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  • He, Chen; Micallef, Luana; Tanoli, Zia-ur-Rehman; Kaski, Samuel; Aittokallio, Tero; Jacucci, Giulio (BioMed Central, 2017)
    Abstract Background Dispersed biomedical databases limit user exploration to generate structured knowledge. Linked Data unifies data structures and makes the dispersed data easy to search across resources, but it lacks supporting human cognition to achieve insights. In addition, potential errors in the data are difficult to detect in their free formats. Devising a visualization that synthesizes multiple sources in such a way that links between data sources are transparent, and uncertainties, such as data conflicts, are salient is challenging. Results To investigate the requirements and challenges of uncertainty-aware visualizations of linked data, we developed MediSyn, a system that synthesizes medical datasets to support drug treatment selection. It uses a matrix-based layout to visually link drugs, targets (e.g., mutations), and tumor types. Data uncertainties are salient in MediSyn; for example, (i) missing data are exposed in the matrix view of drug-target relations; (ii) inconsistencies between datasets are shown via overlaid layers; and (iii) data credibility is conveyed through links to data provenance. Conclusions Through the synthesis of two manually curated datasets, cancer treatment biomarkers and drug-target bioactivities, a use case shows how MediSyn effectively supports the discovery of drug-repurposing opportunities. A study with six domain experts indicated that MediSyn benefited the drug selection and data inconsistency discovery. Though linked publication sources supported user exploration for further information, the causes of inconsistencies were not easy to find. Additionally, MediSyn could embrace more patient data to increase its informativeness. We derive design implications from the findings.
  • Hallamies, Sanna; Pelttari, Liisa M; Poikonen-Saksela, Paula; Jekunen, Antti; Jukkola-Vuorinen, Arja; Auvinen, Päivi; Blomqvist, Carl; Aittomäki, Kristiina; Mattson, Johanna; Nevanlinna, Heli (BioMed Central, 2017)
    Abstract Background Several susceptibility genes have been established for female breast cancer, of which mutations in BRCA1 and especially in BRCA2 are also known risk factors for male breast cancer (MBC). The role of other breast cancer genes in MBC is less well understood. Methods In this study, we have genotyped 68 MBC patients for the known breast or ovarian cancer associated mutations in the Finnish population in CHEK2, PALB2, RAD51C, RAD51D, and FANCM genes. Results CHEK2 c.1100delC mutation was found in 4 patients (5.9%), which is significantly more frequent than in the control population (OR: 4.47, 95% CI 1.51–13.18, p = 0.019). Four CHEK2 I157T variants were also detected, but the frequency did not significantly differ from population controls (p = 0.781). No RAD51C, RAD51D, PALB2, or FANCM mutations were found. Conclusions These data suggest that the CHEK2 c.1100delC mutation is associated with an increased risk for MBC in the Finnish population.
  • Khattab, Ayman; Jylhä, Kaisa; Hakala, Tomi; Aalto, Mikko; Malima, Robert; Kisinza, William; Honkala, Markku; Nousiainen, Pertti; Meri, Seppo (BioMed Central, 2017)
    Abstract Background Mosquitoes are vectors for many diseases such as malaria. Insecticide-treated bed nets and indoor residual spraying of insecticides are the principal malaria vector control tools used to prevent malaria in the tropics. Other interventions aim at reducing man-vector contact. For example, house screening provides additive or synergistic effects to other implemented measures. We used commercial screen materials made of polyester, polyethylene or polypropylene to design novel mosquito screens that provide remarkable additional benefits to those commonly used in house screening. The novel design is based on a double screen setup made of a screen with 3D geometric structures parallel to a commercial mosquito screen creating a trap between the two screens. Owing to the design of the 3D screen, mosquitoes can penetrate the 3D screen from one side but cannot return through the other side, making it a unidirectional mosquito screen. Therefore, the mosquitoes are trapped inside the double screen system. The permissiveness of both sides of the 3D screens for mosquitoes to pass through was tested in a wind tunnel using the insectary strain of Anopheles stephensi. Results Among twenty-five tested 3D screen designs, three designs from the cone, prism, or cylinder design groups were the most efficient in acting as unidirectional mosquito screens. The three cone-, prism-, and cylinder-based screens allowed, on average, 92, 75 and 64% of Anopheles stephensi mosquitoes released into the wind tunnel to penetrate the permissive side and 0, 0 and 6% of mosquitoes to escape through the non-permissive side, respectively. Conclusions A cone-based 3D screen fulfilled the study objective. It allowed capturing 92% of mosquitoes within the double screen setup inside the wind tunnel and blocked 100% from escaping. Thus, the cone-based screen effectively acted as a unidirectional mosquito screen. This 3D screen-based trap design could therefore be used in house screening as a means of avoiding infective bites and reducing mosquito population size.
