Purpose: The effect of acute methanol poisoning on the follow-up quality of life of survivors in mass poisoning outbreaks is not known. The objective of this is to study the impact of visual and central nervous system (CNS) sequelae of methanol poisoning on long-term health-related quality of life (QoL) of survivors, its clinical determinants, and dynamics.Materials and methods: A total of 54 patients with confirmed methanol poisoning (mean age 46.7 ± 13.4 years, 9 females) were examined consequently three times within six-year prospective cohort study and compared to 23 controls with the history of chronic alcohol abuse. The following tests were performed: SF-36 QoL questionnaire, visual evoked potentials (VEP) of optic nerve, ocular examination with retinal nerve fiber layer (RNFL) thickness measurement, brain magnetic resonance imaging (MRI), and biochemical and toxicological tests.Results: Acute methanol poisoning led to significant decrease in physical component summary (PCS) compared to PCS of age-adjusted controls (mean score with SD 46.8 ± 11.0 versus 52.3 ± 9.4 points; p = .003). In 17/40 (42.5%) patients with three rounds of examination, signs of severe disability (≤30 points in at least one score) were present six years after discharge, with negative dynamics of PCS score during the observation period. The patients with abnormal RNFL thickness had lower PCS (mean difference 10.5 points; 95%CI 3.5-17.5, p = .004) and mental component summary score (9.5 points; 95%CI 1.9-17.1, p = .015) compared to the patients with normal RNFL. Signs of physical and mental adaptation to long-term visual sequelae were registered with gradual reduction of difference in most of physical and mental components scores compared to the patients with normal RNFL during six years of observation. Signs of hemorrhagic brain lesions were associated with permanent decrease of PCS score (mean difference 7.4 points; 95%CI 0.6-14.0; p = .033), bodily pain (8.7 points; 95%CI 1.6-17.6; p = .018), and social functioning (8.2 points; 95%CI 3.0-17.4; p = .005) six years after discharge. No effect of type of antidote (fomepizole versus ethanol) and extracorporeal enhanced elimination modality (intermittent hemodialysis versus continuous renal replacement therapy) applied in hospital on long-term QoL was found (all p > .05).Conclusion: Acute methanol poisoning was associated with a significant decrease of health-related quality of life of survivors persisting for at least six years after discharge. The more pronounced decrease in QoL scores was observed in the patients with hemorrhagic brain lesions and visual sequelae of poisoning with abnormal RNFL thickness.

• MeSH
• alkoholismus komplikace   MeSH
• antidota aplikace a dávkování   MeSH
• dospělí MeSH
• epidemický výskyt choroby * MeSH
• ethanol aplikace a dávkování   MeSH
• fomepizol aplikace a dávkování   MeSH
• kohortové studie MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• methanol otrava   MeSH
• mozek diagnostické zobrazování   MeSH
• následné studie MeSH
• přežívající MeSH
• prospektivní studie MeSH
• průzkumy a dotazníky MeSH
• retina patologie   MeSH
• zrakové evokované potenciály MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

ABSTRACT: Mass methanol poisonings present a serious problem for health systems worldwide, with poor outcome associated with delayed treatment. Positive pre-hospital serum ethanol concentration may have predictive value as the prognostic factor of the treatment outcome. We studied the effect of positive serum ethanol level on admission to hospital on survival in patients treated during the Czech methanol outbreak during 2012-2014. Cross-sectional cohort study was performed in 100 hospitalized patients with confirmed methanol poisoning. Pre-hospital ethanol was administered in 42 patients (by paramedic/medical staff to 30 patients and self-administered by 12 patients before admission); 58 patients did not receive pre-hospital ethanol. Forty-two patients had detectable serum ethanol concentration on admission to hospital [median 18.3 (IQR 6.6-32.2) mmol dm-3]. Pre-hospital ethanol administration by paramedic/medical staff had a significant effect on survival without visual and CNS sequelae when adjusted for arterial blood pH on admission (OR 8.73; 95 % CI 3.57-21.34; p < 0.001). No patients receiving pre-hospital ethanol died compared with 21 not receiving (p < 0.001). Positive serum ethanol concentration on admission to hospital was a predictor for survival without health sequelae when adjusted for arterial blood pH (OR 8.10; 95 % CI 2.85-23.02; p < 0.001). The probability of visual and CNS sequelae in survivors reduced with increasing serum ethanol concentration on admission. GRAPHICAL ABSTRACT:

• MeSH
• akutní nemoc MeSH
• ethanol * terapeutické užití   MeSH
• kohortové studie MeSH
• lidé MeSH
• methanol * otrava   MeSH
• otrava mortalita   terapie   MeSH
• příjem pacientů MeSH
• průřezové studie MeSH
• sérum MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Existují určité důkazy významu environmentálních expozicí v rozvoji neurodegenerativních onemocnění. Metanol je široce používaný toxický alcohol s vysokým rizikem úmrtí a dlouhodobého poškození nervového systému. Protože není toxický pro laboratorní zvířata, klinické humanní studie jsou zapotřebí ke zvyšení našich znalostí o jeho podílu na neurodegenerativních procesech. Během České hromadné otravy methanolem v roce 2012 jsme shromaždili detailní data o 50 přeživších otravu pacientech a vyšetřili je 3-6 a 24-28 měsíců po otravě. Tento soubor pacientů nemá analogy ve světě. V době akutní otravy a za 2 roky po ni byly odebrány a zamráženy vzorky jejich krevního séra. Plánujeme sledovat character a dynamiku zjištěných neurodegenerativních změn 4-6 let po otravě v rámci pravidelných komplexních klinických vyšetření (neurologického, neuropsychologického, neurooftalmologického, biochemického, magnetické rezonance mozku, elektromyografie, zrakových evokovaných potencialů, optické koherenční tomografie) a jejich asociaci s charakterem akutního neuronálního poškození kyselinou mravenčí.; Certain evidence exists about the role of environmental exposures in neurodegenerative diseases. Methanol is widely spread toxic alcohol with high rate of mortality and nervous system damage. Because it is not toxic for lab animals, human studies are necessary to increase our knowledge about its role in neurodegenerative processes. During the Czech mass methanol outbreak in 2012, a thorough investigation and follow-up examination in 50 survivors was performed 3-6 and 24-28 months after discharge. This represents the largest and most comprehensive material ever studied worldwide. Blood serum samples were collected and frozen during the acute poisoning and after 2 years. We plan to study the character and dynamics of neurodegenerative changes 4-6 years after exposure and the associations with the character of acute neuronal damage by formic acid. The clinical protocol will include neurological/neuropsychological/neuroophthalmological and ocular examinations, magnetic resonance of brain, electromyography, visual evoked potentials, biochemical tests, retinal optical coherence tomography

• MeSH
• centrální nervový systém patologie   MeSH
• lidé MeSH
• longitudinální studie MeSH
• methanol otrava   MeSH
• neurodegenerativní nemoci etiologie   MeSH
• otrava MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• toxikologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

• MeSH
• epidemický výskyt choroby MeSH
• methanol otrava   MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• toxikologie

