Browsing by Subject "major clinical study"

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  • Komulainen, K; Pulkki-Raback, L; Jokela, M; Lyytikäinen, LP; Pitkänen, N; Laitinen, T; Hintsanen, M; Elovainio, M; Hintsa, T; Jula, A (2018)
    Objectives:The life-course development of body mass index (BMI) may be driven by interactions between genes and obesity-inducing social environments. We examined whether lower parental or own education accentuates the genetic risk for higher BMI over the life course, and whether diet and physical activity account for the educational differences in genetic associations with BMI.Subjects/Methods:The study comprised 2441 participants (1319 women, 3-18 years at baseline) from the prospective, population-based Cardiovascular Risk in Young Finns Study. BMI (kg/m 2) trajectories were calculated from 18 to 49 years, using data from six time points spanning 31 years. A polygenic risk score for BMI was calculated as a weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was assessed via self-reports, measured prospectively from participants in adulthood and from parents when participants were children. Diet and physical activity were self-reported in adulthood.Results:Mean BMI increased from 22.6 to 26.6 kg/m 2 during the follow-up. In growth curve analyses, the genetic risk score was associated with faster BMI increase over time (b=0.02, (95% CI, 0.01-0.02, P
  • ALBINO Study Group; Maiwald, C.A.; Annink, K.V.; Rüdiger, M.; Benders, M.J.N.L.; Van Bel, F.; Allegaert, K.; Naulaers, G.; Bassler, D.; Klebermaß-Schrehof, K.; Vento, M.; Guimarães, H.; Stiris, T.; Cattarossi, L.; Metsäranta, M.; Vanhatalo, S.; Mazela, J.; Metsvaht, T.; Jacobs, Y. (2019)
    Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017. © 2019 The Author(s).
  • Kuchenbaecker, K.B.; McGuffog, L.; Barrowdale, D.; Lee, Andrew; Soucy, P.; Dennis, J.; Domchek, S.M.; Robson, M.; Spurdle, A.B.; Ramus, S.J.; Mavaddat, N.; Terry, M.B.; Neuhausen, S.L.; Schmutzler, R.K.; Simard, J.; Pharoah, P.D.P.; Offit, K.; Couch, F.J.; Chenevix-Trench, G.; Easton, D.F.; Antoniou, A.C.; Healey, S.; Lush, M.; Hamann, U.; Southey, M.; John, E.M.; Chung, W.K.; Daly, M. B.; Buys, S.S.; Goldgar, D.E.; Dorfling, C.M.; van Rensburg, E.J.; Ding, Y.C.; Ejlertsen, B.; Gerdes, A.-M.; Hansen, T.V.O.; Slager, S.; Hallberg, E.; Benitez, J.; Osorio, A.; Cohen, N.; Lawler, W.; Weitzel, J.N.; Peterlongo, P.; Pensotti, V.; Dolcetti, R.; Barile, M.; Aittomäki, K.; Nevanlinna, H.; Rantala, J. (2017)
    Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 × 10-53). InBRCA2 carriers, the strongest association with BC risk was seen for the overall BCPRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 × 10-20). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management. © The Author 2017.
  • eQTLGen Consortium (2018)
    Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r b ). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples (r b = 0.70 for cis-eQTLs and r ^ b = 0.78 for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes. © 2018 The Author(s).
  • Vink, P.; Torrell, J.M.R.; Fructuoso, A.S.; Kim, Sung-Joo; Kim, Sang-Il; Zaltzman, J.; Ortiz, F.; Plana, J.M.C.; Rodriguez, A.M.F.; Rodrigo, H.R.; Marti, M.C.; Perez, R.; Roncero, F.M.G.; Kumar, D.; Chiang, Y.-J.; Doucette, K.; Pipeleers, L.; Morales, M.L.A.; Rodriguez-Ferrero, M.L.; Secchi, Antonio; McNeil, S.A.; Campora, L.; Di Paolo, E.; El Idrissi, M.; López-Fauqued, M.; Salaun, B.; Heineman, T.C.; Oostvogels, L. (2020)
    Background. The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. Methods. In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1-2 months (M) apart 4-18M posttransplant. Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2. Results. Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post-dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups. Conclusions. RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose. © The Author(s) 2019.
