wide significance within a 4.2 Mb region. The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Other interesting genes with genome-wide significant signals included CYP2B6, CYP2A7, EGLN2, and NUMBL. Conditional analyses revealed three independent signals on 19q13, all located within or in the immediate vicinity of CYP2A6. A genetic risk score constructed using the independent signals showed association with smoking quantity (p = 0.0019) in two independent Finnish samples. Our meQTL results showed that methylation values of 16 CpG sites within the region are affected by genotypes of the genome-wide significant SNPs, and according to causal inference test, for some of the SNPs the effect on NMR is mediated through methylation. To our knowledge, this is the first GWAS on NMR. Our results enclose three independent novel signals on 19q13.2. The detected CYP2A6 variants explain a strikingly large fraction of variance (up to 31%) in NMR in these study samples. Further, we provide evidence for plausible epigenetic mechanisms influencing NMR.
  • Kekkonen, Riina A.; Holma, Reetta; Hatakka, Katja; Suomalainen, Tarja; Poussa, Tuija; Adlercreutz, Herman; Korpela, Riitta (2011)
  • Terevnikov, Viacheslav; Stenberg, Jan-Henry; Tiihonen, Jari; Burkin, Mark; Joffe, Grigori (2017)
    Aim: Sexual dysfunction, common in schizophrenia, may be further exaggerated by antipsychotics, especially those of First Generation (FGAs), and antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRs). Mirtazapine, an antidepressant characterized by its different action mechanism compared with that of the majority of other antidepressants, may improve SSRI-induced sexual dysfunction in patients with depression. It is unknown, however, whether mirtazapine improves sexual functioning in schizophrenia.Methods: This study randomly assigned FGA-treated patients with schizophrenia to receive either an add-on mirtazapine (n=20) or a placebo (n=19) for 6 weeks. Sexual functioning was prospectively measured using five relevant items from the Udvalg for Kliniske Undersogelser side-effect rating scale (UKU-SERS).Results: Orgasmic function improved with statistical significance in the mirtazapine group (p=.03), with no changes in any other sexual functions in either group.Conclusion: Add-on mirtazapine appears to relieve orgasmic dysfunction in FGA-treated patients with schizophrenia.
  • Mankinen, Petri; Lundström, Tuomas; Soini, Erkki; Sumelahti, Marja-Liisa; Ruutiainen, Juhani; Niskala, Ulla; Järvinen, Elina (2020)
    Introduction Cost assessment modelling (CAM) of treatments in highly active relapsing multiple sclerosis was conducted. Methods The CAM was developed using the R programming language. The PICOSTEPS health technology assessment framework was applied in the CAM. Modelled patients were 280 adults with highly active relapsing multiple sclerosis eligible for disease-modifying treatment. Intervention was cladribine tablets, a new and reimbursed oral treatment for highly active relapsing multiple sclerosis in Finland. Comparators included fingolimod, the most used oral reimbursed treatment for the highly active disease, and natalizumab, the most used intravenous treatment, and a treatment mix (80% use fingolimod, 20% use natalizumab) in Finland. Outcomes presented expected annual and cumulative drug-associated costs in the overall population and per patient. Setting was modelled public specialist care in Finland. Time was set to 4 years, without discounting. Effects covered expected drug-associated costs (screening, acquisition, administration, monitoring, adverse events, travelling, productivity). Perspective was a limited societal perspective. Sensitivity analyses regarding all PICOSTEPS components were conducted. Results Cladribine tablets were projected to be cost saving in comparison to fingolimod, natalizumab and treatment mix. The respective modelled savings were euro4,598,742, euro16,249,701 and euro6,928,934 in the overall population, and euro16,424, euro58,035 and euro24,746 per patient, respectively, during the 4 years. The most important cost driver was drug costs, representing 96.3%, 96.0% and 83.4% of modelled costs associated with cladribine tablets, fingolimod and natalizumab, respectively. Cladribine tablets sustained their affordability in the sensitivity analyses. From the perspective of health care payer, cladribine tablets' savings were projected to be euro4,514,509, euro15,145,366 and euro6,640,680 in the overall population, and euro16,123, euro54,091 and euro23,717 per patient in comparison to fingolimod, natalizumab and treatment mix, respectively. Conclusion Based on the CAM, cladribine tablets were projected to robustly save modelled drug-associated costs in comparison to fingolimod, natalizumab and their mix in Finland.
