Papers by Mailis Tõnisson
study of forensic autopsies using novel biomarkers and proxy informants

Aims: To describe clinical, mental and physical signs in children with different severity acute a... more Aims: To describe clinical, mental and physical signs in children with different severity acute alcohol intoxication (AAI) determined either by serum alcohol concentration (SAC) or by blood alcohol concentration (BAC) to study the diagnostic performance characteristics of clinical assessment and to establish the ratio of SAC:BAC in children. Methods: Data were analysed from 256 children aged 8.4-17.9 years who were hospitalized at Estonia's two children's hospitals over a 3-year period. In each case, the on-call paediatri- cian completed a special form about the clinical, mental (consciousness, balance and speech) and physical (muscle tone, blood pressure, pulse and body temperature) signs of AAI. Blood samples were drawn for measurements of SAC and BAC. Diagnostic performance characteristics (sensitivity, specificity, efficiency) of the clinical assessments and the SAC:BAC ratio were calculated. Results: The most correctly described signs in children in different SAC groups...
The prevalence of biochemical (glucose, lactate, potassium and sodium) changes in serum in childr... more The prevalence of biochemical (glucose, lactate, potassium and sodium) changes in serum in children with AAI, and the impact of SAC on the biochemical changes in serum ..

65aastane naine leiti kodust surnuna, eelmisel paeval oli leitud samast tema abikaasa – 62aastane... more 65aastane naine leiti kodust surnuna, eelmisel paeval oli leitud samast tema abikaasa – 62aastane mees. Molema surnukeha kohtuarstlikul lahangul jai kahtlus raskmetallimurgistuse suhtes. Vere analuusides leiti molema lahkunu vereproovis toksilistes vaartustes seleenisisaldus, mis oli otsene surmapohjus. Lahanguleid oli mehel ja naisel sarnane: suu limaskestal oranžikaspunane olijas aine, sarnane aine maos ja kaksteistsormikus, siseelundite oranžikas varvus ning dehudreerunud valimus. Kohtuarstlikul lahangul sedastati lisaks veel mehel maksatsirroos ja hepatiit, alkoholi kontsentratsioon veres oli 1,56 mg/g (‰). Paev hiljem surnud naisel esines rasvmaks ja steatohepatiit, alkoholi kontsentratsioon veres oli 0,34 mg/g (‰). Kirjanduse andmetel esineb inimestel agedat seleenimurgistust aarmiselt harva ja teadaolevalt pole seda varem Eestis diagnoositud. Ageda seleenimurgistuse korral voivad esineda tugev kohuvalu, profuusne diarroa ja oksendamine ning kuuslaugu lohn suust. Eesti Arst 20...

Forensic Sciences Research, 2018
The study was conducted at the Estonian Forensic Science Institute in 2008-2014 as continuous par... more The study was conducted at the Estonian Forensic Science Institute in 2008-2014 as continuous part of our previous study of alcohol and premature death in Estonian men. Autopsy data from 504 cases of male deaths (ages 19-79) were collected and blood and urine samples for glycated haemoglobin (HbA 1c), liver enzymes and alcohol concentration were analysed. The aim of our research was to find undiagnosed diabetes and diabetes risk cases postmortem on the basis of increased values of HbA 1c. HbA 1c was within the reference value 4.8%-5.9% (29-42 mmol/mol), in 88.1% (n = 444) of cases, below reference value in 2.4% (n = 12), in the risk group of diabetes, HbA 1c 6.0%-6.4% (42-46 mmol/mol) was within 5.8% (n = 29), and HbA 1c result of 6.5% (48 mmol/mol) manifested in 3.8% (n = 19) of cases. The higher the age, the more cases with HbA 1c value 6.0% (42 mmol/mol) occurred. In the group of external causes of death (n = 348), the HbA 1c value of 6.5% (48 mmol/mol) HbA 1c occurred in four cases. The HbA 1c value was 6.5% (48 mmol/mol) in 78.9% of 156 cases when the cause of death was disease, of which 58% were cardiovascular diseases. The prevalence of diabetes and diabetes risk was found lower compared to population-based study, as majority of the deceased were young and middle-aged males and no females were included. In the case of poisoning with narcotic substances, HbA 1c was within the reference range. A negative correlation occurred between alcohol intoxication and HbA 1c value. A positive correlation between ALT and HbA 1c was foundthe higher stage of liver damage correlated with the higher HbA 1c level.

