Browsing by Subject "EFFICACY"

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  • ARIA Working Grp; Bousquet, J; Pfaar, O; Togias, A; Haahtela, T; Toppila-Salmi, S (2019)
    Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients.
  • Gu, Ying; Lee, Hsi-Ming; Napolitano, Nicole; Clemens, McKenzie; Zhang, Yazhou; Sorsa, Timo; Zhang, Yu; Johnson, Francis; Golub, Lorne M. (2013)
  • Schnitzbauer, Andreas A.; Zuelke, Carl; Graeb, Christian; Rochon, Justine; Bilbao, Itxarone; Burra, Patrizia; de Jong, Koert P.; Duvoux, Christophe; Kneteman, Norman M.; Adam, Rene; Bechstein, Wolf O.; Becker, Thomas; Beckebaum, Susanne; Chazouilleres, Olivier; Cillo, Umberto; Colledan, Michele; Faendrich, Fred; Gugenheim, Jean; Hauss, Johann P.; Heise, Michael; Hidalgo, Ernest; Jamieson, Neville; Koenigsrainer, Alfred; Lamby, Philipp E.; Lerut, Jan P.; Mäkisalo, Heikki; Margreiter, Raimund; Mazzaferro, Vincenzo; Mutzbauer, Ingrid; Otto, Gerd; Pageaux, Georges-Philippe; Pinna, Antonio D.; Pirenne, Jacques; Rizell, Magnus; Rossi, Giorgio; Rostaing, Lionel; Roy, Andre; Sanchez Turrion, Victor; Schmidt, Jan; Troisi, Roberto I.; van Hoek, Bart; Valente, Umberto; Wolf, Philippe; Wolters, Heiner; Mirza, Darius F.; Scholz, Tim; Steininger, Rudolf; Soderdahl, Gunnar; Strasser, Simone I.; Jauch, Karl-Walter; Neuhaus, Peter; Schlitt, Hans J.; Geissler, Edward K. (2010)
  • Niemelä, Tytti M.; Tulamo, Riitta-Mari; Hielm-Björkman, Anna K. (2016)
    Background: Intra-articular inflammation resulting in lameness is a common health problem in horses. Exogenous intra-articular hyaluronic acid has been shown to provide an analgesic effect and reduce pain in equine and human osteoarthritis. High molecular weight non-animal stabilized hyaluronic acid (NASHA) has gained popularity in the treatment of human arthritic conditions due to its long-acting pain-relieving effects. The aim of this study was to compare the response to treatment of lameness localized in the equine metacarpophalangeal joint injected with non-animal stabilized hyaluronic acid (NASHA) and placebo (saline). Twenty-seven clinically lame horses with a positive response to diagnostic intra-articular anaesthesia of the metacarpophalangeal joint and with no, or at most mild, radiographic changes in this joint were included in the study. Horses in the treatment group (n = 14) received 3 mL of a NASHA product intra-articularly, and those in the placebo group (n = 13) received an equivalent volume of sterile 0.9 % saline solution. Results: The change in the lameness score did not significantly differ between NASHA and placebo groups (P = 0.94). Scores in the flexion test improved more in the NASHA group compared with placebo (P = 0.01). The changes in effusion and pain in flexion were similar (P = 0.94 and P = 0.27, respectively) when NASHA and placebo groups were compared. A telephone interview follow-up of the owners three months post-treatment revealed that 14 of the 21 horses (67 %) were able to perform at their previous level of exercise. Conclusions: In the present study, a single IA NASHA injection was not better than a single saline injection for reducing lameness in horses with synovitis or mild osteoarthritis. However, the results of this study indicate that IA NASHA may have some beneficial effects in modifying mild clinical signs but more research is needed to evaluate whether the positive effect documented ie. reduced response in the flexion test is a true treatment effect.