  • EFSA Panel Dietetic Prod Nutr; Heinonen, Marina (2017)
    Following an application from Suomen Terveysravinto Oy, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Finland, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to curcumin and normal functioning of joints. The food that is proposed as the subject of the health claim is curcumin. The Panel considers that curcumin is sufficiently characterised. The claimed effect proposed by the applicant is 'normal functioning of joints by reducing the biomarkers of inflammation'. The target population proposed by the applicant is the general population. Upon a request from EFSA to clarify whether the claimed effect is related to the normal function of joints or rather to the reduction of inflammation, the applicant did not address this issue in the reply. The Panel assumes that the claimed effect refers to the maintenance of joint function. The Panel considers that maintenance of joint function is a beneficial physiological effect. The Panel considers that no conclusions can be drawn from 15 human intervention studies conducted in patients with osteoarthritis or rheumatoid arthritis and from one study in obese subjects on serum cytokines for the scientific substantiation of the claim. In the absence of evidence for an effect of curcumin on the normal function of joints in humans, the results of the human studies on curcumin pharmacokinetics, safety and mechanistic studies, the animal studies and the in vitro studies submitted by the applicant cannot be used as a source of data for the scientific substantiation of the claim. The Panel concludes that a cause and effect relationship has not been established between the consumption of curcumin and maintenance of joint function. (C) 2017 European Food Safety Authority.
  • Tuomikoski, Pauliina; Salomaa, Veikko; Havulinna, Aki; Airaksinen, Juhani; Ketonen, Matti; Koukkunen, Heli; Ukkola, Olavi; Kesaniemi, Y. Antero; Lyytinen, Heli; Ylikorkala, Olavi; Mikkola, Tomi S. (2016)
    Objectives: The role of postmenopausal hormone therapy (HT) in the incidence of acute coronary syndrome (ACS) has been studied extensively, but less is known of the impact of HT on the mortality risk due to an ACS. Study design and main outcome measures: We extracted from a population-based ACS register, FINAMI, 7258 postmenopausal women with the first ACS. These data were combined with HT use data from the National Drug Reimbursement Register; 625 patients (9%) had used various HT regimens. The death risks due to ACS before admission to hospital, 2-28, or 29-365 days after the incident ACS were compared between HT users and non-users with logistic regression analyses. Results: In all follow-up time points, the ACS death risks in HT ever-users were smaller compared to non-users. Of women with FIT ever use, 42% died within one year as compared with 52% of non-users (OR 0.62, p <0.001). Most deaths (84%) occurred within 28 days after the ACS, and in this group 36% of women with ever use of FIT (OR 0.73, p = 0.002) and 30% of women with >= 5 year FIT use (OR 0.54, p <0.001) died as compared to 43% of the non-users. Age 60 years at the HT initiation was accompanied with similar reductions in ACS mortality risk. Conclusions: Postmenopausal HT use is accompanied with reduced mortality risk after primary ACS. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Laulajainen-Hongisto, Anu; Aarnisalo, Antti A.; Jero, Jussi (2016)
    Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children.