Romanian Journal of Legal Medicine, 2012
Background: Official mortality registers are of fundamental importance in research, however the c... more Background: Official mortality registers are of fundamental importance in research, however the comparability of data across countries and different versions of ICD (International Classification of Diseases) must be monitored. The aim of this article is to examine the impact of ICD coding rules, as there were three major updates between 2002 and 2010 affecting fatal poisoning data. Method: Data on all fatal poisonings registered by the Estonian Forensic Science Institute from 2000-2009 were coded according to ICD (effective in 2010), correspondence between forensic diagnosis and ICD categories and the impact of changes on ICD examined. Results: Priority lists to select the main substance in the case of multi-substance poisoning do not always result in the most dangerous drug. In particular, highly toxic fentanyles are rated below psychostimulants, which leads (in the case of Estonia) to significant distortion of drug-related mortality patterns. Implementation of the updates to ICD coding rules stating that aspiration may be due to other conditions results in a 16.8% increase in drug-related mortality. Tranquillizers such as benzodiazepines and barbiturates are absent from this list altogether. There are no guidelines to deal with surrogate alcohol. Conclusion: Implementation of the 2010 version of ICD must be carefully monitored by statistical authorities and researchers. The priority list for substances could be amended to give priority to fentanyles over psychostimulants and to frequently abused tranquillizers (benzodiazepines and barbiturates) over non-opioid analgesics. Certain combinations of toxic agents could have separate codes in ICD, especially if they have a coalitive effect.

Addiction (Abingdon, England), 2014
Alcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-... more Alcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-related deaths are classified according to a single underlying cause. We sought to quantify this issue and its implications for analysing mortality data. Cross-sectional study included 554 men aged 25-54 in Estonia undergoing forensic autopsy in 2008-09. Potentially alcohol-related pathologies were identified following macroscopic and histological examination. Alcohol biomarkers levels were determined. For a subset (26%), drinking behaviour was provided by next-of-kin. The Estonian Statistics Office provided underlying cause of death. Most deaths (75%) showed evidence of potentially alcohol-related pathologies, and 32% had pathologies in two or more organs. The liver was most commonly affected [60.5%, 95% confidence interval (CI) = 56.3-64.6] followed by the lungs (18.6%, 95% CI = 15.4-22.1), stomach (17.5%, 95% CI = 14.4-20.9), pancreas (14.1%, 95% CI = 11.3-17.3), heart (4.9%, 95% CI =...
Alcohol, 2010
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Etanool on kõige enam kuritarvitatud... more Väitekirja elektrooniline versioon ei sisalda publikatsioone.Etanool on kõige enam kuritarvitatud aine nii Lääneriikides, kui ka Eestis. Rohke alkoholi tarvitamisega kaasnevad alkoholist tingitud probleemid ka lastel ja noorukitel. Igapäevase haiglatöö seisukohast oli eesmärgiks uurida alkoholijoobes lastel esinevaid kliinilisi tunnuseid erinevatel joobe raskusastmetel ning kliinilise leiu korrelatsiooni seerumi alkoholi kontsentratsiooniga (SAC), juriidilisest aspektist oli oluline tuvastada seerumi ja vere alkoholi kontsentratsioonide suhe. Samuti oli uuringu eesmärkideks oli teha kindlaks ägeda alkoholi intoksikatsiooniga lastel elutähtsate analüütide (glükoos - Glu, laktaat - Lak, kaalium - K, naatrium - Na) muutuste esinemine ning muutuste seos alkoholi kontsentratsiooniga või hormonaalse (testosteroon, östradiool, progesteroon, kortisool) hetkeseisuga. Uuringus osalesid 3 aasta jooksul (2005-2008) Tartu Ülikooli Lastekliinikusse või Tallinna Lastehaiglasse hospitaliseeritud al...

Forensic Sciences Research
The study was conducted at the Estonian Forensic Science Institute in 2008-2014 as continuous par... more The study was conducted at the Estonian Forensic Science Institute in 2008-2014 as continuous part of our previous study of alcohol and premature death in Estonian men. Autopsy data from 504 cases of male deaths (ages 19-79) were collected and blood and urine samples for glycated haemoglobin (HbA 1c), liver enzymes and alcohol concentration were analysed. The aim of our research was to find undiagnosed diabetes and diabetes risk cases postmortem on the basis of increased values of HbA 1c. HbA 1c was within the reference value 4.8%-5.9% (29-42 mmol/mol), in 88.1% (n = 444) of cases, below reference value in 2.4% (n = 12), in the risk group of diabetes, HbA 1c 6.0%-6.4% (42-46 mmol/mol) was within 5.8% (n = 29), and HbA 1c result of 6.5% (48 mmol/mol) manifested in 3.8% (n = 19) of cases. The higher the age, the more cases with HbA 1c value 6.0% (42 mmol/mol) occurred. In the group of external causes of death (n = 348), the HbA 1c value of 6.5% (48 mmol/mol) HbA 1c occurred in four cases. The HbA 1c value was 6.5% (48 mmol/mol) in 78.9% of 156 cases when the cause of death was disease, of which 58% were cardiovascular diseases. The prevalence of diabetes and diabetes risk was found lower compared to population-based study, as majority of the deceased were young and middle-aged males and no females were included. In the case of poisoning with narcotic substances, HbA 1c was within the reference range. A negative correlation occurred between alcohol intoxication and HbA 1c value. A positive correlation between ALT and HbA 1c was foundthe higher stage of liver damage correlated with the higher HbA 1c level.
Journal of Addiction Research & Therapy, 2011

Addiction (Abingdon, England), 2014
Alcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-... more Alcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-related deaths are classified according to a single underlying cause. We sought to quantify this issue and its implications for analysing mortality data. Cross-sectional study included 554 men aged 25-54 in Estonia undergoing forensic autopsy in 2008-09. Potentially alcohol-related pathologies were identified following macroscopic and histological examination. Alcohol biomarkers levels were determined. For a subset (26%), drinking behaviour was provided by next-of-kin. The Estonian Statistics Office provided underlying cause of death. Most deaths (75%) showed evidence of potentially alcohol-related pathologies, and 32% had pathologies in two or more organs. The liver was most commonly affected [60.5%, 95% confidence interval (CI) = 56.3-64.6] followed by the lungs (18.6%, 95% CI = 15.4-22.1), stomach (17.5%, 95% CI = 14.4-20.9), pancreas (14.1%, 95% CI = 11.3-17.3), heart (4.9%, 95% CI =...

Journal of Forensic and Legal Medicine, 2013
The aim of this study is to provide an overview of deaths caused by poisoning (especially illicit... more The aim of this study is to provide an overview of deaths caused by poisoning (especially illicit drugs) in Estonia from 2000 to 2009. The data on poisoning deaths (N = 4132) were collected from the autopsy reports of the Estonian Forensic Science Institute. Ethanol poisoning was the most frequent cause of death (N = 1449, 35.1%), followed by carbon monoxide (N = 1151, 27.9%) and poisoning from illicit drugs (N = 888, 21.5%). The study included 3267 male (79.1%) and 865 female fatalities, with the prevalent age group being 35-64 years. Since 2002, deaths from fentanyles have increased sharply and remained at a high level - from 63 cases in 2002 to 138 cases in 2009. This high number indicates that in spite of the state's drug policies, illegal drugs remain easily available and that this area requires more attention. Alcohol abuse prevention policies - restrictions on alcohol advertisements in the media, limitations on sale times and anti-alcohol campaigns concerning traffic - have not brought about a significant decrease in ethanol poisoning.
BMC Public Health, 2012
Background: Alcohol makes an important contribution to premature mortality in many countries in E... more Background: Alcohol makes an important contribution to premature mortality in many countries in Eastern Europe, including Estonia. However, the full extent of its impact, and the mechanisms underlying it, are challenging issues to research. We describe the design and initial findings of a study aimed at investigating the association of alcohol with mortality in a large series of forensic autopsies of working-age men in Estonia. Methods: 1299 male deaths aged 25-54 years were subject to forensic autopsy in 2008-2009. The routine autopsy protocol was augmented by a more systematic inspection of organs, drug testing, assay of liver enzymes and novel biomarkers of alcohol consumption (EtG, EtS and PEth), together with proxy interviews with next of kin for deaths among men who lived in or close to a major town.

Alcohol and Alcoholism, 2013
Aims: To describe clinical, mental and physical signs in children with different severity acute a... more Aims: To describe clinical, mental and physical signs in children with different severity acute alcohol intoxication (AAI) determined either by serum alcohol concentration (SAC) or by blood alcohol concentration (BAC) to study the diagnostic performance characteristics of clinical assessment and to establish the ratio of SAC:BAC in children. Methods: Data were analysed from 256 children aged 8.4-17.9 years who were hospitalized at Estonia's two children's hospitals over a 3-year period. In each case, the on-call paediatrician completed a special form about the clinical, mental (consciousness, balance and speech) and physical (muscle tone, blood pressure, pulse and body temperature) signs of AAI. Blood samples were drawn for measurements of SAC and BAC. Diagnostic performance characteristics (sensitivity, specificity, efficiency) of the clinical assessments and the SAC:BAC ratio were calculated. Results: The most correctly described signs in children in different SAC groups were consciousness (r s = 0.16) and speech (r s = 0.13) (P < 0.0001). The severity of alteration of consciousness and degrees of disturbance in balance and speech were positively correlated with SAC (P < 0.001). The clinical judgment matched better with AAI determined by SAC rather than by BAC with the mean efficiency. The mean ratio between SAC and BAC was 1.19 ± 0.13 (P < 0.001) in children. Conclusion: The level of consciousness is the leading sign in the clinical evaluation of children with AAI and correlates well with SAC. The severity of AAI judged by clinical assessment matched better with AAI severity stages determined by SAC than by BAC. For legal cases where BAC is required, the SAC:BAC ratio of 1.19:1 should be used in children regardless of their gender or age.

Alcohol, 2010
The aim of our research was to study prevalence of changes in plasma levels of lactate, potassium... more The aim of our research was to study prevalence of changes in plasma levels of lactate, potassium, glucose, and sodium in relation to alcohol concentration in children hospitalized with acute alcohol intoxication (AAI). Data from 194 under 18-year-old children hospitalized to the two only children's hospital in Estonia over a 2-year period were analyzed. The pediatrician on call filled in a special form on the clinical symptoms of AAI; a blood sample was drawn for biochemical tests, and a urine sample taken to exclude narcotic intoxication. The most common finding was hyperlactinemia occurring in 66% of the patients (n 5 128) followed by hypokalemia (!3.5 mmol/L) in 50% (n 5 97), and glucose above of reference value (O6.1 mmol/L) in 40.2% of the children (n 5 78). Hypernatremia was present in five children. In conclusion, hyperlactinemia, hypokalemia, and glucose levels above of reference value are common biochemical findings in children hospitalized with acute AAI. Ó
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Papers by Mailis Tõnisson