  • Santos, Joao Manuel; Cervera-Carrascon, Victor; Havunen, Riikka; Zafar, Sadia; Siurala, Mikko; Sorsa, Suvi; Anttila, Marjukka; Kanerva, Anna; Hemminki, Akseli (2018)
    Lymphodepleting preconditioning with high-dose chemotherapy is commonly used to increase the clinical efficacy of adoptive T cell therapy (ACT) strategies, however, with severe toxicity for patients. Conversely, oncolytic adenoviruses are safe and, when engineered to express interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-alpha), they can achieve antitumor immunomodulatory effects similar to lymphodepletion. Therefore, we compare the safety and efficacy of such adenoviruses with a cyclophosphamide-and fludarabine- containing lymphodepleting regimen in the setting of ACT. Human adenovirus (Ad5/3-E2F-D24-hTNF-alpha-IRES-hIL-2; TILT-123) replication was studied using a Syrian hamster pancreatic tumor model (HapT1) infused with tumor- infiltrating lymphocytes (TILs). Using the oncolytic virus instead of lymphodepletion resulted in superior efficacy and survival. Immune cells responsive to TNF-alpha IL-2 were studied using an immunocompetent mouse melanoma model (B16. OVA) infused with ovalbumin-specific T (OT-I) cells. Here, the adenovirus approach improved tumor control together with increased intratumoral Th1 cytokine levels and infiltration of CD8+ T cells and CD86+ dendritic cells. Similar to humans, lymphodepleting preconditioning caused severe cytopenias, systemic inflammation, and damage to vital organs. Toxicity was minimal in adenovirus- and OT-Itreated mice. These findings demonstrate that ACT can be effectively facilitated by cytokine-coding adenovirus without requiring lymphodepletion, a rationale being clinically investigated.
  • Sousa-Pinto, Bernardo; Azevedo, Luis Filipe; Sa-Sousa, Ana; Vieira, Rafael Jose; Amaral, Rita; Klimek, Ludger; Czarlewski, Wienczyslawa; Anto, Josep M.; Bedbrook, Anna; Kvedariene, Violeta; Ventura, Maria Teresa; Ansotegui, Ignacio J.; Bergmann, Karl-Christian; Brussino, Luisa; Canonica, G. Walter; Cardona, Victoria; Carreiro-Martins, Pedro; Casale, Thomas; Cecchi, Lorenzo; Chivato, Tomas; Chu, Derek K.; Cingi, Cemal; Costa, Elisio M.; Cruz, Alvaro A.; De Feo, Giulia; Devillier, Philippe; Fokkens, Wytske J.; Gaga, Mina; Gemicioglu, Bilun; Haahtela, Tari; Ivancevich, Juan Carlos; Ispayeva, Zhanat; Jutel, Marek; Kuna, Piotr; Kaidashev, Igor; Kraxner, Helga; Larenas-Linnemann, Desiree E.; Laune, Daniel; Lipworth, Brian; Louis, Renaud; Makris, Michael; Monti, Riccardo; Morais-Almeida, Mario; Moesges, Ralph; Mullol, Joaquim; Odemyr, Mikaela; Okamoto, Yoshitaka; Papadopoulos, Nikolaos G.; Patella, Vincenzo; Nhan Pham-Thi; Regateiro, Frederico S.; Reitsma, Sietze; Rouadi, Philip W.; Samolinski, Boleslaw; Sova, Milan; Todo-Bom, Ana; Taborda-Barata, Luis; Tomazic, Peter Valentin; Toppila-Salmi, Sanna; Sastre, Joaquin; Tsiligianni, Ioanna; Valiulis, Arunas; Wallace, Dana; Waserman, Susan; Yorgancioglu, Arzu; Zidarn, Mihaela; Zuberbier, Torsten; Fonseca, Joao Almeida; Bousquet, Jean; Pfaar, Oliver (2022)
    Background Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real-life studies. Objective To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK-air(R) app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. Methods We assessed the MASK-air(R) data of European users with self-reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales-VASs), and a combined symptom-medication score (CSMS). We applied Bayesian mixed-effects models, with clustering by patient, country and pollen season. Results We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT-tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = -12.1;-2.8), lower VAS Work (average difference = 5.0; 95%CrI = -8.5;-1.5), and a lower CSMS (average difference = 3.7; 95%CrI = -9.3;2.2). When compared to SCIT, SLIT-tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = -17.2;-2.8), lower VAS Work (average difference = 7.8; 95%CrI = -15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = -18.5;0.2). Conclusion In patients with grass pollen allergy, SLIT-tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally-harmonised standards for performing and reporting real-world data in AIT are needed to better understand its 'real-world' effectiveness.
