Browsing by Subject "CLINICAL-TRIALS"

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  • Salminen, Liina; Nadeem, Nimrah; Jain, Shruti; Grènman, Seija; Carpén, Olli; Hietanen, Sakari; Oksa, Sinikka; Lamminmäki, Urpo; Pettersson, Kim; Gidwani, Kamlesh; Huhtinen, Kaisa; Hynninen, Johanna (2020)
    Objective. Cancer antigen 125 (CM 25) is generally considered the gold standard of biomarkers in the diagnosis and monitoring of high grade serous ovarian carcinoma (HGSC). We recently reported, that two CM 25 glycoforms (CA125-STn and CA125-MGL) have a high specificity to HGSC and further hypothesized, that these cancer specific glycoforms are feasible candidates as biomarkers in HGSC treatment and follow up. Methods. Our cohort consisted of 122 patients diagnosed with HGSC. Serum samples were collected longitudinally at the time of diagnosis, during treatment and follow up. Serum levels of CA125, CM 25-STn and CA125MGL were determined and compared or correlated with different end points (tumor load assessed intraoperatively, residual disease, treatment response, progression free survival). Results. Serum CA125-STn levels at diagnosis differentiated patients with low tumor load and high tumor load (p = 0,030), indicating a favorable detection of tumor volume. Similarly, the CA125-STn levels at diagnosis were significantly lower in patients with subsequent complete cytoreduction than in patients with suboptimal cytoreduction (p = 0,025). Conventional CA125 did not differentiate these patients (p = 0,363 and p = 0,154). The CA125-STn nadir value predicted the progression free survival of patients. The detection of disease relapse was improved with CA125-STn, which presented higher fold increase in 80,0% of patients and earlier increase in 37,0% of patients. Conclusions. CA125-STn showed promise as a useful biomarker in the monitoring and follow up of patients with HGSC utilizing a robust and affordable technique. Our findings are topical as a suitable indicator of tumor load facilitates patient selection in an era of new targeted therapies. (C) 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://
  • Pettilä, Ville; Kyhälä, Lea; Kylänpää, Marja-Leena; Leppäniemi, Ari; Tallgren, Minna; Markkola, Antti Thor Olavi; Puolakkainen, Pauli; Repo, Heikki; Kemppainen, Esko (2010)
  • Haywood, Kirstie L.; Pearson, Nathan; Morrison, Laurie J.; Castren, Maaret; Lilja, Gisela; Perkins, Gavin D. (2018)
    Aim: High quality evidence of out-of-hospital cardiac arrest (OHCA) survivors' health-related quality of life (HRQoL) can measure the long-term impact of CA. The aim of this study was to critically appraise the evidence of psychometric quality and acceptability of measures used in the assessment of HRQoL in cardiac arrest survivors. Methods: Systematic literature searches (2004-2017) and named author searches to identify articles pertaining to the measurement of HRQoL. Data on study quality, measurement and practical properties were extracted and assessed against international standards. Results: From 356 reviewed abstracts, 69 articles were assessed in full. 25 provided evidence for 10 measures of HRQoL: one condition-specific; three generic profile measures; two generic index; and four utility measures. Although limited, evidence for measurement validity was strongest for the HUI3 and SF-36. However, evidence for reliability, content validity, responsiveness and interpretability and acceptability was generally limited or not available in the CA population for all measures. Conclusions: This review has demonstrated that a measure of quality of life specific to OHCA survivors is not available. Limited evidence of validity exists for one utility measure - the HUI3 - and a generic profile - the SF-36. Robust evidence of the quality and acceptability of HRQoL measures in OHCA was limited or not available. Future collaborative research must seek to urgently establish the relevance and acceptability of these measures to OHCA survivors, to establish robust evidence of essential measurement and practical properties over the short and long-term, and to inform future HRQoL assessment in the OHCA population. (C) 2017 Elsevier B.V. All rights reserved.