  • Kinnunen, Pete T T; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo L J; Auvinen, Anssi (BioMed Central, 2017)
    Abstract Background Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease. Methods The study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias. Results In total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant non-users, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1.13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death. Conclusions We found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.
  • Määttä, Suvi; Kaukonen, Riikka; Vepsäläinen, Henna; Lehto, Elviira; Ylönen, Anna; Ray, Carola; Erkkola, Maijaliisa; Roos, Eva (BioMed Central, 2017)
    Abstract Background Previous studies suggest that preschoolers from low socioeconomic backgrounds engage in more screen time. Still, the factors in the social and physical home environment driving these differences in preschool children’s screen time are poorly understood. This study examines potential home environment mediators in the associations between parental educational level and preschoolers’ screen time. Methods A total of 864 children aged 3–6 years and their parents participated in a cross-sectional DAGIS study in 2015–2016. Parents recorded their children’s screen time in a diary (N = 823). For the analyses, the daily average screen time at home was calculated. Parental questionnaires (N = 808) assessed educational level and eight social and physical environment factors in the home (i.e., descriptive norm for children’s screen time, parental screen use in front of children, parental importance for limiting children’s screen time, parental attitude toward societal pressures for children’s screen time, access to screens at home, parental self-efficacy for limiting children’s screen time, satisfaction of children’s screen time, and rules for limiting children’s screen time). Parental education was grouped into low, middle, and high education. The associations were tested by conducting mediation analyses adjusted by season and children’s sex and age. The significant mediators in the single-mediator models were included in the final multiple-mediator models. Results Of the potential eight mediators, the following four had a significant indirect association: descriptive norm for children’s screen time, parental screen use in front of children, parental importance for limiting children’s screen time, and parental attitude toward societal pressures for children’s screen time. Parents with high education had lower descriptive norm and used fewer screens in front of children compared to parents with middle or low education, and in turn, these factors were associated with less screen time among children from parents with a higher education level. Parents with high education placed greater importance on limiting children’s screen time and felt less societal pressures about children’s screen time compared to parents with low education, and in turn, these factors were associated with less screen time among children from parents with a higher education level. Conclusions Our study recognized multiple modifiable mediators in the associations between parental education and preschool children’s screen time. When aiming to diminish socioeconomic status differences in preschool children’s screen time, the focus should be on parental role models, attitudes, and norm related to children’s screen time.