  • Friman, Mari; Kakko, Leila; Constantin, Camelia; Simojoki, Heli; Andersson, Maria A.; Nagy, Szabolcs; Salonen, Heidi; Andersson, Magnus (2019)
    Bacillus anthracis infecting cattle is usually identified based on the typical symptom: sudden death. Bacillus anthracis causing atypical symptoms may remain undiagnosed and represent a potential occupational health hazard for, that is veterinarians and producers, butchers and tanners. In the year 2004, one case of sudden death in a dairy farm in southern Finland was diagnosed as bovine anthrax. Four years later 2008, an atypical case of anthrax was diagnosed in the same holding. The bull was taken to the Production Animal Hospital of the Faculty of Veterinary Medicine, University of Helsinki because of fever, loss of appetite and a symmetrically swollen scrotal sac. Penicillin treatment cured the fever but not the swollen scrotum. Before the intended therapeutic castration, a punctuate consisting of 10 ml fluid collected into a syringe from the scrotal sac was cultivated on blood agar at 37 degrees C. After 24 hr, an almost pure culture of a completely non-hemolytic Bacillus cereus-like bacteria was obtained. The strain was identified as B. anthracis using Ba-specific primers by the Finnish Food Safety Authority (RUOKAVIRASTO). After the diagnosis, the bull was euthanized and destroyed, the personnel were treated with prophylactic antibiotics and the clinic was disinfected. In this particular case, treatment with water, Virkon S and lime seemed to be effective to eliminate endospores and vegetative cells since no relapses of anthrax have occurred in 10 years. This case is the last reported anthrax case in Finland.
  • Kortteenniemi, Aaron; Ortega-Alonso, Alfredo; Javadi, Amir-Homayoun; Tolmunen, Tommi; Ali-Sisto, Toni; Kotilainen, Tuukka; Wikgren, Jan; Karhunen, Leila; Velagapudi, Vidya; Lehto, Soili M. (2020)
    Background Transcranial direct current stimulation (tDCS), a putative treatment for depression, has been proposed to affect peripheral metabolism. Metabolic products from brain tissue may also cross the blood-brain barrier, reflecting the conditions in the brain. However, there are no previous data regarding the effect of tDCS on circulating metabolites. Objective To determine whether five daily sessions of tDCS modulate peripheral metabolites in healthy adult men. Methods This double-blind, randomized controlled trial involved 79 healthy males (aged 20-40 years) divided into two groups, one receiving tDCS (2 mA) and the other sham stimulated. The anode was placed over the left dorsolateral prefrontal cortex and the cathode over the corresponding contralateral area. Venous blood samples were obtained before and after the first stimulation session, and after the fifth stimulation session. Serum levels of 102 metabolites were determined by mass spectrometry. The results were analysed with generalised estimating equations corrected for the family-wise error rate. In addition, we performed power calculations estimating sample sizes necessary for future research. Results TDCS-related variation in serum metabolite levels was extremely small and statistically non-significant. Power calculations indicated that for the observed variation to be deemed significant, samples sizes of up to 11,000 subjects per group would be required, depending on the metabolite of interest. Conclusion Our study found that five sessions of tDCS induced no major effects on peripheral metabolites among healthy men. These observations support the view of tDCS as a safe treatment that does not induce significant changes in the measured peripheral metabolites in healthy male subjects.