  • Taipale, Kristian; Tähtinen, Siri; Havunen, Riikka; Koski, Anniina; Liikanen, Ilkka; Pakarinen, Päivi; Koivisto-Korander, Riitta; Kankainen, Matti; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli (2018)
    After the landmark approval of T-VEC, oncolytic viruses are finding their way to the clinics. However, response rates have still room for improvement, and unfortunately there are currently no available markers to predict responses for oncolytic immunotherapy. Interleukin 8 (IL-8) production is upregulated in many cancers and it also connects to several pathways that have been shown to impair the efficacy of adenoviral immunotherapy. We studied the role of IL-8 in 103 cancer patients treated with oncolytic adenoviruses. We found high baseline serum IL-8 concentration to be independently associated with poor prognosis (p <0.001). Further, normal baseline IL-8 was associated with improved prognostic potential of calculation of the neutrophil-to-lymphocyte ratio (p <0.001). Interestingly, a decrease in IL-8 concentration after treatment with oncolytic adenovirus predicted better overall survival (p <0.001) and higher response rate, although this difference was not significant (p=0.066). We studied the combination of adenovirus and IL-8 neutralizing antibody ex vivo in single cell suspensions and in co-cultures of tumor-associated CD15+ neutrophils and CD3+ tumor-infiltrating lymphocytes derived from fresh patient tumor samples. These results indicate a role for IL-8 as a biomarker in oncolytic virotherapy, but additionally provide a rationale for targeting IL-8 to improve treatment efficacy. In conclusion, curtailing the activity of IL-8 systemically or locally in the tumor microenvironment could improve anti-tumor immune responses resulting in enhanced efficacy of adenoviral immunotherapy of cancer. © Taipale et al.
  • Melén, Krister; Jalkanen, Pinja; Kukkonen, Jyrki P.; Partinen, Markku; Nohynek, Hanna; Vuorela, Arja; Vaarala, O.; Freitag, Tobias L.; Meri, Seppo; Julkunen, Ilkka (2020)
    Narcolepsy type 1, likely an immune-mediated disease, is characterized by excessive daytime sleepiness and cataplexy. The disease is strongly associated with human leukocyte antigen (HLA) DQB1∗06:02. A significant increase in the incidence of childhood and adolescent narcolepsy was observed after a vaccination campaign with AS03-adjuvanted Pandemrix influenza vaccine in Nordic and several other countries in 2010 and 2011. Previously, it has been suggested that a surface-exposed region of influenza A nucleoprotein, a structural component of the Pandemrix vaccine, shares amino acid residues with the first extracellular domain of the human OX2 orexin/hypocretin receptor eliciting the development of autoantibodies. Here, we analyzed, whether H1N1pdm09 infection or Pandemrix vaccination contributed to the development of autoantibodies to the orexin precursor protein or the OX1 or OX2 receptors. The analysis was based on the presence or absence of autoantibody responses against analyzed proteins. Entire OX1 and OX2 receptors or just their extracellular N-termini were transiently expressed in HuH7 cells to determine specific antibody responses in human sera. Based on our immunofluorescence analysis, none of the 56 Pandemrix-vaccinated narcoleptic patients, 28 patients who suffered from a laboratory-confirmed H1N1pdm09 infection or 19 Pandemrix-vaccinated controls showed specific autoantibody responses to prepro-orexin, orexin receptors or the isolated extracellular N-termini of orexin receptors. We also did not find any evidence for cell-mediated immunity against the N-terminal epitopes of OX2. Our findings do not support the hypothesis that the surface-exposed region of the influenza nucleoprotein A would elicit the development of an immune response against orexin receptors. © 2020 The Authors
  • Yu, Hongyao; Frank, Christopher; Hemminki, A.; Sundquist, Kristiina; Hemminki, K. (2017)
    Familial risks of lung cancer are well-established, but whether lung cancer clusters with other discordant cancers is less certain, particularly beyond smoking-related sites, which may provide evidence on genetic contributions to lung cancer aetiology. We used a novel approach to search for familial associations in the Swedish Family-Cancer Database. This involved assessment of familial relative risk for cancer X in families with increasing numbers of lung cancer patients and, conversely, relative risks for lung cancer in families with increasing numbers of patients with cancers X. However, we lacked information on smoking. The total number of lung cancers in the database was 125 563. We applied stringent statistical criteria and found that seven discordant cancers were associated with lung cancer among family members, and six of these were known to be connected with smoking: oesophageal, upper aerodigestive tract, liver, cervical, kidney and urinary bladder cancers. A further novel finding was that cancer of unknown primary also associated with lung cancer. We also factored in histological evidence and found that anal and connective tissue cancers could be associated with lung cancer for reasons other than smoking. For endometrial and prostate cancers, suggestive negative associations with lung cancer were found. Although we lacked information on smoking it is prudent to conclude that practically all observed discordant associations of lung cancer were with cancers for which smoking is a risk factor. © ERS 2017.
  • Hänninen-Khoda, L.; Koljonen, V.; Ylä-Kotola, T. (2018)
    Late cancellations of scheduled operations cause direct and indirect costs for a hospital and economic and emotional stress for the patient. Previously, late cancellation rates for scheduled operations in plastic surgery have been shown to be attributable to patient-related causes in the majority of cases. In this retrospective study, we sought to examine specifically the patient-related reasons for the late cancellations in a plastic surgery operating theatre at Helsinki University Hospital in Finland from 2013 to 2014. We calculated latency between the date of decision for surgery and the scheduled operation day. In cases where the surgery was rescheduled and performed before 31 December 2015, the rescheduled waiting time latency was calculated. We aimed to improve our knowledge of the causes of late cancellations to further optimise the operating theatre efficiency and propose a strategic algorithm to avoid late cancellations During the study period, 327 (5.5%) of all the scheduled operations were recorded as late cancellations. Of these, 45.3% were because of patient-related issues. Acute infection, change in medical condition not noticed before and operation no longer necessary were by far the most common causes of cancellation, comprising 63.5%. Sixty-six per cent of patient-related cancelled operations were performed later, especially when the specific reason was patient's acute illness. Root-cause analysis shows that most of the underlying reasons for the cancellations can be attributed to a failure in communication. The majority of these cancellations were considered to be preventable, thus emphasising the importance of communication and skilful multi-professional planning of the operating theatre list. © 2018 The Author(s)
  • Uusitalo, Karoliina; Haataja, Leena; Nyman, Anna; Ripatti, Liisi; Huhtala, Mira; Rautava, Päivi; Lehtonen, Liisa; Parkkola, Riitta; Lahti, Katri; Koivisto, Mari; Setänen, Sirkku (2020)
    Objective To evaluate the rate of developmental coordination disorder (DCD) and its correlation to cognition and self-experienced health-related quality of life (HRQoL) in children born very preterm. Design Prospective follow-up study. Setting Regional population of children born very preterm in Turku University Hospital, Finland, in 2001-2006. Patients A total of 170 children born very preterm were followed up until 11 years of age. Main outcome measures Motor and cognitive outcomes were evaluated using the Movement Assessment Battery for Children -Second Edition (Movement ABC-2) and the Wechsler Intelligence Scale for Children -Fourth Edition, respectively, and HRQoL using the 17-Dimensional Illustrated Questionnaire (17D). The Touwen neurological examination was performed to exclude other neurological conditions affecting the motor outcome. Results Eighteen children born very preterm (17 boys) (11.3%) had DCD, defined as Movement ABC-2 total test score ≤5th percentile. A positive correlation between motor and cognitive outcome (r=0.22, p=0.006) was found. Children born very preterm with DCD had lower cognitive scores than those without DCD (Full-Scale IQ mean 76.8 vs 91.6, p=0.001). Moreover, children born very preterm with DCD reported lower HRQoL than children born very preterm without motor impairment (17D mean 0.93 vs 0.96, p=0.03). However, HRQoL was higher in this group of children born very preterm compared with population-based normative test results (p
  • Smeekes, A.; Jetten, J.; Verkuyten, M.; Wohl, M.J.A.; Jasinskaja-Lahti, I.; Ariyanto, A.; Autin, F.; Ayub, N.; Badea, C.; Besta, T.; Butera, F.; Costa-Lopes, R.; Cui, L.; Fantini, C.; Finchilescu, G.; Gaertner, L.; Gollwitzer, M.; Gómez, Á.; González, R.; Hong, Y.Y.; Jensen, D.Hø.; Karasawa, M.; Kessler, T.; Klein, O.; Lima, M.; Renvik, T.A.; Megevand, L.; Morton, T.; Paladino, P.; Polya, T.; Ruza, A.; Shahrazad, W.; Sharma, Sushama; Teymoori, A.; Torres, A.R.; Van Der Bles, A.M. (2018)
    Collective nostalgia for the good old days of the country thrives across the world. However, little is known about the social psychological dynamics of this collective emotion across cultures. We predicted that collective nostalgia is triggered by collective angst as it helps people to restore a sense of in-group continuity via stronger in-group belonging and out-group rejection (in the form of opposition to immigrants). Based on a sample (N = 5,956) of individuals across 27 countries, the general pattern of results revealed that collective angst predicts collective nostalgia, which subsequently relates to stronger feelings of in-group continuity via in-group belonging (but not via out-group rejection). Collective nostalgia generally predicted opposition to immigrants, but this was subsequently not related to in-group continuity. © 2018 Hogrefe Publishing.
  • Kraus, W.E.; Yates, T.; Tuomilehto, J.; Sun, J.-L.; Thomas, L.; Mcmurray, J.J.V.; Bethel, M.A.; Holman, R.R. (2018)
    Objective: Physical activity is related to clinical outcomes, even after adjusting for body mass, but is rarely assessed in randomized clinical trials. Research design and methods: We conducted an observational analysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial, in which a total of 9306 people from 40 countries with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors were randomized to receive nateglinide or placebo, in a 2-by-2 factorial design with valsartan or placebo. All were asked to also participate in a detailed lifestyle modification programme and followed-up for a median of 6.4 years with progression to diabetes as a co-primary end point. Seven-day ambulatory activity was assessed at baseline using research-grade pedometers. We assessed whether the baseline amount of physical activity was related to subsequent development of diabetes in individuals with impaired glucose tolerance. Results: Pedometer data were obtained on 7118 participants and 35.0% developed diabetes. In an unadjusted analysis each 2000-step increment in the average number of daily steps, up to 10 000, was associated with a 5.5% lower risk of progression to diabetes (HR 0.95, 95%CI 0.92 to 0.97), with >6% relative risk reduction after adjustment. Conclusions: Physical activity should be measured objectively in pharmacologic trials as it is a significant but underappreciated contributor to diabetes outcomes. It should be a regular part of clinical practice as well. © 2018 Author(s) (or their employer(s).
  • Fizazi, Karim; Massard, Christophe; Bono, P.; Kataja, Vesa; James, Nicholas; Tammela, T.L.; Joensuu, H.; Aspegren, John; Mustonen, M. (2017)
    Background: Patients with castration-resistant prostate cancer (CRPC) had extended responses to the androgen receptor antagonist ODM-201, in phase 1/2 studies. Objective: To evaluate the safety and antitumour activity of prolonged ODM-201 treatment in patients with CRPC. Design, setting, and participants: The ARADES trial was a multicentre phase 1 (dose escalation) and phase 2 (dose expansion) trial; 134 patients with CRPC were stratified by previous chemotherapy to receive ODM-201. This paper reports extended follow-up in CYP17 inhibitor (CYP17i)-naïve patients. Intervention: Patients (n = 77) received oral ODM-201 twice daily at daily doses of 200–1800 mg. Outcome measurements and statistical analysis: Safety, measured as the occurrence of adverse events (AEs), prostate-specific antigen (PSA), and radiographic progression. Results and limitations: The safety profile of extended ODM-201 treatment (median treatment duration 8.2 mo, 95% confidence interval [CI] 5.6–11.0) was consistent with that reported at the time of the original data cutoff in the main ARADES trial, with no unexpected safety concerns over time. The majority of AEs (61.1%) were mild (grade 1); the most common AE was fatigue/asthenia (35.1% of patients), with no clear relationship to ODM-201. Median time to PSA progression was 25.2 mo (95% CI 11.3–25.2) for chemotherapy-naïve men and not reached (NR; 95% CI 5.5–NR) for chemotherapy-pretreated patients; a trend for improved antitumour response was observed for chemotherapy-naïve patients. The median time to radiographic progression was longer for chemotherapy-naïve (14.0 mo, 95% CI 8.1–33.3) than for chemotherapy-pretreated (7.2 mo, 95% CI 2.7–11.0) patients. Conclusions: Prolonged exposure to ODM-201 was well tolerated, with no additional safety concerns; disease suppression was sustained, especially in chemotherapy-naïve patients. These data support further development of ODM-201 in men with CYP17i-naïve CRPC. Patient summary: Extended ODM-201 therapy was well tolerated, with beneficial antitumour activity in men with advanced prostate cancer, indicating that ODM-201 may represent a new active treatment for men with CRPC. This extension trial is registered at ClinicalTrials.gov (www.clinicaltrials.gov) under identification number NCT01429064. Extended ODM-201 therapy showed encouraging antitumour activity in both chemotherapy-naïve and chemotherapy-treated men with metastatic castration-resistant prostate cancer (CRPC). Continued treatment with ODM-201 was well tolerated, with no unexpected safety concerns, and may represent a new, effective treatment option for men with CRPC. © 2017 European Association of Urology
  • Pihlajamäki, Minna; Uitti, J.; Arola, H.; Ollikainen, J.; Korhonen, M.; Nummi, T.; Taimela, S. (2019)