  • Fokkens, Wytske J.; Lund, Valerie J.; Hopkins, Claire; Hellings, Peter W.; Kern, Robert; Reitsma, Sietze; Toppila-Salmi, Sanna; Bernal-Sprekelsen, Manuel; Mullol, Joaquim; Alobid, Isam; Anselmo-Lima, Wilma Terezinha; Bachert, Claus; Baroody, Fuad; von Buchwald, Christian; Cervin, Anders; Cohen, Noam; Constantinidis, Jannis; De Gabory, Ludovic; Desrosiers, Martin; Diamant, Zuzana; Douglas, Richard G.; Gevaert, Philippe H.; Hafner, Anita; Harvey, Richard J.; Joos, Guy F.; Kalogjera, Livije; Knill, Andrew; Kocks, Janwillem H.; Landis, Basile N.; Limpens, Jacqueline; Lebeer, Sarah; Lourenco, Olga; Matricardi, Paolo M.; Meco, Cem; O'Mahony, Liam; Philpott, Carl M.; Ryan, Dermot; Schlosser, Rodney; Senior, Brent; Smith, Timothy L.; Teeling, Thijs; Tomazic, Peter Valentin; Wang, De Yun; Wang, Dehui; Zhang, Luo; Agius, Adrian M.; Ahlstrom-Emanuelsson, Cecilia; Alabri, Rashid; Albu, Silviu; Alhabash, Saied; Aleksic, Aleksandra; Aloulah, Mohammad; Al-Qudah, Mohannad; Alsaleh, Saad; Baban, Muaid Aziz; Baudoin, Tomislav; Balvers, Tijmen; Battaglia, Paolo; Bedoya, Juan David; Beule, Achim; Bofares, Khaled M.; Braverman, Itzhak; Brozek-Madry, Eliza; Byaruhanga, Richard; Callejas, Claudio; Carrie, Sean; Caulley, Lisa; Chussi, Desderius; de Corso, Eugenio; Coste, Andre; El Hadi, Usama; Elfarouk, Ahmed; Eloy, Philippe H.; Farrokhi, Shokrollah; Felisati, Giovanni; Ferrari, Michel D.; Fishchuk, Roman; Grayson, Jessica W.; Goncalves, Paulo M.; Grdinic, Boris; Grgic, Velimir; Hamizan, Aneeza W.; Heinichen, Julio V.; Husain, Salina; Ping, Tang Ing; Ivaska, Justinas; Jakimovska, Frodita; Jovancevic, Ljiljana; Kakande, Emily; Kamel, Reda; Karpischenko, Sergei; Kariyawasam, Harsha H.; Kawauchi, Hideyuki; Kjeldsen, Anette; Klimek, Ludger; Krzeski, Antoni; Barsova, Gabriela Kopacheva; Kim, Sung Wam; Lal, Devyani; Letort, Jose J.; Lopatin, Andrey; Mahdjoubi, Abdelhak; Mesbahi, Alireza; Netkovski, Jane; Tshipukane, Dieudonne Nyenbue; Obando-Valverde, Andres; Okano, Mitsuhiro; Onerci, Metin; Ong, Yew Kwang; Orlandi, Richard; Otori, Nobuyoshi; Ouennoughy, Kheir; Ozkan, Muge; Peric, Aleksandar; Plzak, Jan; Prokopakis, Emmanuel; Prepageran, Nerayanan; Psaltis, Alkis; Pugin, Benoit; Raftopulos, Marco; Rombaux, Philippe; Riechelmann, Herbert; Sahtout, Semia; Sarafoleanu, Caius-Codrut; Searyoh, Kafui; Rhee, Chae-Seo; Shi, Jianbo; Shkoukani, Mahdi; Shukuryan, Arthur K.; Sicak, Marian; Smyth, David; Snidvongs, Kornkiat; Kosak, Tanja Soklic; Stjarne, Par; Sutikno, Budi; Steinsvag, Sverre; Tantilipikorn, Pongsakorn; Thanaviratananich, Sanguansak; Thuy Tran,; Urbancic, Jure; Valiulis, Arunas; de Aparicio, Carolina Vasquez; Vicheva, Dilyana; Virkkula, Paula M.; Vicente, Gil; Voegels, Richard; Wagenmann, Martin; Wardani, Retno S.; Welge-Lussen, Antje; Witterick, Ian; Wright, Erin; Zabolotniy, Dmytro; Zsolt, Bella; Zwetsloot, Casper P. (2020)
    The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise. The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included.
