Publications by authors named "S Kurki"

55 Publications

Carbonic anhydrase inhibitors suppress seizures in a rat model of birth asphyxia.

Epilepsia 2021 Jun 27. Epub 2021 Jun 27.

Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences, University of Helsinki, Helsinki, Finland.

Objective: Seizures are common in neonates recovering from birth asphyxia but there is general consensus that current pharmacotherapy is suboptimal and that novel antiseizure drugs are needed. We recently showed in a rat model of birth asphyxia that seizures are triggered by the post-asphyxia recovery of brain pH. Here our aim was to investigate whether carbonic anhydrase inhibitors (CAIs), which induce systemic acidosis, block the post-asphyxia seizures.

Methods: The CAIs acetazolamide (AZA), benzolamide (BZA), and ethoxzolamide (EZA) were administered intraperitoneally or intravenously to 11-day-old rats exposed to intermittent asphyxia (30 min; three 7+3 min cycles of 9% and 5% O at 20% CO ). Electrode measurements of intracortical pH, Po , and local field potentials (LFPs) were made under urethane anesthesia. Convulsive seizures and blood acid-base parameters were examined in freely behaving animals.

Results: The three CAIs decreased brain pH by 0.14-0.17 pH units and suppressed electrographic post-asphyxia seizures. AZA, BZA, and EZA differ greatly in their lipid solubility (EZA > AZA > BZA) and pharmacokinetics. However, there were only minor differences in the delay (range 0.8-3.7 min) from intraperitoneal application to their action on brain pH. The CAIs induced a modest post-asphyxia elevation of brain Po that had no effect on LFP activity. AZA was tested in freely behaving rats, in which it induced a respiratory acidosis and decreased the incidence of convulsive seizures from 9 of 20 to 2 of 17 animals.

Significance: AZA, BZA, and EZA effectively block post-asphyxia seizures. Despite the differences in their pharmacokinetics, they had similar effects on brain pH, which indicates that their antiseizure mode of action was based on respiratory (hypercapnic) acidosis resulting from inhibition of blood-borne and extracellular vascular carbonic anhydrases. AZA has been used for several indications in neonates, suggesting that it can be safely repurposed for the treatment of neonatal seizures as an add-on to the current treatment regimen.
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http://dx.doi.org/10.1111/epi.16963DOI Listing
June 2021

Impact of deep learning-determined smoking status on mortality of cancer patients: never too late to quit.

ESMO Open 2021 Jun 3;6(3):100175. Epub 2021 Jun 3.

University of Turku, Turku, Finland; Department of Oncology, Turku University Hospital, Turku, Finland; FICAN West Cancer Centre, Turku, Finland. Electronic address:

Background: Persistent smoking after cancer diagnosis is associated with increased overall mortality (OM) and cancer mortality (CM). According to the 2020 Surgeon General's report, smoking cessation may reduce CM but supporting evidence is not wide. Use of deep learning-based modeling that enables universal natural language processing of medical narratives to acquire population-based real-life smoking data may help overcome the challenge. We assessed the effect of smoking status and within-1-year smoking cessation on CM by an in-house adapted freely available language processing algorithm.

Materials And Methods: This cross-sectional real-world study included 29 823 patients diagnosed with cancer in 2009-2018 in Southwest Finland. The medical narrative, International Classification of Diseases-10th edition codes, histology, cancer treatment records, and death certificates were combined. Over 162 000 sentences describing tobacco smoking behavior were analyzed with ULMFiT and BERT algorithms.

Results: The language model classified the smoking status of 23 031 patients. Recent quitters had reduced CM [hazard ratio (HR) 0.80 (0.74-0.87)] and OM [HR 0.78 (0.72-0.84)] compared to persistent smokers. Compared to never smokers, persistent smokers had increased CM in head and neck, gastro-esophageal, pancreatic, lung, prostate, and breast cancer and Hodgkin's lymphoma, irrespective of age, comorbidities, performance status, or presence of metastatic disease. Increased CM was also observed in smokers with colorectal cancer, men with melanoma or bladder cancer, and lymphoid and myeloid leukemia, but no longer independently of the abovementioned covariates. Specificity and sensitivity were 96%/96%, 98%/68%, and 88%/99% for never, former, and current smokers, respectively, being essentially the same with both models.

Conclusions: Deep learning can be used to classify large amounts of smoking data from the medical narrative with good accuracy. The results highlight the detrimental effects of persistent smoking in oncologic patients and emphasize that smoking cessation should always be an essential element of patient counseling.
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http://dx.doi.org/10.1016/j.esmoop.2021.100175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182259PMC
June 2021

The burden of hip and knee osteoarthritis in Finnish occupational healthcare.

BMC Musculoskelet Disord 2021 May 29;22(1):501. Epub 2021 May 29.

Terveystalo Kamppi, Jaakonkatu 3, 00100, Helsinki, Finland.

Background: Osteoarthritis (OA) is a leading cause of disability and pain especially among older adults, but it is also known to affect working age individuals, often leading to reduced productivity and increased healthcare usage. The aim of this study was to determine the burden of hip and knee OA in Finnish occupational healthcare.

Methods: This was a retrospective registry study utilizing the electronic medical records of the largest private and occupational healthcare provider in Finland. All consented patients with hip or knee OA were identified. A subcohort of occupational healthcare (OCH) patients was then compared to an age- and gender-matched control group without OA. Patient demographics including comorbidities were determined and healthcare contacts, medication prescriptions, and sick leaves were compared between the two groups. The study period was from January 1st, 2012 to April 30th, 2020.

Results: 51,068 patients with hip or knee OA were identified (all OA cohort) and 35,109 of these formed the occupational healthcare subcohort. Most of the OA patients were female and belonged to the age group 50-59 years. The point prevalence of hip/knee OA at the end of the study period was 5.6% for the occupational healthcare subcohort. OA patients had 2.2 times more healthcare contacts and 2.8 times more overall sick leave days compared to the age- and gender-matched control cohort. Etoricoxib was the most commonly prescribed medication at OA-related visits (21.8% of patients). Opioids were prescribed to 10.6% of patients at OA-related visits and the most prescribed opioid was a combination of codeine and paracetamol (4.8% of patients). 5054 OA patients (14.4%) had a contraindication for non-steroidal anti-inflammatory drugs (NSAIDs).

Conclusions: This retrospective registry study utilizing real-world data provides new evidence on the disease burden of hip or knee osteoarthritis from the electronic medical records of Finnish occupational healthcare customers. OA patients had more comorbidities, more healthcare contacts, more sick leave days, and more analgesic prescriptions compared to an age- and gender-matched control cohort without OA.
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http://dx.doi.org/10.1186/s12891-021-04372-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164770PMC
May 2021

Increased Risk of Parkinson's Disease in Patients With Schizophrenia Spectrum Disorders.

Mov Disord 2021 06 6;36(6):1353-1361. Epub 2021 Jan 6.

Clinical Neurosciences, University of Turku and Neurocenter, Turku University Hospital, Turku, Finland.

Background: PD comorbid with schizophrenia has been considered rare because these diseases associate with opposite alterations in the brain dopamine system. The objective of this study was to investigate the risk of PD after a diagnosis of a schizophrenia spectrum disorder.

Methods: Regionally, this was a retrospective record-based case-control study. The cohort included 3045 PD patients treated 2004-2019 in southwestern Finland. Nationally this was a nested case-control study using registers to examine Finnish patients who received a clinically confirmed PD diagnosis 1996-2015 (n = 22,189). PD patients with previously diagnosed schizophrenia spectrum disorder (separate analysis for schizophrenia) were included. Comparable non-PD control groups were derived from both data sets. All PD diagnoses were based on individual clinical examinations by certified neurologists.

Results: In PD patients, the prevalence of earlier schizophrenia spectrum disorder was 0.76% in regional data and 1.50% in nationwide data. In age-matched controls, the prevalence in the regional and national data was 0.16% and 1.31%, respectively. The odds ratio for PD after schizophrenia spectrum disorder diagnosis was 4.63 (95% CI, 1.76-12.19; P < 0.01) in the regional data and 1.17 (95% CI, 1.04-1.31; P < 0.01) in the national data.

Conclusions: Schizophrenia spectrum disorder increases the risk of PD later in life. This association was observed in both individual patient data and nationwide register data. Therefore, despite the opposite dopaminergic disease mechanisms, schizophrenia spectrum disorder increases rather than decreases the risk of PD. The increased PD risk could be related to risk-altering effects of dopamine receptor antagonists or to the increased vulnerability of the dopamine system induced by illness phase-dependent dopamine dysregulation in schizophrenia/schizophrenia spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28484DOI Listing
June 2021

A physiologically validated rat model of term birth asphyxia with seizure generation after, not during, brain hypoxia.

Epilepsia 2021 Apr 18;62(4):908-919. Epub 2020 Dec 18.

Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences, University of Helsinki, Helsinki, Finland.

Objective: Birth asphyxia (BA) is often associated with seizures that may exacerbate the ensuing hypoxic-ischemic encephalopathy. In rodent models of BA, exposure to hypoxia is used to evoke seizures, that commence already during the insult. This is in stark contrast to clinical BA, in which seizures are typically seen upon recovery. Here, we introduce a term-equivalent rat model of BA, in which seizures are triggered after exposure to asphyxia.

Methods: Postnatal day 11-12 male rat pups were exposed to steady asphyxia (15 min; air containing 5% O  + 20% CO ) or to intermittent asphyxia (30 min; three 5 + 5-min cycles of 9% and 5% O at 20% CO ). Cortical activity and electrographic seizures were recorded in freely behaving animals. Simultaneous electrode measurements of intracortical pH, Po , and local field potentials (LFPs) were made under urethane anesthesia.

Results: Both protocols decreased blood pH to <7.0 and brain pH from 7.3 to 6.7 and led to a fall in base excess by 20 mmol·L . Electrographic seizures with convulsions spanning the entire Racine scale were triggered after intermittent but not steady asphyxia. In the presence of 20% CO , brain Po was only transiently affected by 9% ambient O but fell below detection level during the steps to 5% O , and LFP activity was nearly abolished. Post-asphyxia seizures were strongly suppressed when brain pH recovery was slowed down by 5% CO .

Significance: The rate of brain pH recovery has a strong influence on post-asphyxia seizure propensity. The recurring hypoxic episodes during intermittent asphyxia promote neuronal excitability, which leads to seizures only after the suppressing effect of the hypercapnic acidosis is relieved. The present rodent model of BA is to our best knowledge the first one in which, consistent with clinical BA, behavioral and electrographic seizures are triggered after and not during the BA-mimicking insult.
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http://dx.doi.org/10.1111/epi.16790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246723PMC
April 2021
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