  • Aulbach, Matthias Burkard; Knittle, Keegan; van Beurden, Samantha Barbara; Haukkala, Ari; Lawrence, Natalia S. (2021)
    Food Go/No-Go training aims to alter implicit food biases by creating associations between perceiving unhealthy foods and withholding a dominant response. Asking participants to repeatedly inhibit an impulse to approach unhealthy foods can decrease unhealthy food intake in laboratory settings. Less is known about how people engage with app-based Go/No-Go training in real-world settings and how this might relate to dietary outcomes. This pragmatic observational study investigated associations between the number of completed app-based food Go/No-Go training trials and changes in food intake (Food Frequency Questionnaire; FFQ) for different healthy and unhealthy food categories from baseline to one-month follow-up. In total, 1234 participants (m(BMI) = 29 kg/ m2, m(age) = 43years, 69% female) downloaded the FoodT app and completed food-Go/No-Go training at their own discretion (mean number of completed sessions = 10.7, sd = 10.3, range: 1-122). In pre-registered analyses, random-intercept linear models predicting intake of different foods, and controlled for baseline consumption, BMI, age, sex, smoking, metabolic syndrome, and dieting status, revealed small, significant associations between the number of completed training trials and reductions in unhealthy food intake (b = -0.0005, CI95 = [-0.0007;0.0003]) and increases in healthy food intake (b = 0.0003, CI95 = [0.0000; 0.0006]). These relationships varied by food category, and exploratory analyses suggest that more temporally spaced training was associated with greater changes in dietary intake. Taken together, these results imply a positive association between the amount of training completed and beneficial changes in food intake. However, the results of this pragmatic study should be interpreted cautiously, as self-selection biases, motivation and other engagement-related factors that could underlie these associations were not accounted for. Experimental research is needed to rule out these possible confounds and establish causal dose-response relationships between patterns of engagement with food Go/No-Go training and changes in dietary intake.
  • Antti, Andreas; Salava, Alexander; Perälä, Miia; Pelkonen, Anna S.; Mäkelä, Mika J.; Remitz, Anita (2021)
  • Hjortsberg, Catharina; Bergman, Annika; Bjarnason, Anton; Heikkila, Hannele; Rielmgren, Jonas; Svensson, Ake; Tennvall, Gunnel Ragnarson (2011)
  • Nislin, Mari; Pesonen, Henri (2019)
    In this article, we sought to determine the extent to which pre-service and in-service teachers' self-perceived competence is associated with sense of belonging and well-being during special education teacher studies, as well as determine whether there are differences among these factors between pre-service and in-service teachers. These are areas in which there is currently a shortage of research. Our data were collected using a survey with close-ended questions. The respondents consisted of 58 in-service and 29 pre-service teachers, aged 21-56 years. Data were analysed utilising quantitative methods. The findings revealed that the respondents demonstrated generally high levels of engagement and low to moderate levels of burnout. The results further indicated that the respondents reported themselves to be most competent when dealing with children of drug-related family abuse and less competent in working with children with severe disabilities. Although well-being and self-perceived competence were associated, we could not find any association between these factors and the sense of belonging. Given the theoretical and empirical evidence, a deeper understanding of the factors relating to teachers' ability to encounter diverse needs is unquestionably needed. The key findings are discussed in detail, and practical implications for teacher education are given.
  • Matsubara, L. M.; Luna, S. P. L.; Teixeira, L. R.; Castilho, M. S.; Bjorkman, A. H.; Oliveira, H. S.; Anunciacao, L. F. C. (2019)
    We aimed to determine validity, reliability, and sensitivity of Helsinki's chronic pain index (HCPI) and stablish a correlation between HCPI in dogs with hip dysplasia (HD) using pressure sensitive walkway. Forty-owners of dogs with HD and 16 owners of health dogs filled a questionnaire. Dogs with HD were treated with carprofen 4.4mg/ kg (GT n=21) or with placebo (GP n=19), both were administered once a day for 4 weeks. Evaluation was performed by the owners using the questionnaire (HCPI), the Visual Analogue Scale for pain (VASpain) and the VAS for locomotion (VASloc). The evaluation was performed 2 weeks before the treatment began (A1), immediately after treatment (A2), two (S2), four (S4) and two weeks after the end of treatment (S6) and the lameness was evaluated by pressure sensitive walkway. The internal consistency of the data was considered excellent (Cronbach alpha coefficient=0.89). There was a moderate correlation between the HCPI and VASpain. For VASloc the correlation was good. However, there was no difference between treatments, indicating low sensibility. No correlation was observed between pressure sensitive walkway and HCPI. We concluded that the questionnaire has construct and criterion validity, reliability and can be applied in dogs with osteoarthritis in Portuguese-speaking countries.