  • Moore, Andrew; Derry, Sheena; Eccleston, Christopher; Kalso, Eija (2013)
  • Knobler, R.; Berlin, G.; Calzavara-Pinton, P.; Greinix, H.; Jaksch, P.; Laroche, L.; Ludvigsson, J.; Quaglino, P.; Reinisch, W.; Scarisbrick, J.; Schwarz, T.; Wolf, P.; Arenberger, P.; Assaf, C.; Bagot, M.; Barr, M.; Bohbot, A.; Bruckner-Tuderman, L.; Dreno, B.; Enk, A.; French, L.; Gniadecki, R.; Gollnick, H.; Hertl, M.; Jantschitsch, C.; Jung, A.; Just, U.; Klemke, C. -D.; Lippert, U.; Luger, T.; Papadavid, E.; Pehamberger, H.; Ranki, A.; Stadler, R.; Sterry, W.; Wolf, I. H.; Worm, M.; Zic, J.; Zouboulis, C. C.; Hillen, U. (2014)
  • Glinatsi, Daniel; Heiberg, Marte S.; Rudin, Anna; Nordstrom, Dan; Haavardsholm, Espen A.; Gudbjornsson, Bjorn; Ostergaard, Mikkel; Uhlig, Till; Grondal, Gerdur; Horslev-Petersen, Kim; van Vollenhoven, Ronald; Hetland, Merete L. (2017)
    Background: New targeted therapies and improved treatment strategies have dramatically improved the outcomes of patients with rheumatoid arthritis (RA). However, it is unknown whether different early aggressive interventions can induce stable remission or a low-active disease state that can be maintained with conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy, and whether they differ in efficacy and safety. The Nordic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) study will assess and compare (1) the proportion of patients who achieve remission in a head-to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. Methods/design: In a pragmatic, 80-160-week, multicenter, randomized, open-label, assessor-blinded, phase 4 study, 800 patients with early RA (symptom duration less than 24 months) are randomized 1: 1: 1: 1 to one of four different treatment arms: (1) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i. a. glucocorticoids (arm 1A) or methotrexate + prednisolone p.o. (arm 1B), (2) methotrexate + certolizumab-pegol, (3) methotrexate + abatacept, or (4) methotrexate + tocilizumab. The primary clinical endpoint is the proportion of patients reaching Clinical Disease Activity Index (CDAI) remission at week 24. Patients in stable remission over 24 consecutive weeks enter part 2 of the study earliest after 48 weeks. Patients not achieving sustained CDAI remission over 24 consecutive weeks, exit the study after 80 weeks. In part 2, patients are re-randomized to two different de-escalation strategies, either immediate or delayed (after 24 weeks) tapering, followed by cessation of study medication. All patients remain on stable doses of methotrexate. The primary clinical endpoint in part 2 is the proportion of patients in remission (CDAI Discussion: NORD-STAR is the first investigator-initiated, randomized, early RA trial to compare (1) csDMARD and three different bDMARD therapies head to head and (2) two different de-escalation strategies. The trial has the potential to identify which treatment strategy to apply in early RA to achieve the best possible outcomes for both patients and society.
  • Carlson, Emily; Saarikallio, Suvi; Toiviainen, Petri; Bogert, Brigitte; Kliuchko, Marina; Brattico, Elvira (2015)
    Music therapists use guided affect regulation in the treatment of mood disorders. However, self-directed uses of music in affect regulation are not fully understood. Some uses of music may have negative effects on mental health, as can non music regulation strategies, such as rumination. Psychological testing and functional magnetic resonance imaging (fMRI) were used explore music listening strategies in relation to mental health. Participants (n = 123) were assessed for depression, anxiety and Neuroticism, and uses of Music in Mood Regulation (MMR). Neural responses to music were measured in the medial prefrontal cortex (mPFC) in a subset of participants (n = 56). Discharge, using music to express negative emotions, related to increased anxiety and Neuroticism in all participants and particularly in males. Males high in Discharge showed decreased activity of mPFC during music listening compared with those using less Discharge. Females high in Diversion, using music to distract from negative emotions, showed more mPFC activity than females using less Diversion. These results suggest that the use of Discharge strategy can be associated with maladaptive patterns of emotional regulation, and may even have long-term negative effects on mental health. This finding has real-world applications in psychotherapy and particularly in clinical music therapy.