  • Haimi-Hakala, Minna; Hälli, Outi; Laurila, Tapio; Raunio-Saarnisto, Mirja; Nokireki, Tiina; Laine, Taina; Nykäsenoja, Suvi; Pelkola, Kirsti; Segales, Joaquim; Sibila, Marina; Oliviero, Claudio; Peltoniemi, Olli; Pelkonen, Sinikka; Heinonen, Mari (BioMed Central, 2017)
    Abstract Background The objective of our study was to clinically and etiologically investigate acute outbreaks of respiratory disease in Finland. Our study also aimed to evaluate the clinical use of various methods in diagnosing respiratory infections under field conditions and to describe the antimicrobial resistance profile of the main bacterial pathogen(s) found during the study. Methods A total of 20 case herds having finishing pigs showing acute respiratory symptoms and eight control herds showing no clinical signs suggesting of respiratory problems were enrolled in the study. Researchers visited each herd twice, examining and bleeding 20 pigs per herd. In addition, nasal swab samples were taken from 20 pigs and three pigs per case herd were necropsied during the first visit. Serology was used to detect Actinobacillus pleuropneumoniae (APP), swine influenza virus (SIV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine respiratory coronavirus (PRCV) and Mycoplasma hyopneumoniae antibodies. Polymerase chain reaction (PCR) was used to investigate the presence of porcine circovirus type 2 (PCV2) in serum and SIV in the nasal and lung samples. Pathology and bacteriology, including antimicrobial resistance determination, were performed on lung samples obtained from the field necropsies. Results According to the pathology and bacteriology of the lung samples, APP and Ascaris suum were the main causes of respiratory outbreaks in 14 and three herds respectively, while the clinical signs in three other herds had a miscellaneous etiology. SIV, APP and PCV2 caused concurrent infections in certain herds but they were detected serologically or with PCR also in control herds, suggesting possible subclinical infections. APP was isolated from 16 (80%) case herds. Marked resistance was observed against tetracycline for APP, some resistance was detected against trimethoprim/sulfamethoxazole, ampicillin and penicillin, and no resistance against florfenicol, enrofloxacin, tulathromycin or tiamulin was found. Serology, even from paired serum samples, gave inconclusive results for acute APP infection diagnosis. Conclusions APP was the most common cause for acute respiratory outbreaks in our study. SIV, A. suum, PCV2 and certain opportunistic bacteria were also detected during the outbreaks; however, viral pathogens appeared less important than bacteria. Necropsies supplemented with microbiology were the most efficient diagnostic methods in characterizing the studied outbreaks.
  • Gracia, Ibon E; Rondón, Carmen; Campo, Paloma; Prieto, Ana; Mayorga, Lina; Galindo, Luisa; Molina, Ana; Blanca, Miguel; Torres, Maria J; Morikawa, Taiyo; Fukuoka, Ayumi; Matsushita, Kazufumi; Fujieda, Shigeharu; Yoshimoto, Tomohiro; Iwasaki, Naruhito; Smulders, Tamar; Van Egmond, Danielle; Van Drunen, Kees; Van Der Schee, Marc; Beule, Achim G; Berings, Margot; Jult, Anton; Vermeulen, Hanne; De Ruyck, Natalie; Derycke, Lara; Ucar, Hakan; Ghekiere, Philip; Temmerman, Robin; Ellis, John; Bachert, Claus; Lambrecht, Bart; Dullaers, Melissa; Gevaert, Philippe; Arasi, Stefania; Perna, Serena; Resch, Yvonne; Lupinek, Christian; Chen, Kuan-Wei; Vrtala, Susanne; Valenta, Rudolf; Matricardi, Paolo M; Gonçalves, Ivânia; Jacinto, Tiago; Amaral, Rita; Pereira, Ana M; Araújo, Luís M; Couto, Mariana; Fonseca, João A; Stjarne, Par; Kaulsay, Ranbir; Pohl, Wolfgang; Plaza, Maria C; Prieto, Ana M; Mayorga, Cristobalina; Herknerova, Magdalena; Wang, Tengchin; Wu, Chiejun; Kilimajer, Jonathan; Pujols, Laura; Roca-Ferrer, Jordi; Callejas, Borja; Fuentes-Prado, Mireya; Perez-Gonzalez, Maria; Alobid, Isam; Valero, Antonio; Picado, Cesar; Murray, Ruth; Mullol, Joaquim; Steelant, Brecht; Martens, Katleen; Boeckxstaens, Guy; Seys, Sven F; Hellings, Peter W; Biggs, Timothy C; Hayes, Stephen M; Harries, Philip G; Pender, Sylvia; Salib, Rami J; Kim, Jean; Lee, Hyun S; Kalogjera, Livije; Vrkic, Nada; Topic, Anita; Tomljenovic, Dejan; Greguric, Tomislav; Radovanovic, Patricija B; Jund, Rainer; Haimerl, Pascal; Chaker, Adam M; Schober, Yvonne; Schindela, Sonja; Nockher, Andreas; Schmidt-Weber, Carsten B; Bieren, Julia E; Ickrath, Pascal; Kleinsasser, Norbert; Beyersdorf, Niklas; Ding, Xin; Hagen, Rudolf; Hackenberg, Stephan; Cangiano, Daniela; Cinetto, Francesco; Brescia, Giuseppe; Marioni, Gino; Zanotti, Claudia; Schiavon, Franco; Padoan, Roberto; Caputo, Ilaria; Neri, Raffaella; Agostini, Carlo; Kim, Ji H; Jang, Yong J; Lim, Ji Y; Kim, Sung H; Savlevich, Elena; Gaganov, Leonid; Kochnova, Maria; Egorov, Victor; Fok, Jie S; Hanif, Tanzeela; Renkonen, Jutta; Joenväärä, Sakari; Kankainen, Matti; Mäkelä, Mika; Kauppi, Paula; Pelkonen, Anna; Mattila, Pirkko; Renkonen, Risto; Toppila-Salmi, Sanna; Holtappels, Gabriele; Lambrecht, Bart N; Blanca-López, Natalia; Gonzalez-Visiedo, Miguel; Jurado, Raquel; Canto, Gabriela (BioMed Central, 2017)
  • Pekkala, Johanna; Blomgren, Jenni; Pietiläinen, Olli; Lahelma, Eero; Rahkonen, Ossi (BioMed Central, 2017)
    Abstract Background Musculoskeletal diseases and mental disorders are major causes of long-term sickness absence in Western countries. Although sickness absence is generally more common in lower occupational classes, little is known about class differences in diagnostic-specific absence over time. Focusing on Finland during 2005–2014, we therefore set out to examine the magnitude of and changes in absolute and relative occupational class differences in long-term sickness absence due to major diagnostic causes. Methods A 70-per-cent random sample of Finns aged 25–64 linked to register data on medically certified sickness absence (of over 10 working days) in 2005–2014 was retrieved from the Social Insurance Institution of Finland. Information on occupational class was obtained from Statistics Finland and linked to the data. The study focused on female (n = 658,148–694,142) and male (n = 604,715–642,922) upper and lower non-manual employees and manual workers. The age-standardised prevalence, the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII) were calculated for each study year to facilitate examination of the class differences. Results The prevalence of each diagnostic cause of sickness absence declined during the study period, the most common causes being musculoskeletal diseases, mental disorders and injuries. The prevalence of other causes under scrutiny was less than 1 % annually. By far the largest absolute and relative differences were in musculoskeletal diseases among both women and men. Moreover, the absolute differences in both genders (p < 0.0001) and the relative differences in men (p < 0.0001) narrowed over time as the prevalence declined most among manual workers. Both genders showed modest and stable occupational class differences in mental disorders. In the case of injuries, no major changes occurred in absolute differences but relative differences narrowed over time in men (p < 0.0001) due to a strong decline in prevalence among manual workers. Class differences in the other studied diagnostic causes under scrutiny appeared negligible. Conclusions By far the largest occupational class differences in long-term sickness absence concerned musculoskeletal diseases, followed by injuries. The results highlight potential targets for preventive measures aimed at reducing sickness absence and narrowing class differences in the future.
  • Wang, Yafei; Yu, Dongsheng; Liu, Zhiming; Zhou, Fang; Dai, Jun; Wu, Bingbing; Zhou, Jing; Heng, Boon C; Zou, Xiao H; Ouyang, Hongwei; Liu, Hua (BioMed Central, 2017)
    Abstract Background Mesenchymal stem cell therapy for osteoarthritis (OA) has been widely investigated, but the mechanisms are still unclear. Exosomes that serve as carriers of genetic information have been implicated in many diseases and are known to participate in many physiological processes. Here, we investigate the therapeutic potential of exosomes from human embryonic stem cell-induced mesenchymal stem cells (ESC-MSCs) in alleviating osteoarthritis (OA). Methods Exosomes were harvested from conditioned culture media of ESC-MSCs by a sequential centrifugation process. Primary mouse chondrocytes treated with interleukin 1 beta (IL-1β) were used as an in vitro model to evaluate the effects of the conditioned medium with or without exosomes and titrated doses of isolated exosomes for 48 hours, prior to immunocytochemistry or western blot analysis. Destabilization of the medial meniscus (DMM) surgery was performed on the knee joints of C57BL/6 J mice as an OA model. This was followed by intra-articular injection of either ESC-MSCs or their exosomes. Cartilage destruction and matrix degradation were evaluated with histological staining and OARSI scores at the post-surgery 8 weeks. Results We found that intra-articular injection of ESC-MSCs alleviated cartilage destruction and matrix degradation in the DMM model. Further in vitro studies illustrated that this effect was exerted through ESC-MSC-derived exosomes. These exosomes maintained the chondrocyte phenotype by increasing collagen type II synthesis and decreasing ADAMTS5 expression in the presence of IL-1β. Immunocytochemistry revealed colocalization of the exosomes and collagen type II-positive chondrocytes. Subsequent intra-articular injection of exosomes derived from ESC-MSCs successfully impeded cartilage destruction in the DMM model. Conclusions The exosomes from ESC-MSCs exert a beneficial therapeutic effect on OA by balancing the synthesis and degradation of chondrocyte extracellular matrix (ECM), which in turn provides a new target for OA drug and drug-delivery system development.
  • Qadri, Sami; Anttonen, Olli; Viikilä, Juho; Seppälä, Eija H; Myllykangas, Samuel; Alastalo, Tero-Pekka; Holmström, Miia; Heliö, Tiina; Koskenvuo, Juha W (BioMed Central, 2017)
    Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disease, involving changes in ventricular myocardial tissue and leading to fatal arrhythmias. Mutations in desmosomal genes are thought to be the main cause of ARVC. However, the exact molecular genetic etiology of the disease still remains largely inconclusive, and this along with large variabilities in clinical manifestations complicate clinical diagnostics. Case presentation We report two families (n = 20) in which a desmoglein-2 (DSG2) missense variant c.1003A > G, p.(Thr335Ala) was discovered in the index patients using next-generation sequencing panels. The presence of this variant in probands’ siblings and children was studied by Sanger sequencing. Five homozygotes and nine heterozygotes were found with the mutation. Participants were evaluated clinically where possible, and available medical records were obtained. All patients homozygous for the variant fulfilled the current diagnostic criteria for ARVC, whereas none of the heterozygous subjects had symptoms suggestive of ARVC or other cardiomyopathies. Conclusions The homozygous DSG2 variant c.1003A > G co-segregated with ARVC, indicating autosomal recessive inheritance and complete penetrance. More research is needed to establish a detailed understanding of the relevance of rare variants in ARVC associated genes, which is essential for informative genetic counseling and rational family member testing.
  • Winther, Stine B; Österlund, Pia; Berglund, Åke; Glimelius, Bengt; Qvortrup, Camilla; Sorbye, Halfdan; Pfeiffer, Per (BioMed Central, 2017)
    Abstract Background Metastatic colorectal cancer (mCRC) is a disease of older age, but there is a relative lack of knowledge about effects of chemotherapy in older patients as they are under-represented in clinical trials. Little data can guide whether the strategy in older mCRC patients should be a sequential full-dose monotherapy chemotherapy approach or a dose-reduced combination chemotherapy approach. The oral 5FU prodrug S-1 seems to have less side effects than capecitabine and should be an optimal drug for older patients, but few data are available. Improved geriatric assessments are needed to select which older patients should receive therapy. Methods The NORDIC 9 trial is a Nordic multicenter randomized phase II study comparing full dose monotherapy (S-1 30 mg/m2 twice daily days 1–14 every 3 weeks, followed by second line irinotecan 250–350 mg/m2 iv day 1 every 3 weeks or 180–250 mg/m2 iv day 1 every 2 weeks) with reduced dose combination therapy (S-1 20 mg/m2 days 1–14 + oxaliplatin 100 mg/m2 iv day 1 every 3 weeks, followed by second line S-1 20 mg/m2 days 1–14 + irinotecan 180 mg/m2 day 1 every 3 week) for older patients (≥70 years) with mCRC who are not candidates for full-dose standard combination therapy. Additional bevacizumab (7.5 mg/kg) is optional in first-line. Blood samples and tumor tissue will be collected to investigate predictive markers. Geriatric screening tools (G-8, VES-13, Timed-Up-and-Go and Handgrip strength), Charlson Comorbidty Index and quality of life (EORTC QLQ-C30) will be evaluated as predictors of efficacy and toxicity. The target sample size is 150 patients. The primary endpoint is progression-free survival and secondary endpoints are time-to-failure of strategy, overall survival, response rate, toxicity, and correlations between biomarkers, pre-treatment characteristics and geriatric assessments. Discussion The study will add knowledge on how to treat older mCRC patients who are not candidates for standard combination therapy. Furthermore it may provide understanding of efficacy and tolerability of chemotherapy in older cancer patients and thus offer a better chance for tailored treatment strategies in these patients. Trial registration EU Clinical Trial Register, EudraCT no. 2014–000394-39 . Registered 05 May 2014.
  • Kumar, Ashwini; Kankainen, Matti; Parsons, Alun; Kallioniemi, Olli; Mattila, Pirkko; Heckman, Caroline A (BioMed Central, 2017)
    Abstract Background RNA sequencing (RNA-seq) has become an indispensable tool to identify disease associated transcriptional profiles and determine the molecular underpinnings of diseases. However, the broad adaptation of the methodology into the clinic is still hampered by inconsistent results from different RNA-seq protocols and involves further evaluation of its analytical reliability using patient samples. Here, we applied two commonly used RNA-seq library preparation protocols to samples from acute leukemia patients to understand how poly-A-tailed mRNA selection (PA) and ribo-depletion (RD) based RNA-seq library preparation protocols affect gene fusion detection, variant calling, and gene expression profiling. Results Overall, the protocols produced similar results with consistent outcomes. Nevertheless, the PA protocol was more efficient in quantifying expression of leukemia marker genes and showed better performance in the expression-based classification of leukemia. Independent qRT-PCR experiments verified that the PA protocol better represented total RNA compared to the RD protocol. In contrast, the RD protocol detected a higher number of non-coding RNA features and had better alignment efficiency. The RD protocol also recovered more known fusion-gene events, although variability was seen in fusion gene predictions. Conclusion The overall findings provide a framework for the use of RNA-seq in a precision medicine setting with limited number of samples and suggest that selection of the library preparation protocol should be based on the objectives of the analysis.
  • Pihlajamäki, Harri K; Parviainen, Mickael C; Kautiainen, Hannu; Kiviranta, Ilkka (BioMed Central, 2017)
    Abstract Background Musculoskeletal disorders and injuries are common causes of morbidity and loss of active, physically demanding training days in military populations. We evaluated the incidence, diagnosis, and risk factors of knee disorders and injuries in male Finnish military conscripts. Methods The study population comprised 5 cohorts of 1000 men performing their military service, classified according to birth year (1969, 1974, 1979, 1984, and 1989). Follow-up time for each conscript was the individual conscript’s full, completed military service period. Data for each man were collected from a standard pre-information questionnaire used by defense force healthcare officials and from all original medical reports of the garrison healthcare centers. Background variables for risk factor analysis included the conscripts’ service data, i.e., service class (A, B), length of military service, age, height, weight, body mass index (BMI), underweight, overweight, obesity, smoking habit, education, diseases, injuries, and subjective symptoms. Results Of the 4029 conscripts, 853 visited healthcare professionals for knee symptoms during their military service, and 103 of these had suffered a knee injury. Independent risk factors for the incidence of knee symptoms were: older age; service class A; overweight (BMI 25.0–29.9 kg/m2); smoking habit; comprehensive school education only; and self-reported previous symptoms of the musculoskeletal, respiratory, and gastrointestinal system. The majority of visits to garrison healthcare services due to knee symptoms occurred during the first few months of military service. Knee symptoms were negatively correlated with self-reported mental and behavioral disorders. Conclusions The present study highlights the frequency of knee disorders and injuries in young men during physically demanding military training. One-fifth of the male conscripts visited defense force healthcare professionals due to knee symptoms during their service period. Independent risk factors for the incidence of knee symptoms during military service were age at military service; military service class A; overweight; smoking habit; comprehensive school education only; and self-reported previous symptoms of the musculoskeletal system, respiratory system, or gastrointestinal system. These risk factors should be considered when planning and implementing procedures to reduce knee disorders and injuries during compulsory military service.
  • Taipale, Heidi; Koponen, Marjaana; Tanskanen, Antti; Lavikainen, Piia; Sund, Reijo; Tiihonen, Jari; Hartikainen, Sirpa; Tolppanen, Anna-Maija (BioMed Central, 2017)
    Abstract Background Antidepressant use has been associated with an increased risk of falling, but no studies have been conducted on whether antidepressant use is associated with an increased risk of head injuries which often result from falling among older persons. The objective of this study was to investigate the risk of head and brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer’s disease. Methods A matched cohort study was conducted by comparing new antidepressant users (n = 10,910) with two matched nonusers (n = 21,820) in the MEDALZ study cohort. The MEDALZ cohort includes all community-dwelling persons newly diagnosed with Alzheimer’s disease between 2005 and 2011 in Finland. Incident antidepressant users were identified based on register-based dispensing data from the Prescription register with a 1-year washout period for antidepressant use. Nonusers were matched with users based on age, gender, and time since Alzheimer’s disease diagnosis. The outcome events were defined as any head injuries and traumatic brain injuries based on diagnoses in Hospital Discharge and Causes of Death registers. Propensity score adjusted Cox proportional hazard models were utilized. Sensitivity analyses with case-crossover design were conducted. All registers are linkable with unique personal identification numbers assigned for each resident. Results Antidepressant use was associated with an increased risk of head injuries (age-adjusted event rate per 100 person-years 2.98 (95% confidence interval (CI) 2.49–3.06) during use and 2.43 (95% CI 2.06–2.35) during nonuse, adjusted hazard ratio (HR) 1.35, 95% CI 1.20–1.52) and traumatic brain injuries (age-adjusted event rate per 100 person-years 1.33 (95% CI 1.13–1.53) during use and 1.10 (95% CI 1.00–1.20) during nonuse, adjusted HR 1.26, 95% CI 1.06–1.50). The risk was highest during the first 30 days of use (HR 1.71, 95% CI 1.10–2.66 for head injuries; HR 2.06, 95% CI 1.12–3.82 for traumatic brain injuries) and remained at an elevated level for head injuries for over 2 years of use. In case-crossover analyses, antidepressant use was consistently associated with a higher risk of head injuries. Conclusions Antidepressant use was associated with an increased risk of the most severe outcomes, head and brain injuries, in persons with Alzheimer’s disease. Antidepressant use should be carefully considered and the association confirmed in future studies.
  • Nordgren, Heli; Vapalahti, Katariina; Vapalahti, Olli; Sukura, Antti; Virtala, Anna-Maija (BioMed Central, 2017)
    Abstract Background In 2007, a previously unrecorded disease, fur animal epidemic necrotic pyoderma (FENP), was detected in farmed mink (Neovision vision), foxes (Vulpes lagopus) and Finnraccoons (Nyctereutes procyonoides) in Finland. Symptoms included severe pyoderma with increased mortality, causing both animal welfare problems and economic losses. In 2011, an epidemiologic questionnaire was mailed to all members of the Finnish Fur Breeders’ Association to assess the occurrence of FENP from 2009 through the first 6 months of 2011. The aim was to describe the geographical distribution and detailed clinical signs of FENP, as well as sources of infection and potential risk factors for the disease. Results A total of 239 farmers (25%) returned the questionnaire. Clinical signs of FENP were observed in 40% (95% CI 34–46%) of the study farms. In addition, the survey clarified the specific clinical signs for different animal species. The presence of disease was associated with the importation of mink, especially from Denmark (OR 9.3, 95% CI 2.6–33.0). The transmission route between Finnish farms was associated with fur animal purchases. Some risk factors such as the farm type were also indicated. As such, FENP was detected more commonly on farms with more than one species of fur animal in comparison to farms with, for example, only foxes (OR 4.6, 95% CI 2.4–8.6), and the incidence was higher on farms with over 750 breeder mink compared to smaller farms (OR 3.8, 95% CI 1.6–9.0). Contact between fur animals and birds and other wildlife increased the risk of FENP on farms. Responses also indicated that blocking the entry of wildlife to the animal premises protected against FENP. Conclusions FENP was most likely introduced to Finland by imported mink and spread further within the country via domestically purchased fur animals. Some potential risk factors, such as the type and size of the farm and contact with wildlife, contributed to the spread of FENP. Escape-proof shelter buildings block the entry of wildlife, thus protecting fur animals against FENP.