  • Vanic, Zeljka; Rukavina, Zora; Manner, Suvi; Fallarero, Adyary; Uzelac, Lidija; Kralj, Marijeta; Klaric, Daniela Amidzic; Bogdanov, Anita; Raffai, Timea; Virok, Dezso Peter; Filipovic-Grcic, Jelena; Skalko-Basnet, Natasa (2019)
    Background: Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose: The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods: AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results: Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion: The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.
  • Louvanto, Karolina; Eriksson, Tiina; Gray, Penelope; Apter, Dan; Baussano, Iacopo; Bly, Anne; Harjula, Katja; Heikkila, Kaisa; Hokkanen, Mari; Huhtinen, Leila; Ikonen, Marja; Karttunen, Heidi; Nummela, Mervi; Soderlund-Strand, Anna; Veivo, Ulla; Dillner, Joakim; Elfstöm, Miriam; Nieminen, Pekka; Lehtinen, Matti (2020)
    Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life-years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992-1994 birth-cohorts (30,139 females) were invited to a community-randomized HPV16/18-vaccination trial. A total of 9,482 female trial participants received HPV16/18-vaccination in 2007-2009 at age of 13-15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014-2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high-risk HPV types were: 0.5% (53/1,000 follow-up years, 10(4)) and 25% (2,530/10(4)) in the frequently screened Arm 1; 0.2% (23/10(4)) and 24% (2,413/10(4)) in the infrequently screened Arm 2; and 3.1% (304/10(4)) and 23% (2,284/10(4)) in the safety Arm 3. Corresponding prevalence of HSIL/ASC-H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former.
  • Eriksson, M.; Reichardt, P.; Joensuu, H.; Krarup-Hansen, A.; Hagberg, O.; Hohenberger, P.; Hagberg, H.; Hansson, L.; Foukakis, T.; Pulkkanen, K.; Bauer, S.; Goplen, D.; Rossen, P. Blach; Hall, K. Sundby (2021)
    Background: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. Patients and methods: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were >= 18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission thorn partial remission thorn stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. Results: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. Conclusion: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.
  • Radun, Igor; Olivier, Jake (2018)
    Bicycle helmet legislation (BHL) in Finland went into effect in January 2003 and applies to cyclists of all ages. There are no mechanisms to fine cyclists riding without a helmet; however, helmet wearing rates are 64% in Helsinki and 42% across Finland. Our aim was to discuss possible effects of BHL on cycling in Finland. We used data from the 1998/1999, 2004/2005 and 2010/2011 Finnish National Travel Surveys. Data across three surveys suggest cycling has declined from before to after BHL. In a 2004/2005 survey, however, only 0.063% (95% CI: 0.02-0.10%) of responders identified helmet use as their most important obstacle to cycling. It is unlikely BHL is a causal factor in the downward trend in Finnish cycling. Lack of cycling infrastructure and concerns for safety are much more common reasons given. (C) 2018 Elsevier Ltd. All rights reserved.