  • Sakalis, Vasileios I.; Karavitakis, Markos; Bedretdinova, Dina; Bach, Thorsten; Bosh, J. L. H. Ruud; Gacci, Mauro; Gratzke, Christian; Herrmann, Thomas R.; Madersbacher, Stephan; Mamoulakis, Charalampos; Tikkinen, Kari A. O.; Gravas, Stavros; Drake, Marcus J. (2017)
    Context: The treatment of nocturia is a key challenge due to the multi-factorial pathophysiology of the symptom and the disparate outcome measures used in research. Objective: To assess and compare available therapy options for nocturia, in terms of symptom severity and quality of life. Evidence acquisition: Medical databases (Embase, Medline, Cochrane Systematic Reviews, Cochrane Central) were searched with no date restriction. Comparative studies were included which studied adult men with nocturia as the primary presentation and lower urinary tract symptoms including nocturia or nocturnal polyuria. Outcomes were symptom severity, quality of life, and harms. Evidence synthesis: We identified 44 articles. Antidiuretic therapy using dose titration was more effective than placebo in relation to nocturnal voiding frequency and duration of undisturbed sleep; baseline serum sodium is a key selection criterion. Screening for hyponatremia (<130 mmol/l) must be undertaken at baseline, after initiation or dose titration, and during treatment. Medications to treat lower urinary tract dysfunction (alpha-1 adrenergic antagonists, 5-alpha reductase inhibitors, phosphodiesterase type 5inhibitor, antimuscarinics, beta-3 agonist, and phytotherapy) were generally not significantly better than placebo in short-term use. Benefits with combination therapies were not consistently observed. Other medications (diuretics, agents to promote sleep, nonsteroidal anti-inflammatories) were sometimes associated with response or quality of life improvement. The recommendations of the Guideline Panel are presented. Conclusions: Issues of trial designmake therapy of nocturia a challenging topic. The range of contributory factors relevant in nocturia makes it desirable to identify predictors of response to guide therapy. Consistent responses were reported for titrated antidiuretic therapy. For other therapies, responses were less certain, and potentially of limited clinical benefit. Patient summary: This review provides an overview of the current drug treatments of nocturia, which is the need to wake at night to pass urine. The symptom can be caused by several different medical conditions, and measuring its severity and impact varies in separate research studies. No single treatment deals with the symptom in all contexts, and careful assessment is essential to make suitable treatment selection. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • Nylund, Lotta; Satokari, Reetta; Nikkila, Janne; Rajilic-Stojanovic, Mirjana; Kalliomaki, Marko; Isolauri, Erika; Salminen, Seppo; de Vos, Willem M. (2013)
  • Morlion, Bart; Schaefer, Michael; Betteridge, Neil; Kalso, Eija (2018)
    Objective: Acute postoperative pain is experienced by the majority of hospitalized patients undergoing surgical procedures, with many reporting inadequate pain relief and/or high levels of dissatisfaction with their pain management. Patient-controlled analgesia (PCA) ensures patient involvement in acute pain control, a key component for implementing a quality management system. This narrative article overviews the clinical evidence for conventional PCA and briefly discusses new, non-invasive PCA systems, namely the sufentanil sublingual tablet system (SSTS) and the fentanyl iontophoretic transdermal system (FITS). Methods: A Medline literature search (patient-controlled analgesia and acute postoperative pain) was conducted to 1 April 2017; results from the main clinical trials are discussed. Additional literature was identified from the reference lists of cited publications. Results: Moderate to low quality evidence supports opioid-based intravenous PCA as an efficacious alternative to non-patient-controlled systemic analgesia for postoperative pain. However, despite the benefits of PCA, conventional intravenous PCA is limited by system-, drug- and human-related issues. The non-invasive SSTS and FITS have demonstrated good efficacy and safety in placebo- and intravenous morphine PCA-controlled trials, and are associated with high patient/healthcare practitioner satisfaction/ease of care ratings and offer early patient mobilization. Conclusions: Evidence-based guidelines for acute postoperative pain management support the use of multimodal regimens in many situations. As effective and safe alternatives to conventional PCA, and with the added benefits of being non-invasive, easy to use and allowing early patient mobilization, the newer PCA systems may complement multimodal approaches, or potentially replace certain regimens, in hospitalized patients with acute postoperative pain.
  • Porsbjerg, Celeste; Ulrik, Charlotte; Skjold, Tina; Backer, Vibeke; Laerum, Birger; Lehman, Sverre; Janson, Crister; Sandstrom, Thomas; Bjermer, Leif; Dahlen, Barbro; Lundback, Bo; Ludviksdottir, Dora; Bjornsdottir, Unnur; Altraja, Alan; Lehtimaki, Lauri; Kauppi, Paula; Karjalainen, Jussi; Kankaanranta, Hannu (2018)
    Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma ('difficult asthma') should undergo systematic assessment, in order to differentiate between true severe asthma, and 'difficult-to-treat' patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care.
  • Sieminski, Mariusz; Szypenbejl, Jacek; Partinen, Eemil (2018)
    The aim of this review was to summarize collected data on the role of orexin and orexin neurons in the control of sleep and blood pressure. Although orexins (hypocretins) have been known for only 20 years, an impressive amount of data is now available regarding their physiological role. Hypothalamic orexin neurons are responsible for the control of food intake and energy expenditure, motivation, circadian rhythm of sleep and wake, memory, cognitive functions, and the cardiovascular system. Multiple studies show that orexinergic stimulation results in increased blood pressure and heart rate and that this effect may be efficiently attenuated by orexinergic antagonism. Increased activity of orexinergic neurons is also observed in animal models of hypertension. Pharmacological intervention in the orexinergic system is now one of the therapeutic possibilities in insomnia. Although the role of orexin in the control of blood pressure is well described, we are still lacking clinical evidence that this is a possibility for a new approach in the treatment of cardiovascular diseases.
  • Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B.; Haanpää, Maija; Hansson, Per; Huellemann, Philipp; Jensen, Troels S.; Freynhagen, Rainer; Kennedy, Jeffrey D.; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S. C.; Segerdahl, Marta; Serra, Jordi; Sindrup, Soren; Sommer, Claudia; Toelle, Thomas; Vollert, Jan; Treede, Rolf-Detlef; German Neuropathic Pain Res Networ; EUROPAIN; NEUROPAIN Consortia (2017)
    Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of painrelated sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profilesmight respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroupswith characteristic sensory profileswere identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combinationwith pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.
  • Cherney, David Z. I.; Cooper, Mark E.; Tikkanen, Ilkka; Pfarr, Egon; Johansen, Odd Erik; Woerle, Hans J.; Broedl, Uli C.; Lund, Soren S. (2018)
    Sodium glucose cotransporter 2 (SGLT2) inhibitors reduce HbA1c, blood pressure, and weight in patients with type 2 diabetes. To investigate the effect of renal function on reductions in these parameters with the SGLT2 inhibitor empagliflozin, we assessed subgroups by baseline estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease) in pooled data from five 24-week trials of 2286 patients with type 2 diabetes randomized to empagliflozin or placebo. Reductions in HbA1c with empagliflozin versus placebo significantly diminished with decreasing baseline eGFR. Reductions in systolic blood pressure (SBP) with empagliflozin were maintained in patients with lower eGFR. The mean placebo-corrected changes from baseline in systolic blood pressure at week 24 with empagliflozin were -3.2 (95% confidence interval -4.9,-1.5) mmHg, -4.0 (-5.4, -2.6) mmHg, -5.5 (-7.6, -3.4) mmHg, and -6.6 (-11.4, -1.8) mmHg in patients with an eGFR of 90 or more, 60 to 89, 30 to 59, and under 30 ml/min/1.73m(2), respectively. Similar trends were observed for diastolic blood pressure. Weight loss with empagliflozin versus placebo tended to be attenuated in patients with a lower eGFR. Results were consistent in a 12-week ambulatory blood pressure monitoring trial in 823 patients with type 2 diabetes and hypertension. Thus, unlike HbA1c reductions, systolic blood pressure and weight reductions with empagliflozin are generally preserved in patients with chronic kidney disease.