  • Stephen, Ruth; Liu, Yawu; Ngandu, Tiia; Rinne, Juha O.; Kemppainen, Nina; Parkkola, Riitta; Laatikainen, Tiina; Paajanen, Teemu; Hanninen, Tuomo; Strandberg, Timo; Antikainen, Riitta; Tuomilehto, Jaakko; Keinanen Kiukaanniemi, Sirkka; Vanninen, Ritva; Helisalmi, Seppo; Levalahti, Esko; Kivipelto, Miia; Soininen, Hilkka; Solomon, Alina (2017)
    Background: CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile. Objectives: This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures. Methods: FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation. Results: Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (beta- coefficient -0.29, p = 0.001) and hippocampal volume (beta- coefficient -0.28, p = 0.003), lower cortical thickness (beta-coefficient -0.19, p = 0.042), and poorer cognition (beta-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p <0.001). Higher CAIDE Dementia Risk Score including APOE genotype was additionally related to more pronounced MTA (OR 1.15,95% CI 1.00-1.30). No associations were found with periventricular WML or amyloid accumulation. Conclusions: The CAIDE Dementia Risk Score was related to indicators of cerebrovascular changes and neurodegeneration on MRI, and cognition. The lack of association with brain amyloid accumulation needs to be verified in studies with larger sample sizes.
  • Friedland, Barbara A.; Stoner, Marie; Chau, Michelle M.; Plagianos, Marlena Gehret; Govender, Sumen; Morar, Neetha; Altini, Lydia; Skoler-Karpoff, Stephanie; Ahmed, Khatija; Ramjee, Gita; Monedi, Constance; Maguire, Robin; Lähteenmäki, Pekka (2016)
    A randomized, placebo-controlled, efficacy trial of Carraguard was unable to demonstrate a reduction in women's risk of HIV infection, which may have been due, in part, to low adherence (gel used in 42 % of vaginal sex acts, on average). A secondary analysis was undertaken to understand baseline factors associated with high adherence (gel used in aeyen85 % of sex acts). Women who reported aeyen1 vaginal sex act, returned aeyen1 opened applicator, and had aeyen1 conclusive post-enrollment HIV test (N = 5990) were included. Adherence was estimated as the ratio of average weekly applicator insertions (based on a dye stain assay indicating vaginal insertion)/average weekly sex acts (by self-report). Multivariate logistic regression modeling indicated that coital frequency, site, contraception, and partner age difference had a significant impact on adherence. Women reporting > 1 and aecurrency sign2 vaginal sex acts per week, on average, were half as likely to be adherent as those reporting 1 vaginal sex act per week or less [adjusted odds ratio (AOR): 0.48; 95 % CI 0.38-0.61]; women from the Western Cape had one-third the odds of being adherent compared to women from KZN (AOR: 0.31; 95 % CI 0.23-0.41); compared to women using injectable contraception, women using any other or no method were more likely to be adherent (AOR: 1.30; 95 % CI 1.04-1.63); and women who had a larger age gap from their partners were more likely to be adherent (AOR: 1.03; 95 % CI 1.01-1.05; p = 0.001). Despite low adherence, overall, 13 % of participants achieved nearly perfect adherence, indicating a potential niche for a coitally dependent microbicide. More research is needed on the impact of sexual patterns and HIV risk perception on product acceptability and adherence to improve counseling in ongoing trials and when products are eventually introduced.
  • Kanerva, Anna; Koski, Anniina; Liikanen, Ilkka; Oksanen, Minna; Joensuu, Timo; Hemminki, Otto; Palmgren, Juni; Hemminki, Kari; Hemminki, Akseli (2015)
  • Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M.; Wilkman, Erika; Perner, Anders; Takala, Jukka (2016)
    The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.
  • Rantonen, J.; Karppinen, J.; Vehtari, A.; Luoto, S.; Viikari-Juntura, E.; Hupli, M.; Malmivaara, A.; Taimela, S. (2016)
    Background: Evidence shows that low back specific patient information is effective in sub-acute low back pain (LBP), but effectiveness and cost-effectiveness (CE) of information in early phase symptoms is not clear. We assessed effectiveness and CE of patient information in mild LBP in the occupational health (OH) setting in a quasi-experimental study. Methods: A cohort of employees (N = 312, aged Results: Compared to NC, the Booklet reduced HC costs by 196(sic) and SA by 3.5 days per year. In 81 % of the bootstrapped cases the Booklet was both cost saving and effective on SA. Compared to NC, in the Combined arm, the figures were 107(sic), 0.4 days, and 54 %, respectively. PHI decreased in both interventions. Conclusions: Booklet information alone was cost-effective in comparison to natural course of mild LBP. Combined information reduced HC costs. Both interventions reduced physical impairment. Mere booklet information is beneficial for employees who report mild LBP in the OH setting, and is also cost saving for the health care system.