  • Fontana, Flavia; Fusciello, Manlio; Groeneveldt, Christianne; Capasso, Cristian; Chiaro, Jacopo; Feola, Sara; Liu, Zehua; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni; Cerullo, Vincenzo; Santos, Hélder A. (2019)
    Recent approaches in the treatment of cancer focus on involving the immune system to control the tumor growth. The administration of immunotherapies, like checkpoint inhibitors, has shown impressive results in the long term survival of patients. Cancer vaccines are being investigated as further tools to prime tumor-specific immunity. Biomaterials show potential as adjuvants in the formulation of vaccines, and biomimetic elements derived from the membrane of tumor cells may widen the range of antigens contained in the vaccine. Here, we show how mice presenting an aggressive melanoma tumor model treated twice with the complete nanovaccine formulation showed control on the tumor progression, while in a less aggressive model, the animals showed remission and control on the tumor progression, with a modification in the immunological profile of the tumor microenvironment. We also prove that co-administration of the nanovaccine together with a checkpoint inhibitor increases the efficacy of the treatment (87.5% of the animals responding, with 2 remissions) compared to the checkpoint inhibitor alone in the B16.OVA model. Our platform thereby shows potential applications as a cancer nanovaccine in combination with the standard clinical care treatment for melanoma cancers.
  • Choueiri, Toni K.; Escudier, Bernard; Powles, Thomas; Tannir, Nizar M.; Mainwaring, Paul N.; Rini, Brian I.; Hammers, Hans J.; Donskov, Frede; Roth, Bruce J.; Peltola, Katriina; Lee, Jae Lyun; Heng, Daniel Y. C.; Schmidinger, Manuela; Agarwal, Neeraj; Sternberg, Cora N.; McDermott, David F.; Aftab, Dana T.; Hessel, Colin; Old, Christian Scheff; Schwab, Gisela; Hutson, Thomas E.; Pal, Sumanta; Motzer, Robert J.; METEOR Investigators (2016)
    Background Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment. Here, we report the final overall survival results from this study based on an unplanned second interim analysis. Methods In this open-label, randomised phase 3 trial, we randomly assigned (1:1) patients aged 18 years and older with advanced or metastatic clear-cell renal cell carcinoma, measurable disease, and previous treatment with one or more VEGFR tyrosine-kinase inhibitors to receive 60 mg cabozantinib once a day or 10 mg everolimus once a day. Randomisation was done with an interactive voice and web response system. Stratification factors were Memorial Sloan Kettering Cancer Center risk group and the number of previous treatments with VEGFR tyrosine-kinase inhibitors. The primary endpoint was progression-free survival as assessed by an independent radiology review committee in the first 375 randomly assigned patients and has been previously reported. Secondary endpoints were overall survival and objective response in all randomly assigned patients assessed by intention-to-treat. Safety was assessed per protocol in all patients who received at least one dose of study drug. The study is closed for enrolment but treatment and follow-up of patients is ongoing for long-term safety evaluation. This trial is registered with, number NCT01865747. Findings Between Aug 8, 2013, and Nov 24, 2014, 658 patients were randomly assigned to receive cabozantinib (n=330) or everolimus (n=328). The median duration of follow-up for overall survival and safety was 18.7 months (IQR 16.1-21.1) in the cabozantinib group and 18.8 months (16.0-21.2) in the everolimus group. Median overall survival was 21.4 months (95% CI 18.7-not estimable) with cabozantinib and 16.5 months (14.7-18.8) with everolimus (hazard ratio [HR] 0.66 [95% CI 0.53-0.83]; p=0.00026). Cabozantinib treatment also resulted in improved progression-free survival (HR 0.51 [95% CI 0.41-0.62]; p Interpretation Treatment with cabozantinib increased overall survival, delayed disease progression, and improved the objective response compared with everolimus. Based on these results, cabozantinib should be considered as a new standard-of-care treatment option for previously treated patients with advanced renal cell carcinoma. Patients should be monitored for adverse events that might require dose modifications.
  • Pokorney, Sean D.; Piccini, Jonathan P.; Stevens, Susanna R.; Patel, Manesh R.; Pieper, Karen S.; Halperin, Jonathan L.; Breithardt, Gunter; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.; ROCKET AF Steering Comm; Kaste, Markku (2016)
    Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereas