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  • Terevnikov, Viacheslav; Stenberg, Jan-Henry; Tiihonen, Jari; Burkin, Mark; Joffe, Grigori (2017)
    Aim: Sexual dysfunction, common in schizophrenia, may be further exaggerated by antipsychotics, especially those of First Generation (FGAs), and antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRs). Mirtazapine, an antidepressant characterized by its different action mechanism compared with that of the majority of other antidepressants, may improve SSRI-induced sexual dysfunction in patients with depression. It is unknown, however, whether mirtazapine improves sexual functioning in schizophrenia.Methods: This study randomly assigned FGA-treated patients with schizophrenia to receive either an add-on mirtazapine (n=20) or a placebo (n=19) for 6 weeks. Sexual functioning was prospectively measured using five relevant items from the Udvalg for Kliniske Undersogelser side-effect rating scale (UKU-SERS).Results: Orgasmic function improved with statistical significance in the mirtazapine group (p=.03), with no changes in any other sexual functions in either group.Conclusion: Add-on mirtazapine appears to relieve orgasmic dysfunction in FGA-treated patients with schizophrenia.
  • Moustgaard, Heta; Joutsenniemi, Kaisla; Myrskyla, Mikko; Martikainen, Pekka (2014)
  • Bazelier, Marloes T.; Eriksson, Irene; de Vries, Frank; Schmidt, Marjanka K.; Raitanen, Jani; Haukka, Jari; Starup-Linde, Jakob; De Bruin, Marie L.; Andersen, Morten (2015)
    PurposeTo identify pharmacoepidemiological multi-database studies and to describe data management and data analysis techniques used for combining data. MethodsSystematic literature searches were conducted in PubMed and Embase complemented by a manual literature search. We included pharmacoepidemiological multi-database studies published from 2007 onwards that combined data for a pre-planned common analysis or quantitative synthesis. Information was retrieved about study characteristics, methods used for individual-level analyses and meta-analyses, data management and motivations for performing the study. ResultsWe found 3083 articles by the systematic searches and an additional 176 by the manual search. After full-text screening of 75 articles, 22 were selected for final inclusion. The number of databases used per study ranged from 2 to 17 (median=4.0). Most studies used a cohort design (82%) instead of a case-control design (18%). Logistic regression was most often used for individual-level analyses (41%), followed by Cox regression (23%) and Poisson regression (14%). As meta-analysis method, a majority of the studies combined individual patient data (73%). Six studies performed an aggregate meta-analysis (27%), while a semi-aggregate approach was applied in three studies (14%). Information on central programming or heterogeneity assessment was missing in approximately half of the publications. Most studies were motivated by improving power (86%). ConclusionsPharmacoepidemiological multi-database studies are a well-powered strategy to address safety issues and have increased in popularity. To be able to correctly interpret the results of these studies, it is important to systematically report on database management and analysis techniques, including central programming and heterogeneity testing. (c) 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
  • Karppinen, Noora; Linden, Riikka; Sintonen, Harri; Tarkkanen, Maija; Roine, Risto; Heiskanen, Ilkka; Matikainen, Niina; Schalin-Jäntti, Camilla (2019)
    Background: The prevalence of small intestine neuroendocrine tumors (SI-NETs) is increasing. Disease progression is often slow and treatment options and long-term survival rates have improved, but little is known about health-related quality of life (HRQoL) in these patients. Objective: To assess HRQoL and its predictors in SI-NET patients receiving contemporary treatments. Methods: We measured HRQoL with 15D and SF-36 questionnaires in 134 SI-NET patients and compared the 15D results to those of an age- and gender-standardized sample of the general population (n = 1,153). In the patients, we studied the impact of treatments, Ki-67, liver metastases, circulating tumor markers, comorbidities, and/or socioeconomic factors on HRQoL with linear regression analysis. Results: The mean disease duration of the patients was 81 (4-468) months, 91% had metastatic disease, and 79% received somatostatin analog treatment. Hepatic tumor load was 0% in 44.8%, <10-25% in 44.0%, and > 25% in 11.2%, respectively. Mean fP-CgA and S-5HIAA concentrations were 15 (1.3-250) and 344 (24-7,470) nmol/L, respectively. Overall, HRQoL was significantly impaired in patients compared to controls (15D score 0.864 +/- 0.105 vs. 0.905 +/- 0.028, p <0.001). SI-NET patients scored worse on 9 of 15 dimensions: sleep, excretion (i. e., bladder and bowel function), depression, distress, vitality, sexual activity (p <0.001), breathing, usual activities, and discomfort and symptoms (p <0.01-0.05). SF-36 scores were impaired and highly correlated with 15D scores (p <0.001). HRQoL was impaired in patients with (n = 85) compared to patients without (n = 49) impaired excretion (0.828 vs. 0.933, p <0.001). In the patient group, number of medications predicted impaired HRQoL. Conclusions: Despite contemporary treatments, SI-NET patients have severely impaired HRQoL, including diarrhea, sleep, depression, vitality, and sexual activity. (c) 2018 S. Karger AG, Basel
  • Simoila, Laura; Isometsä, Erkki; Gissler, Mika; Suvisaari, Jaana; Halmesmäki, Erja; Lindberg, Nina (2018)
    Background: This national register-based study assesses obstetric and perinatal health outcomes in women with schizophrenia and their offspring. Methods: Using the Care Register for Health Care, we identified Finnish women who were born in 19651980 and diagnosed with schizophrenia. For each case, five age-and place-of-birth-matched controls were obtained from the Central Population Register of Finland. They were followed from the day when the disorder was diagnosed in specialized health-care (the index day) until 31.12.2013. Information related to births was obtained from the Medical Birth Register and the Register of Congenital Malformations. We focused on singleton pregnancies that led to a delivery after the index day. We restricted the analysis of deliveries in controls to those that occurred after the index day of the case. Maternal age, marital status, smoking status, sex of the newborn, and parity were used as covariates in adjusted models. Results: We identified 1162 singleton births among women with schizophrenia and 4683 among controls. Schizophrenic women had a 1.4-fold increased risk of induction of labor, delivery by cesarean section, and delivery by elective cesarean section. Regarding offspring, the risk of premature birth and the risk of low Apgar score at 1 min ( Conclusions: Schizophrenia associates with some specific delivery methods, but delivery complications are rare and their prevalence does not differ from that observed among community women. Maternal schizophrenia associates with some negative perinatal health outcomes of the offspring. (c) 2018 Elsevier Masson SAS. All rights reserved.
  • Ellfolk, Maria; Tornio, Aleksi; Niemi, Mikko; Leinonen, Maarit K.; Lahesmaa-Korpinen, Anna-Maria; Malm, Heli (2020)
    Aims P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are efflux transporters expressed in the placenta, limiting their substrates from reaching the foetus. Our aim was to investigate if concomitant prenatal exposure to several substrates or inhibitors of these transporters increases the risk of congenital anomalies. Methods The national Drugs and Pregnancy database, years 1996-2014, was utilized in this population-based birth cohort study. In the database, the Medical Birth Register, the Register on Induced Abortions, the Malformation register and the Register on Reimbursed Drug Purchases have been linked. The University of Washington Metabolism and Transport Drug Interaction Database was used to identify substrates and inhibitors of P-gp and BCRP. We included singleton pregnancies ending in birth or elective termination of pregnancy due to foetal anomaly. Known teratogens were excluded. We identified women exposed 1 month before pregnancy or during the first trimester to P-gp/BCRP polytherapy (n = 21 186); P-gp/breast cancer resistance protein monotherapy (n = 97 906); non-P-gp/BCRP polytherapy (n = 78 636); and unexposed (n = 728 870). We investigated the association between the exposure groups and major congenital anomalies using logistic regression adjusting for several confounders. Results The prevalence of congenital anomalies was higher in the P-gp/BCRP polytherapy group (5.5%) compared to the P-gp/BCRP monotherapy (4.7%, OR 1.13; 95% CI 1.05-1.21), the non-P-gp/BCRP polytherapy (4.9%, OR 1.14; 95% CI 1.06-1.22), and to the unexposed groups (4.2%, OR 1.23; 95% CI 1.15-1.31). Conclusion The results suggest a role of placental transporter-mediated drug interactions in teratogenesis.
  • Huhtakangas, Juha; Lopponen, Pekka; Tetri, Sami; Juvela, Seppo; Saloheimo, Pertti; Bode, Michaela K.; Hillbom, Matti (2013)