    Objectives To study whether self-reported health problems predict sickness absence (SA) from work in employees from different industries. Methods The results of a health risk appraisal (HRA) were combined with archival data of SA of 21 608 employees (59% female, 56% clerical). Exposure variables were self-reported health problems, labelled as ' work disability (WD) risk factors' in the HRA, presence of problems with occupational well-being and obesity. Age, socioeconomic grading and the number of SA days 12 months before the survey were treated as confounders. The outcome measure was accumulated SA days during 12-month follow-up. Data were analysed separately for males and females. A Hurdle model with negative binomial response was used to analyse zero-inflated count data of SA. Results The HRA results predicted the number of accumulated SA days during the 12-month follow-up, regardless of occupational group and gender. The ratio of means of SA days varied between 2.7 and 4.0 among those with ' WD risk factors' and the reference category with no findings, depending on gender and occupational group. The lower limit of the 95% CI was at the lowest 2.0. In the Hurdle model, ' WD risk factors', SA days prior to the HRA and obesity were additive predictors for SA and/or the accumulated SA days in all occupational groups. Conclusion Self-reported health problems and obesity predict a higher total count of SA days in an additive fashion. These findings have implications for both management and the healthcare system in the prevention of WD. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
  • Laitinen, A.; Hagström, J.; Mustonen, H.; Kokkola, A.; Tervahartiala, T.; Sorsa, T.; Böckelman, C.; Haglund, C. (2018)
    Despite gastric cancer being rare nowadays in Western countries, it remains one of the leading causes of cancer death worldwide. The course of the disease varies, so the individual gastric cancer patient’s prognosis is difficult to determine. The need for new biomarkers is crucial. The aim of this study was to evaluate the prognostic value of serum matrix metalloproteinase-8, serum tissue inhibitor of metalloproteinase-1, and tissue matrix metalloproteinase-8 in patients with gastric cancer. Preoperative serum samples from 233 patients with gastric cancer were retrospectively analyzed. Serum levels of matrix metalloproteinase-8 were analyzed with immunofluorometric assay, and tissue inhibitor of metalloproteinase-1 levels were determined by enzyme-linked immunosorbent assay. We also determined the tissue expression of matrix metalloproteinase-8 in 276 gastric cancer samples by immunohistochemistry. Survival data and death causes came from patient records, the Population Register Center of Finland, and Statistics Finland. Patients with a low (131 ng/mL) serum matrix metalloproteinase-8 level had a considerably unfavorable prognosis (p = 0.002). Those patients with a high (≥170 ng/mL) serum tissue inhibitor of metalloproteinase-1 level also had a poor prognosis (p <0.001), and the latter remained significant in multivariable analysis (hazard ratio = 1.85; 95% confidence interval: 1.26–2.72; p = 0.002). The molar ratio of serum matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 levels with low (0.30) molar ratios predicted a worse prognosis (p = 0.020). Tissue matrix metalloproteinase-8 did not influence prognosis. These results suggest that serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase-1, and the ratio of matrix metalloproteinase-8/ tissue inhibitor of metalloproteinase-1 may prove useful biomarkers for prediction of prognosis in patients with gastric cancer. © The Author(s) 2018.
  • Koski, M.; Naukkarinen, H. (2017)
    Background: Obesity has a multifaceted etiology that involves genetic, biological and behavioral factors, body growth, eating habits, energy expenditure and the function of adipose tissue. The present study aimed to expand upon knowledge about the relationships among obesity, emotions and eating habits in severely obese individuals using a case-control method. Methods: The subject group consisted of 112 individuals (81 females and 31 males) receiving a permanent disability pension primarily for obesity. The control subjects were randomly selected from the same area and were receiving a disability pension for a different primary illness. The controls were matched with the subjects by the place of residence, sex, age, the time since the pension was granted and occupation. Psychiatric interviews were conducted on all participants. The results were analyzed using the chi-squared test (X2-test) and the percent distribution. The subject and control groups were compared using the t-test for paired variables. Conditional logistic regression analysis was also conducted. Results: The emotional state of eating was significantly associated with quarrels and feelings of loneliness. The subjects suffered from night eating syndrome, which was associated with an increased risk of early retirement. Binge eating syndrome was observed more frequently in the study group. The subjects reported feeling increased hunger compared with the controls. A significant percentage of the subjects had a body mass index of≥40. No differences in eating habits were observed between the groups. Conclusion: This study provides information on the relationship between emotions and eating habits in obesity, which is a rarely studied topic. We believe that our study provides a novel and necessary overview of the associations among severe obesity, emotions and eating habits. © The Author(s).