Browsing by Subject "Meta-analysis"

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  • Mozhgani, Sayed-Hamidreza; Piran, Mehran; Zarei-Ghobadi, Mohadeseh; Jafari, Mohieddin; Jazayeri, Seyed-Mohammad; Mokhtari-Azad, Talat; Teymoori-Rad, Majid; Valizadeh, Narges; Farajifard, Hamid; Mirzaie, Mehdi; Khamseh, Azam; Rafatpanah, Houshang; Rezaee, Seyed-Abdolrahim; Norouzi, Mehdi (BioMed Central, 2019)
    Abstract Background Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. Results High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein–protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). Conclusions High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.
  • Mozhgani, Sayed-Hamidreza; Piran, Mehran; Zarei-Ghobadi, Mohadeseh; Jafari, Mohieddin; Jazayeri, Seyed-Mohammad; Mokhtari-Azad, Talat; Teymoori-Rad, Majid; Valizadeh, Narges; Farajifard, Hamid; Mirzaie, Mehdi; Khamseh, Azam; Rafatpanah, Houshang; Rezaee, Seyed-Abdolrahim; Norouzi, Mehdi (2019)
    Background Human T-lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive disease of the central nervous system that significantly affected spinal cord, nevertheless, the pathogenesis pathway and reliable biomarkers have not been well determined. This study aimed to employ high throughput meta-analysis to find major genes that are possibly involved in the pathogenesis of HAM/TSP. Results High-throughput statistical analyses identified 832, 49, and 22 differentially expressed genes for normal vs. ACs, normal vs. HAM/TSP, and ACs vs. HAM/TSP groups, respectively. The protein-protein interactions between DEGs were identified in STRING and further network analyses highlighted 24 and 6 hub genes for normal vs. HAM/TSP and ACs vs. HAM/TSP groups, respectively. Moreover, four biologically meaningful modules including 251 genes were identified for normal vs. ACs. Biological network analyses indicated the involvement of hub genes in many vital pathways like JAK-STAT signaling pathway, interferon, Interleukins, and immune pathways in the normal vs. HAM/TSP group and Metabolism of RNA, Viral mRNA Translation, Human T cell leukemia virus 1 infection, and Cell cycle in the normal vs. ACs group. Moreover, three major genes including STAT1, TAP1, and PSMB8 were identified by network analysis. Real-time PCR revealed the meaningful down-regulation of STAT1 in HAM/TSP samples than AC and normal samples (P = 0.01 and P = 0.02, respectively), up-regulation of PSMB8 in HAM/TSP samples than AC and normal samples (P = 0.04 and P = 0.01, respectively), and down-regulation of TAP1 in HAM/TSP samples than those in AC and normal samples (P = 0.008 and P = 0.02, respectively). No significant difference was found among three groups in terms of the percentage of T helper and cytotoxic T lymphocytes (P = 0.55 and P = 0.12). Conclusions High-throughput data integration disclosed novel hub genes involved in important pathways in virus infection and immune systems. The comprehensive studies are needed to improve our knowledge about the pathogenesis pathways and also biomarkers of complex diseases.
  • Hemilä, Harri (2017)
    Background: The relative scale has been used for decades in analysing binary data in epidemiology. In contrast, there has been a long tradition of carrying out meta-analyses of continuous outcomes on the absolute, original measurement, scale. The biological rationale for using the relative scale in the analysis of binary outcomes is that it adjusts for baseline variations; however, similar baseline variations can occur in continuous outcomes and relative effect scale may therefore be often useful also for continuous outcomes. The aim of this study was to determine whether the relative scale is more consistent with empirical data on treating the common cold than the absolute scale. Methods: Individual patient data was available for 2 randomized trials on zinc lozenges for the treatment of the common cold. Mossad (Ann Intern Med 125:81-8, 1996) found 4.0 days and 43% reduction, and Petrus (Curr Ther Res 59:595-607, 1998) found 1.77 days and 25% reduction, in the duration of colds. In both trials, variance in the placebo group was significantly greater than in the zinc lozenge group. The effect estimates were applied to the common cold distributions of the placebo groups, and the resulting distributions were compared with the actual zinc lozenge group distributions. Results: When the absolute effect estimates, 4.0 and 1.77 days, were applied to the placebo group common cold distributions, negative and zero (i.e., impossible) cold durations were predicted, and the high level variance remained. In contrast, when the relative effect estimates, 43 and 25%, were applied, impossible common cold durations were not predicted in the placebo groups, and the cold distributions became similar to those of the zinc lozenge groups. Conclusions: For some continuous outcomes, such as the duration of illness and the duration of hospital stay, the relative scale leads to a more informative statistical analysis and more effective communication of the study findings. The transformation of continuous data to the relative scale is simple with a spreadsheet program, after which the relative scale data can be analysed using standard meta-analysis software. The option for the analysis of relative effects of continuous outcomes directly from the original data should be implemented in standard meta-analysis programs.
  • Hemilä, Harri (BioMed Central, 2017)
    Abstract Background The relative scale has been used for decades in analysing binary data in epidemiology. In contrast, there has been a long tradition of carrying out meta-analyses of continuous outcomes on the absolute, original measurement, scale. The biological rationale for using the relative scale in the analysis of binary outcomes is that it adjusts for baseline variations; however, similar baseline variations can occur in continuous outcomes and relative effect scale may therefore be often useful also for continuous outcomes. The aim of this study was to determine whether the relative scale is more consistent with empirical data on treating the common cold than the absolute scale. Methods Individual patient data was available for 2 randomized trials on zinc lozenges for the treatment of the common cold. Mossad (Ann Intern Med 125:81–8, 1996) found 4.0 days and 43% reduction, and Petrus (Curr Ther Res 59:595–607, 1998) found 1.77 days and 25% reduction, in the duration of colds. In both trials, variance in the placebo group was significantly greater than in the zinc lozenge group. The effect estimates were applied to the common cold distributions of the placebo groups, and the resulting distributions were compared with the actual zinc lozenge group distributions. Results When the absolute effect estimates, 4.0 and 1.77 days, were applied to the placebo group common cold distributions, negative and zero (i.e., impossible) cold durations were predicted, and the high level variance remained. In contrast, when the relative effect estimates, 43 and 25%, were applied, impossible common cold durations were not predicted in the placebo groups, and the cold distributions became similar to those of the zinc lozenge groups. Conclusions For some continuous outcomes, such as the duration of illness and the duration of hospital stay, the relative scale leads to a more informative statistical analysis and more effective communication of the study findings. The transformation of continuous data to the relative scale is simple with a spreadsheet program, after which the relative scale data can be analysed using standard meta-analysis software. The option for the analysis of relative effects of continuous outcomes directly from the original data should be implemented in standard meta-analysis programs.
  • 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.
  • Calabro, Lorenzo; Bougouin, Wulfran; Cariou, Alain; De Fazio, Chiara; Skrifvars, Markus; Soreide, Eldar; Creteur, Jacques; Kirkegaard, Hans; Legriel, Stephane; Lascarrou, Jean-Baptiste; Megarbane, Bruno; Deye, Nicolas; Taccone, Fabio Silvio (2019)
    Background Although targeted temperature management (TTM) is recommended in comatose survivors after cardiac arrest (CA), the optimal method to deliver TTM remains unknown. We performed a meta-analysis to evaluate the effects of different TTM methods on survival and neurological outcome after adult CA. Methods We searched on the MEDLINE/PubMed database until 22 February 2019 for comparative studies that evaluated at least two different TTM methods in CA patients. Data were extracted independently by two authors. We used the Newcastle-Ottawa Scale and a modified Cochrane ROB tools for assessing the risk of bias of each study. The primary outcome was the occurrence of unfavorable neurological outcome (UO); secondary outcomes included overall mortality. Results Our search identified 6886 studies; 22 studies (n = 8027 patients) were included in the final analysis. When compared to surface cooling, core methods showed a lower probability of UO (OR 0.85 [95% CIs 0.75-0.96]; p = 0.008) but not mortality (OR 0.88 [95% CIs 0.62-1.25]; p = 0.21). No significant heterogeneity was observed among studies. However, these effects were observed in the analyses of non-RCTs. A significant lower probability of both UO and mortality were observed when invasive TTM methods were compared to non-invasive TTM methods and when temperature feedback devices (TFD) were compared to non-TFD methods. These results were significant particularly in non-RCTs. Conclusions Although existing literature is mostly based on retrospective or prospective studies, specific TTM methods (i.e., core, invasive, and with TFD) were associated with a lower probability of poor neurological outcome when compared to other methods in adult CA survivors (CRD42019111021).
  • Leopold, Valentine; Gayat, Etienne; Pirracchio, Romain; Spinar, Jindrich; Parenica, Jiri; Tarvasmäki, Tuukka; Lassus, Johan; Harjola, Veli-Pekka; Champion, Sebastien; Zannad, Faiez; Valente, Serafina; Urban, Philip; Chua, Horng-Ruey; Bellomo, Rinaldo; Popovic, Batric; Ouweneel, Dagmar M.; Henriques, Jose P. S.; Simonis, Gregor; Levy, Bruno; Kimmoun, Antoine; Gaudard, Philippe; Basir, Mir Babar; Markota, Andrej; Adler, Christoph; Reuter, Hannes; Mebazaa, Alexandre; Chouihed, Tahar (2018)
    Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients. We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality. Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17-76%) and short-term mortality rate was 49% (21-69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8-3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4-6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0-6.0]). In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death.
  • van den Berg, Stephanie M.; de Moor, Marleen H. M.; McGue, Matt; Pettersson, Erik; Terracciano, Antonio; Verweij, Karin J. H.; Amin, Najaf; Derringer, Jaime; Esko, Tonu; van Grootheest, Gerard; Hansell, Narelle K.; Huffman, Jennifer; Konte, Bettina; Lahti, Jari; Luciano, Michelle; Matteson, Lindsay K.; Viktorin, Alexander; Wouda, Jasper; Agrawal, Arpana; Allik, Jueri; Bierut, Laura; Broms, Ulla; Campbell, Harry; Smith, George Davey; Eriksson, Johan G.; Ferrucci, Luigi; Franke, Barbera; Fox, Jean-Paul; de Geus, Eco J. C.; Giegling, Ina; Gow, Alan J.; Grucza, Richard; Hartmann, Annette M.; Heath, Andrew C.; Heikkilä, Kauko; Iacono, William G.; Janzing, Joost; Jokela, Markus; Kiemeney, Lambertus; Lehtimaki, Terho; Madden, Pamela A. F.; Magnusson, Patrik K. E.; Northstone, Kate; Nutile, Teresa; Ouwens, Klaasjan G.; Palotie, Aarno; Pattie, Alison; Pesonen, Anu-Katriina; Polasek, Ozren; Pulkkinen, Lea; Pulkki-Raback, Laura; Raitakari, Olli T.; Realo, Anu; Rose, Richard J.; Ruggiero, Daniela; Seppala, Ilkka; Slutske, Wendy S.; Smyth, David C.; Sorice, Rossella; Starr, John M.; Sutin, Angelina R.; Tanaka, Toshiko; Verhagen, Josine; Vermeulen, Sita; Vuoksimaa, Eero; Widen, Elisabeth; Willemsen, Gonneke; Wright, Margaret J.; Zgaga, Lina; Rujescu, Dan; Metspalu, Andres; Wilson, James F.; Ciullo, Marina; Hayward, Caroline; Rudan, Igor; Deary, Ian J.; Räikkönen, Katri; Vasquez, Alejandro Arias; Costa, Paul T.; Keltikangas-Jarvinen, Liisa; van Duijn, Cornelia M.; Penninx, Brenda W. J. H.; Krueger, Robert F.; Evans, David M.; Kaprio, Jaakko; Pedersen, Nancy L.; Martin, Nicholas G.; Boomsma, Dorret I. (2014)
  • Knittle, Keegan Phillip; Nurmi, Johanna; Crutzen, Rik; Hankonen, Nelli Elisa; Beattie, Marguerite; Dombrowski, Stephan (2018)
    Motivation is a proximal determinant of behaviour, and increasing motivation is central to most health behaviour change interventions. This systematic review and meta-analysis sought to identify features of physical activity interventions associated with favourable changes in three prominent motivational constructs: intention, stage of change and autonomous motivation. A systematic literature search identified 89 intervention studies (k=200; N=19,212) which assessed changes in these motivational constructs for physical activity. Intervention descriptions were coded for potential moderators, including behaviour change techniques (BCTs), modes of delivery and theory use. Random effects comparative subgroup analyses identified 18 BCTs and 10 modes of delivery independently associated with changes in at least one motivational outcome (effect sizes ranged from d=0.12 to d=0.74). Interventions delivered face-to-face or in gym settings, or which included the BCTs behavioural goal setting', self-monitoring (behaviour)' or behavioural practice/rehearsal', or which combined self-monitoring (behaviour) with any other BCT derived from control theory, were all associated with beneficial changes in multiple motivational constructs (effect sizes ranged from d=0.12 to d=0.46). Meta-regression analyses indicated that increases in intention and stage of change, but not autonomous motivation, were significantly related to increases in physical activity. The intervention characteristics associated with changes in motivation seemed to form clusters related to behavioural experience and self-regulation, which have previously been linked to changes in physical activity behaviour. These BCTs and modes of delivery merit further systematic study, and can be used as a foundation for improving interventions targeting increases in motivation for physical activity.