  • van Zanten, Sophie E. M. Veldhuijzen; Baugh, Joshua; Chaney, Brooklyn; De Jongh, Dennis; Aliaga, Esther Sanchez; Barkhof, Frederik; Noltes, Johan; De Wolf, Ruben; Van Dijk, Jet; Cannarozzo, Antonio; Damen-Korbijn, Carin M.; Lieverst, Jan A.; Colditz, Niclas; Hoffmann, Marion; Warmuth-Metz, Monika; Bison, Brigitte; Jones, David T. W.; Sturm, Dominik; Gielen, Gerrit H.; Jones, Chris; Hulleman, Esther; Calmon, Raphael; Castel, David; Varlet, Pascale; Giraud, Geraldine; Slavc, Irene; Van Gool, Stefaan; Jacobs, Sandra; Jadrijevic-Cvrlje, Filip; Sumerauer, David; Nysom, Karsten; Pentikäinen, Virve; Kivivuori, Sanna-Maria; Leblond, Pierre; Entz-Werle, Natasha; von Bueren, Andre O.; Kattamis, Antonis; Hargrave, Darren R.; Hauser, Peter; Garami, Miklos; Thorarinsdottir, Halldora K.; Pears, Jane; Gandola, Lorenza; Rutkauskiene, Giedre; Janssens, Geert O.; Torsvik, Ingrid K.; Perek-Polnik, Marta; Gil-da-Costa, Maria J.; Zheludkova, Olga; Shats, Liudmila; SIOPE DIPG Network (2017)
    Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.
  • Horne, Hisani N.; Oh, Hannah; Sherman, Mark E.; Palakal, Maya; Hewitt, Stephen M.; Schmidt, Marjanka K.; Milne, Roger L.; Hardisson, David; Benitez, Javier; Blomqvist, Carl; Bolla, Manjeet K.; Brenner, Hermann; Chang-Claude, Jenny; Cora, Renata; Couch, Fergus J.; Cuk, Katarina; Devilee, Peter; Easton, Douglas F.; Eccles, Diana M.; Eilber, Ursula; Hartikainen, Jaana M.; Heikkilä, Paivi; Holleczek, Bernd; Hooning, Maartje J.; Jones, Michael; Keeman, Renske; Mannermaa, Arto; Martens, John W. M.; Muranen, Taru A.; Nevanlinna, Heli; Olson, Janet E.; Orr, Nick; Perez, Jose I. A.; Pharoah, Paul D. P.; Ruddy, Kathryn J.; Saum, Kai-Uwe; Schoemaker, Minouk J.; Seynaeve, Caroline; Sironen, Reijo; Smit, Vincent T. H. B. M.; Swerdlow, Anthony J.; Tengstrom, Maria; Thomas, Abigail S.; Timmermans, A. Mieke; Tollenaar, Rob A. E. M.; Troester, Melissa A.; van Asperen, Christi J.; van Deurzen, Carolien H. M.; Van Leeuwen, Flora F.; Van'tVeer, Laura J. (2018)
    E-cadherin (CDH1) is a putative tumor suppressor gene implicated in breast carcinogenesis. Yet, whether risk factors or survival differ by E-cadherin tumor expression is unclear. We evaluated E-cadherin tumor immunohistochemistry expression using tissue microarrays of 5,933 female invasive breast cancers from 12 studies from the Breast Cancer Consortium. H-scores were calculated and case-case odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression. Survival analyses were performed using Cox regression models. All analyses were stratified by estrogen receptor (ER) status and histologic subtype. E-cadherin low cases (N = 1191, 20%) were more frequently of lobular histology, low grade, > 2 cm, and HER2-negative. Loss of E-cadherin expression (score <100) was associated with menopausal hormone use among ER-positive tumors (ever compared to never users, OR = 1.24, 95% CI = 0.97-1.59), which was stronger when we evaluated complete loss of E-cadherin (i.e. H-score = 0), OR = 1.57, 95% CI = 1.06-2.33. Breast cancer specific mortality was unrelated to E-cadherin expression in multivariable models. E-cadherin low expression is associated with lobular histology, tumor characteristics and menopausal hormone use, with no evidence of an association with breast cancer specific survival. These data support loss of E-cadherin expression as an important marker of tumor subtypes.
  • Veronese, N.; Sergi, G.; Stubbs, B.; Bourdel-Marchasson, I.; Tessier, D.; Sieber, C.; Strandberg, T.; Gillain, S.; Barbagallo, M.; Crepaldi, G.; Maggi, S.; Manzato, E.; EUGMS Special Interest Grp Diabet (2017)
    Background/aim: Deficiency of acetyl-L-carnitine (ALC) and L-carnitine (LC) appears to play a role in peripheral diabetic neuropathy, although the evidence in humans is still limited. We conducted a systematic review and meta-analysis investigating the effect of ALC on pain and electromyographic parameters in people with diabetic neuropathy. Methods: A literature search in major databases, without language restriction, was undertaken. Eligible studies were randomized controlled trials (RCTs) or pre-and post-test studies. The effect of ALC supplementation on pain perception and electromyographic parameters in patients with diabetic neuropathy was compared vs. a control group (RCTs). The effect of ALC/LC on electromyographic parameters were also calculated vs. baseline values. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were used for summarizing outcomes. Results: Six articles, with a total of 711 diabetic participants, were included. Three RCTs (340 treated with ALC vs. 203 placebo and 115 with methylcobalamine) showed that ALC reduces pain perception (SMD = -0.45; 95% CI: -0.86 to -0.04; P = 0.03; I-2 = 85%). Compared to controls, ALC supplementation improved nerve conduction velocity and amplitude response for ulnar nerve (both sensory and motor component). Compared to baseline values, ALC/LC supplementation improved nerve conduction velocity for all the sensory and motor nerves (except ulnar and peroneal) investigated and the amplitude of all nerves. The onset of adverse events was generally limited to minor side effects. Conclusion: ALC appears to be effective in reducing pain due to diabetic neuropathy compared to active or placebo controls and improving electromyographic parameters in these patients. (C) 2017 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
  • Costabile, Adele; Bergillos-Meca, Triana; Rasinkangas, Pia; Korpela, Katri; de Vos, Willem M.; Gibson, Glenn R. (2017)
    Background: The aging process leads to a potential decline in immune function and adversely affects the gut microbiota. To date, many in vitro and in vivo studies focused on the application of synbiotics (prebiotics combined with probiotics) as a promising dietary approach to affect gut microbiota composition and improved functioning of the immune system. However, studies using synbiotic preparations often have the limitation that it remains unclear whether any effect observed is a result of the prebiotic or probiotic or a synergistic effect of the combined supplement. Objectives: We investigated the effects of a probiotic Lactobacillus rhamnosus GG and pilus-deficient L. rhamnosus GG-PB12 combined with Promitor (TM) Soluble Corn Fiber (SCF, a candidate prebiotic) on fecal microbiota, metabolism, immunity, and blood lipids in healthy elderly persons. A prospective, double-blind, placebo controlled, randomized, single-centered, crossover study in 40 healthy elderly subjects (aged 60-80 years) was carried out. Volunteers were randomized to consume either probiotic and prebiotic as synbiotic, prebiotic or placebo (maltodextrin) during 3 weeks. Three-week washout periods separated all the treatments. We assessed effects upon blood lipids, glucose, cytokines, natural killer (NK) cell activity, phenotype, and intestinal microbiota composition. SCF decreased IL-6, which was not observed with the synbiotics. Results: Consumption of L. rhamnosus GG combined with SCF increased NK cell activity compared to baseline in females and the older group. In the fecal microbiota analyses, the strongest community shifts were due to L. rhamnosus GG combined with SCF and SCF treatments. L. rhamnosus GG combined with SCF and L. rhamnosus GG-PB12 combined with SCF significantly increased the genus Parabacteroides. L. rhamnosus GG combined with SCF and SCF increased concentrations of Ruminococcaceae Incertae Sedis. Oscillospira and Desulfovibrio slightly decreased in the L. rhamnosus GG combined with SCF group, whereas Desulfovibrio decreased also in the L. rhamnosus GG-PB12 combined with SCF group. L. rhamnosus GG combined with SCF reduced total cholesterol and LDL-cholesterol in volunteers with initially elevated concentrations. C-reactive protein significantly decreased during L. rhamnosus GG-PB12 combined with SCF intervention compared to baseline. Conclusion: In conclusion, the synbiotic combination of L. rhamnosus GG with SCF showed a tendency to promote innate immunity by increasing NK cell activity in elderly women and in 70 to 80-year-old volunteers and decreased TC and LDL-c in hyper-cholesterolemic patients. In addition, L. rhamnosus GG-PB12 combined with SCF demonstrated an increase in NK cell activity compared to SCF alone in older volunteers. We also found significant positive effects on the immune response, evidenced by a decrease of the pro-inflammatory cytokine IL-6. Therefore, dietary intervention with L. rhamnosus GG combined with SCF could be of importance in elderly as an attractive option for enhancement of both the microbial and immune systems.
  • Whelan, J. S.; Bielack, S. S.; Marina, N.; Smeland, S.; Jovic, G.; Hook, J. M.; Krailo, M.; Anninga, J.; Butterfass-Bahloul, T.; Bohling, T.; Calaminus, G.; Capra, M.; Deffenbaugh, C.; Dhooge, C.; Eriksson, M.; Flanagan, A. M.; Gelderblom, H.; Goorin, A.; Gorlick, R.; Gosheger, G.; Grimer, R. J.; Hall, K. S.; Helmke, K.; Hogendoorn, P. C. W.; Jundt, G.; Kager, L.; Kuehne, T.; Lau, C. C.; Letson, G. D.; Meyer, J.; Meyers, P. A.; Morris, C.; Mottl, H.; Nadel, H.; Nagarajan, R.; Randall, R. L.; Schomberg, P.; Schwarz, R.; Teot, L. A.; Sydes, M. R.; Bernstein, M.; EURAMOS Collaborators (2015)
  • Nast, A.; Smith, C.; Spuls, P. I.; Valle, G. Avila; Bata-Csörgö, Z.; Boonen, H.; De Jong, E.; Garcia-Doval, I.; Gisondi, P.; Kaur-Knudsen, D.; Mahil, S.; Mälkönen, T.; Maul, J. T.; Mburu, S.; Mrowietz, U.; Reich, K.; Remenyik, E.; Ronholt, K. M.; Sator, P. G.; Schmitt-Egenolf, M.; Sikora, M.; Stroemer, K.; Sundnes, O.; Trigos, D.; Van der Kraaij, G.; Yawalkar, N.; Dressler, C. (2020)
  • Malard, Florent; Labopin, Myriam; Cho, Christina; Blaise, Didier; Papadopoulos, Esperanza B.; Passweg, Jakob; O'Reilly, Richard; Forcade, Edouard; Maloy, Molly; Volin, Liisa; Castro-Malaspina, Hugo; Hicheri, Yosr; Jakubowski, Ann A.; Orvain, Corentin; Giralt, Sergio; Mohty, Mohamad; Nagler, Arnon; Perales, Miguel-Angel (2018)
    BackgroundGraft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT).MethodsWe evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell depletion using antithymocyte globulin (ATG) and ex vivo T cell depletion using a CD34-selected (CD34+) graft. A total of 525 adult patients (363 ATG, 162 CD34+) with intermediate or high-risk cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1) were included. Patients underwent myeloablative allo-HCT using matched related or unrelated donors.ResultsTwo-year overall survival estimate was 69.9% (95% CI, 58.5-69.4) in the ATG group and 67.6% (95% CI, 60.3-74.9) in the CD34+ group (p=0.31). The cumulative incidence of grade II-IV acute GVHD and chronic GVHD was higher in the ATG cohort [HR 2.0 (95% CI 1.1-3.7), p=0.02; HR 15.1 (95% CI 5.3-42.2), p
  • Global Burden Dis 2019; Abbafati, Cristiana; Abbas, Kaja M.; Abbasi, Mohammad; Kivimaki, Mika; Lallukka, Tea; Meretoja, Atte; Meretoja, Tuomo J.; Shiri, Rahman (2020)
    The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.
  • GBD 2019 Diss Injuries (2020)
    Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.
  • Salo, J.; Repo, J. P.; Roine, R. P.; Sintonen, H.; Tukiainen, E. J. (2019)
    Objectives: There is limited information of the health-related quality of life (HRQoL) after surgical treatment of chest wall tumors. This cross-sectional study aimed to assess long-term HRQoL after chest wall reconstruction following oncological resection. Methods: Seventy-eight patients having undergone chest wall tumor resection and reconstruction during 1997-2015 were invited to complete the 15D and QLQ-C30 HRQoL instruments. Results: Altogether, 55 patients (17 men and 38 women), with a mean (SD) age of 68 (14) years, completed the questionnaires (response rate 71%). Patients had been operated due to soft tissue sarcoma (n=16), advanced breast cancer (n=15), osteo- or chondrosarcoma (n=14), or other tumor (n=10). Median time after primary surgery was 66 (IQR 38, 141) months. The resection was full thickness in 29/55 cases and partial thickness in 26/55 cases. Chest wall reconstruction was required for 47/55 cases (85%). Reconstruction was performed using soft-tissue flap in eight cases, skeletal stabilizations with mesh or mesh-cement-mesh (sandwich method) in 15 cases, and skeletal stabilizations and soft-tissue flap in 24 cases. Patients' mean 15D score (0.878, SD 0.111) was comparable to that of the age- and gender-standardized general population (0.891, SD 0.041). Limitations in breathing and usual activities were noted. The QLQ-C30 cancer-specific HRQoL was 72 points (maximum 100). Scores in the QLQ-C30 Functional scales ranged from 78 (Physical) to 91 (Social). Conclusions: Long-term HRQoL in patients after chest wall reconstruction following oncological resection is fair and comparable to that of the general population. Limitations in breathing and usual activities can occur. (C) 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
  • Giles, Francis J.; Rea, Delphine; Rosti, Gianantonio; Cross, Nicholas C. P.; Luis Steegmann, Juan; Griskevicius, Laimonas; le Coutre, Philipp; Coriu, Daniel; Petrov, Ljubomir; Ossenkoppele, Gert J.; Mahon, Francois-Xavier; Saussele, Susanne; Hellmann, Andrzej; Koskenvesa, Perttu; Bruemmendorf, Tim H.; Gastl, Gunther; Castagnetti, Fausto; Vincenzi, Beatrice; Haenig, Jens; Hochhaus, Andreas (2017)
    Purpose Achievement of deep molecular response with a tyrosine kinase inhibitor in patients with chronic myeloid leukemia (CML) is required to attempt discontinuation of therapy in these patients. The current subanalysis from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study evaluated whether age has an impact on the achievement of deeper molecular responses or safety with frontline nilotinib in patients with CML. Methods ENEST1st is an open-label, multicenter, single-arm, prospective study of nilotinib 300 mg twice daily in patients with newly diagnosed CML in chronic phase. The patients were stratified into the following 4 groups based on age: young (18-39 years), middle age (40-59 years), elderly (60-74 years), and old (>= 75 years). The primary end point was the rate of molecular response 4 ([MR4] BCR-ABL1 Results Of the 1091 patients enrolled, 1089 were considered in the analysis, of whom, 23% (n = 243), 45% (n = 494), 27% (n = 300), and 5% (n = 52) were categorized as young, middle age, elderly, and old, respectively. At 18 months, the rates of MR4 were 33.9% (95% confidence interval [CI], 27.8-40.0%) in the young, 39.6% (95% CI, 35.3-44.0%) in the middle-aged, 40.5% (95% CI, 34.8-46.1%) in the elderly, and 35.4% (95% CI, 21.9-48.9%) in the old patients. Although the incidence of adverse events was slightly different, no new specific safety signals were observed across the 4 age groups. Conclusions This subanalysis of the ENEST1st study showed that age did not have a relevant impact on the deep molecular response rates associated with nilotinib therapy in newly diagnosed patients with CML and eventually on the eligibility of the patients to attempt treatment discontinuation.
  • Pollesello, P.; Parissis, J.; Kivikko, M.; Harjola, V. -P. (2016)
    Background: Levosimendan is an inodilator developed for treatment of acute heart failure and other cardiac conditions where the use of an inodilator is considered appropriate. Levosimendan has been studied in different therapeutic settings including acutely decompensated chronic heart failure, advanced heart failure, right ventricular failure, cardiogenic shock, septic shock, and cardiac and non-cardiac surgery. This variety of data has been re-analysed in 25 meta-analyses from 15 different international research groups, based on different rationales to select the studies included. Methods: We here review all previously published meta-analyses on levosimendan to determine any common denominators for its effects on patient mortality. In addition, we also perform a comparative meta-analysis of the six phase II and III randomized double-blind trials which were taken into consideration by the regulatory authorities for the purpose of introducing levosimendan into the market. Results: Irrespective of clinical setting or comparator, all meta-analyses consistently show benefits for levosimendan, with lower relative risk (or odds ratio) for patient mortality. In 3/25 of the meta-analyses these beneficial trends did not reach statistical significance, while in 22/25 significance was reached. The relative risk is consistent overall, and very similar to that obtained in our own meta-analysis that considered only the 'regulatory' studies. Conclusion: The existing meta-analyses, now based on a population of over 6000 patients, provide the general message of significant benefits for levosimendan in terms of patient mortality. The weight of evidence is now clearly in favour of usefulness/efficacy of levosimendan, with data from multiple randomized trials and meta-analyses. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.