  • Hodel, F.; Chong, A. Y.; Scepanovic, P.; Xu, Z. M.; Naret, O.; Thorball, C. W.; Rüeger, S.; Marques-Vidal, P.; Vollenweider, P.; Begemann, M.; Ehrenreich, H.; Brenner, N.; Bender, N.; Waterboer, T.; Mentzer, A. J.; Hill, A. V.S.; Hammer, C.; Fellay, J. (2021)
    Human polyomaviruses are widespread in humans and can cause severe disease in immunocompromised individuals. To identify human genetic determinants of the humoral immune response against polyomaviruses, we performed genome-wide association studies and meta-analyses of qualitative and quantitative immunoglobulin G responses against BK polyomavirus (BKPyV), JC polyomavirus (JCPyV), Merkel cellpolyomavirus (MCPyV), WU polyomavirus (WUPyV), and human polyomavirus 6 (HPyV6) in 15,660 individuals of European ancestry from three independent studies. We observed significant associations for all tested viruses: JCPyV, HPyV6, and MCPyV associated with human leukocyte antigen class II variation, BKPyV and JCPyV with variants in FUT2, responsible for secretor status, MCPyV with variants in STING1, involved in interferon induction, and WUPyV with a functional variant in MUC1, previously associated with risk for gastric cancer. These results provide insights into the genetic control of a family of very prevalent human viruses, highlighting genes and pathways that play a modulating role in human humoral immunity.
  • Bobbio, Emanuele; Lingbrant, Marie; Nwaru, Bright; Hessman, Eva; Lehtonen, Jukka; Karason, Kristjan; Bollano, Entela (2020)
    Heart transplantation (HTx) for patients with "giant cell myocarditis" (GCM) or "cardiac sarcoidosis" (CS) is still controversial. However, no single center has accumulated enough experience to investigate post-HTx outcome. The primary aim of this systematic review is to identify, appraise, and synthesize existing literature investigating whether patients who have undergone HTx because of GCM or CS have worse outcomes as compared with patients transplanted because of other etiologies. A systematic and comprehensive search will be performed using PubMed, Scopus, Web of Science, EMBASE, and Google Scholar, for studies published up to December 2019. Observational and interventional population-based studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle-Ottawa scale, while the interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesized; in addition, we will perform a meta-analysis to pool estimates from studies considered to be homogenous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. To our knowledge, this will be the first synthesis of outcomes, including survival, acute cellular rejection, and disease recurrence, in patients with either GCM or CS treated with HTx. Reviewing the suitability of HTx in this population and highlighting areas for further research will benefit both patients and healthcare providers. Trial registration: CRD42019140574.
  • Garcia-Larsen, Vanessa; Arthur, Rhonda; Potts, James F.; Howarth, Peter H.; Ahlström, Matti; Haahtela, Tari Markku Kallevi; Loureiro, Carlos; Bom, Ana Todo; Brozek, Grzegorz; Makowska, Joanna; Kowalski, Marek L.; Thilsing, Trine; Keil, Thomas; Matricardi, Paolo M.; Toren, Kjell; van Zele, Thibaut; Bachert, Claus; Rymarczyk, Barbara; Janson, Christer; Forsberg, Bertil; Nizankowska-Mogilnicka, Ewa; Burney, Peter G. J. (2017)
    Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. Objective: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. Methods: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA(2)LEN) screening survey, in which 55,000 adults aged 15-75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA(2)LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. Results: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score >= 1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (beta-coefficient -2.34;95% confidence interval [CI] -4.09,-0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted beta-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. Conclusion and clinical relevance: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.
  • Garcia-Larsen, Vanessa; Arthur, Rhonda; Potts, James F; Howarth, Peter H; Ahlström, Matti; Haahtela, Tari; Loureiro, Carlos; Bom, Ana T; Brożek, Grzegorz; Makowska, Joanna; Kowalski, Marek L; Thilsing, Trine; Keil, Thomas; Matricardi, Paolo M; Torén, Kjell; van Zele, Thibaut; Bachert, Claus; Rymarczyk, Barbara; Janson, Christer; Forsberg, Bertil; Niżankowska-Mogilnicka, Ewa; Burney, Peter G J (BioMed Central, 2017)
    Abstract Background Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. Objective We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. Methods A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA2LEN) screening survey, in which 55,000 adults aged 15–75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA2LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. Results A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8% reported having at least 1 asthma symptom (asthma score ≥1), whilst 19.5% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (β-coefficient −2.34; 95% confidence interval [CI] −4.09, −0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted β-coefficient 0.23; 95% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. Conclusion and clinical relevance There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.
  • 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.
  • Virtanen, Marianna; Kivimäki, Mika (2018)
    To summarize the evidence on the relationship between long working hours and cardiovascular disease, such as coronary heart disease and stroke. Large-scale meta-analyses with published and individual participant observational data on more than 740,000 men and women free of cardiovascular disease report a link between long working hours (>= 55 h a week) and the onset of cardiovascular events. Our meta-analytic update of summary evidence suggests a 1.12-fold (95% CI 1.03-1.21) increased risk associated with coronary heart disease and a 1.21-fold (95% CI 1.01-1.45) increased risk of stroke, although the evidence is somewhat inconsistent and the possibility of residual confounding and bias cannot be ruled out. Few studies have examined the mechanisms which may be stress-related, behavioral, or biological. The recent pooled analyses suggest that increased cardiac electric instability and hypercoagulability might play a role. The evidence that long working hours are a risk factor for cardiovascular disease is accumulating and suggests a small risk. Studies on the effects of long working hours in high-risk populations and those with pre-existing cardiovascular disease, mechanistic research, and intervention studies are needed to advance this research field.
  • Karavitakis, Markos; Kyriazis, Iason; Omar, Muhammad Imran; Gravas, Stavros; Cornu, Jean-Nicolas; Drake, Marcus J.; Gacci, Mauro; Gratzke, Christian; Herrmann, Thomas R. W.; Madersbacher, Stephan; Rieken, Malte; Speakman, Mark J.; Tikkinen, Kari A. O.; Yuan, Yuhong; Mamoulakis, Charalampos (2019)
    Context: Practice patterns for the management of urinary retention (UR) secondary to benign prostatic obstruction (BPO; UR/BPO) vary widely and remain unstandardized. Objective: To review the evidence for managing patients with UR/BPO with pharmacological and nonpharmacological treatments included in the European Association of Urology guidelines on non-neurogenic male lower urinary tract symptoms. Evidence acquisition: Search was conducted up to April 22, 2018, using CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. This systematic review included randomized controlled trials (RCTs) and prospective comparative studies. Methods as detailed in the Cochrane handbook were followed. Certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Evidence synthesis: Literature search identified 2074 citations. Twenty-one studies were included (qualitative synthesis). The evidence for managing patients with UR/BPO with pharmacological or nonpharmacological treatments is limited. CoE for most outcomes was low/very low. Only alpha 1-blockers (alfuzosin and tamsulosin) have been evaluated in more than one RCT. Pooled results indicated that a1-blockers provided significantly higher rates of successful trial without catheter compared with placebo [alfuzosin: 322/540 (60%) vs 156/400 (39%) (odds ratio {OR} 2.28, 95% confidence interval {CI} 1.55 to 3.36; participants = 940; studies = 7; I-2 = 41%; low CoE); tamsulosin: 75/158 (47%) vs 40/139 (29%) (OR 2.40, 95% CI 1.29 to 4.45; participants = 297; studies = 3; I-2 = 30%; low CoE)] with rare adverse events. Similar rates were achieved with tamsulosin or alfuzosin [51/87 (59%) vs 45/84 (54%) (OR 1.28, 95% CI 0.68 to 2.41;participants = 171; studies = 2; I-2 = 0%; very low CoE)]. Nonpharmacological treatments have been evaluated in RCTs/prospective comparative studies only sporadically. Conclusions: There is some evidence that usage of alpha 1-blockers (alfuzosin and tamsulosin) may improve resolution of UR/BPO. As most nonpharmacological treatments have not been evaluated in patients with UR/BPO, the evidence is inconclusive about their benefits and harms. Patient summary: There is some evidence that alfuzosin and tamsulosin may increase the rates of successful trial without catheter, but little or no evidence on various nonpharmacological treatment options for managing patients with urinary retention secondary to benign prostatic obstruction. (c) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
  • Hemilä, Harri; Friedrich, Jan O (BioMed Central, 2019)
    Abstract Background The relative scale adjusts for baseline variability and therefore may lead to findings that can be generalized more widely. It is routinely used for the analysis of binary outcomes but only rarely for continuous outcomes. Our objective was to compare relative vs absolute scale pooled outcomes using data from a recently published Cochrane systematic review that reported only absolute effects of inhaled β2-agonists on exercise-induced decline in forced-expiratory volumes in 1 s (FEV1). Methods From the Cochrane review, we selected placebo-controlled cross-over studies that reported individual participant data (IPD). Reversal in FEV1 decline after exercise was modeled as a mean uniform percentage point (pp) change (absolute effect) or average percent change (relative effect) using either intercept-only or slope-only, respectively, linear mixed-effect models. We also calculated the pooled relative effect estimates using standard random-effects, inverse-variance-weighting meta-analysis using study-level mean effects. Results Fourteen studies with 187 participants were identified for the IPD analysis. On the absolute scale, β2-agonists decreased the exercise-induced FEV1 decline by 28 pp., and on the relative scale, they decreased the FEV1 decline by 90%. The fit of the statistical model was significantly better with the relative 90% estimate compared with the absolute 28 pp. estimate. Furthermore, the median residuals (5.8 vs. 10.8 pp) were substantially smaller in the relative effect model than in the absolute effect model. Using standard study-level meta-analysis of the same 14 studies, β2-agonists reduced exercise-induced FEV1 decline on the relative scale by a similar amount: 83% or 90%, depending on the method of calculating the relative effect. Conclusions Compared with the absolute scale, the relative scale captures more effectively the variation in the effects of β2-agonists on exercise-induced FEV1-declines. The absolute scale has been used in the analysis of FEV1 changes and may have led to sub-optimal statistical analysis in some cases. The choice between the absolute and relative scale should be determined based on biological reasoning and empirical testing to identify the scale that leads to lower heterogeneity.
  • Coleman, Ruth L.; Scott, Charles A. B.; Lang, Zhihui; Bethel, M. Angelyn; Tuomilehto, Jaakko; Holman, Rury R. (2019)
    Background Alpha-glucosidase inhibitors (AGIs) have been shown to reduce incident type 2 diabetes but their impact on cardiovascular (CV) disease remains controversial. We sought to identify the overall impact of AGIs with respect to incident type 2 diabetes in individuals with impaired glucose tolerance (IGT), and CV outcomes in those with IGT or type 2 diabetes. Methods We used PubMed and SCOPUS to identify randomized controlled trials reporting the incidence of type 2 diabetes and/or CV outcomes that had compared AGIs with placebo in populations with IGT or type 2 diabetes, with or without established CV disease. Eligible studies were required to have >= 500 participants and/or >= 100 endpoints of interest. Meta-analyses of available trial data were performed using random effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and CV outcomes. Results Of ten trials identified, three met our inclusion criteria for incident type 2 diabetes and four were eligible for CV outcomes. The overall HR (95% CI) comparing AGI with placebo for incident type 2 diabetes was 0.77 (0.67-0.88), p <0.0001, and for CV outcomes was 0.98 (0.89-1.10), p = 0.85. There was little to no heterogeneity between studies, with I-2 values of 0.03% (p = 0.43) and 0% (p = 0.79) for the two outcomes respectively. Conclusions Allocation of people with IGT to an AGI significantly reduced their risk of incident type 2 diabetes by 23%, whereas in those with IGT or type 2 diabetes the impact on CV outcomes was neutral.
  • Coleman, Ruth L; Scott, Charles A B; Lang, Zhihui; Bethel, M. A; Tuomilehto, Jaakko; Holman, Rury R (BioMed Central, 2019)
    Abstract Background Alpha-glucosidase inhibitors (AGIs) have been shown to reduce incident type 2 diabetes but their impact on cardiovascular (CV) disease remains controversial. We sought to identify the overall impact of AGIs with respect to incident type 2 diabetes in individuals with impaired glucose tolerance (IGT), and CV outcomes in those with IGT or type 2 diabetes. Methods We used PubMed and SCOPUS to identify randomized controlled trials reporting the incidence of type 2 diabetes and/or CV outcomes that had compared AGIs with placebo in populations with IGT or type 2 diabetes, with or without established CV disease. Eligible studies were required to have ≥ 500 participants and/or ≥ 100 endpoints of interest. Meta-analyses of available trial data were performed using random effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and CV outcomes. Results Of ten trials identified, three met our inclusion criteria for incident type 2 diabetes and four were eligible for CV outcomes. The overall HR (95% CI) comparing AGI with placebo for incident type 2 diabetes was 0.77 (0.67–0.88), p < 0.0001, and for CV outcomes was 0.98 (0.89–1.10), p = 0.85. There was little to no heterogeneity between studies, with I2 values of 0.03% (p = 0.43) and 0% (p = 0.79) for the two outcomes respectively. Conclusions Allocation of people with IGT to an AGI significantly reduced their risk of incident type 2 diabetes by 23%, whereas in those with IGT or type 2 diabetes the impact on CV outcomes was neutral.
  • Int Liaison Comm Resuscitation; Buick, Jason E.; Wallner, Clare; Aickin, Richard; Meaney, Peter A.; de Caen, Allan; Maconochie, Ian; Skrifvars, Markus B.; Welsford, Michelle (2019)
    Introduction: The International Liaison Committee on Resuscitation prioritized the need to update the review on the use of targeted temperature management (TTM) in paediatric post cardiac arrest care. In this meta-analysis, the effectiveness of TTM at 32-36 degrees C was compared with no target or a different target for comatose children who achieve a return of sustained circulation after cardiac arrest. Methods: Electronic databases were searched from inception to December 13, 2018. Randomized controlled trials and non-randomized studies with a comparator group that evaluated TTM in children were included. Pairs of independent reviewers extracted the demographic and outcome data, appraised risk of bias, and assessed GRADE certainty of effects. A random effects meta-analysis was undertaken where possible. Results: Twelve studies involving 2060 patients were included. Two randomized controlled trials provided the evidence that TTM at 32-34 degrees C compared with a target at 36-37.5 degrees C did not statistically improve long-term good neurobehavioural survival (risk ratio: 1.15; 95% CI: 0.69-1.93), long-term survival (RR: 1.14; 95% CI: 0.93-1.39), or short-term survival (risk ratio: 1.14; 95% CI: 0.96-1.36). TTM at 32-34 degrees C did not show statistically increased risks of infection, recurrent cardiac arrest, serious bleeding, or arrhythmias. A novel analysis suggests that another small RCT might provide enough evidence to show benefit for TTM in out-of-hospital cardiac arrest. Conclusion: There is currently inconclusive evidence to either support or refute the use of TTM at 32-34 degrees C for comatose children who achieve return of sustained circulation after cardiac arrest. Future trials should focus on children with out-of-hospital cardiac arrest.