BACKGROUND: Methanol is a widely used industrial short-chain aliphatic alcohol with known neurotoxic properties. Mass poisoning outbreaks due to the consumption of methanol-adulterated alcoholic drinks present a challenge to healthcare providers due to the high mortality and serious central nervous system (CNS) damage in survivors. However, the impact of methanol exposure on the peripheral nervous system is unknown. OBJECTIVES: To investigate the role of acute methanol exposure in the development of peripheral polyneuropathy (PNP) during the years following discharge from the hospital. METHODS: A total of 55 patients with confirmed methanol poisoning (mean age of 47.9 ± 3.6 years; 9 females) were examined 4 times within a 6-year prospective longitudinal cohort study. The program included neurological and electromyographic examinations, visual evoked potentials, ocular examinations with retinal nerve fibre layer thickness measurements, brain magnetic resonance imaging, and a series of biochemical and toxicological tests. RESULTS: PNP was observed in 20/55 (36 %) patients, which, in most of the cases, was mild axonal sensorimotor neuropathy. In 8/55 (15 %) patients, worsening of electromyographic findings was registered during the follow-up period, including 5 cases with newly diagnosed PNP and 3 cases of PNP progression. In one subject, complete reversal of PNP was registered after cessation of alcohol intake. The patients with PNP were significantly older (57.3 ± 5.3 versus 42.5 ± 3.9 years; p < 0.001), with higher blood glucose (5.93 ± 0.97 versus 4.81 ± 0.32 mmol/L; p = 0.035) and lower vitamin B1 (45.5 ± 7.4 versus 57.5 ± 5.2 ug/L; p = 0.015) concentrations. The number of chronic alcohol abusers was significantly higher in the PNP group (17/20 versus 20/35; p = 0.034). No associations between PNP prevalence/ dynamics and acute parameters of poisoning severity, arterial blood pH (7.26 ± 0.07 with PNP versus 7.18 ± 0.09 without PNP; p = 0.150), or serum methanol (1320.0 ± 700.0 with PNP versus 1430.0 ± 510.0 mg/L without PNP; p = 0.813) and ethanol (460.0 ± 560.0 with PNP versus 340.0 ± 230.0 mg/L without PNP; p = 0.675) concentrations at admission were found. No difference in the number of patients with visual (9/20 with PNP versus 12/35 patients without PNP; p = 0.431) and CNS sequelae (9/20 with PNP versus 15/35 patients without PNP; p = 0.877) of poisoning was present. DISCUSSION: Despite the relatively high number of PNP cases, no association was found between the severity of acute methanol poisoning and the prevalence of PNP and its dynamics during six years of observation. We did not find an association between methanol-induced visual/ brain damage and the prevalence of PNP in survivors of poisoning. A high prevalence of PNP and its progression might be attributed to other causes, mainly a history of chronic alcohol abuse and insufficiently treated diabetes mellitus. Our results highlight the importance of complete cessation of alcohol consumption and better control of glycaemia in diabetic patients in the prevention and treatment of peripheral PNP.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• methanol otrava   MeSH
• nemoci periferního nervového systému chemicky indukované   diagnóza   epidemiologie   MeSH
• otrava diagnóza   epidemiologie   MeSH
• prevalence MeSH
• prognóza MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

CONTEXT: Methanol poisoning induces acute optic neuropathy with possible long-term visual damage. OBJECTIVE: To study the dynamics and key determinants of visual pathway functional changes during 4 years after acute methanol poisoning. METHODS: A total of 42 patients with confirmed methanol poisoning (mean age 45.7 ± 4.4 years) were examined 4.9 ± 0.6, 25.0 ± 0.6, and 49.9 ± 0.5 months after discharge. The following tests were performed: visual evoked potential (VEP), retinal nerve fiber layer (RNFL) measurement, brain magnetic resonance imaging (MRI), complete ocular examination, biochemical tests, and apolipoprotein E (ApoE) genotyping. RESULTS: Abnormal VEP P1 latency was registered in 18/42 right eyes (OD) and 21/42 left eyes (OS), abnormal N1P1 amplitude in 10/42 OD and OS. Mean P1 latency shortening during the follow-up was 15.0 ± 2.0 ms for 36/42 (86%) OD and 14.9 ± 2.4 ms for 35/42 (83%) OS, with maximum shortening up to 35.0 ms. No significant change of mean N1P1 amplitude was registered during follow-up. A further decrease in N1P1 amplitude ≥1.0 mcV in at least one eye was observed in 17 of 36 patients (47%) with measurable amplitude (mean decrease -1.11 ± 0.83 (OD)/-2.37 ± 0.66 (OS) mcV versus -0.06 ± 0.56 (OD)/-0.83 ± 0.64 (OS) mcV in the study population; both p < .001). ApoE4 allele carriers had lower global and temporal RNFL thickness and longer initial P1 latency compared to the non-carriers (all p < .05). The odds ratio for abnormal visual function was 8.92 (3.00-36.50; 95%CI) for ApoE4 allele carriers (p < .001). The presence of ApoE4 allele was further associated with brain necrotic lesions (r = 0.384; p = .013) and brain hemorrhages (r = 0.395; p = .011). CONCLUSIONS: Improvement of optic nerve conductivity occurred in more than 80% of patients, but evoked potential amplitude tended to decrease during the 4 years of observation. ApoE4 allele carriers demonstrated lower RNFL thickness, longer P1 latency, and more frequent methanol-induced brain damage compared to non-carriers.

• MeSH
• apolipoprotein E4 genetika   MeSH
• časové faktory MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• methanol otrava   MeSH
• následné studie MeSH
• nemoci zrakového nervu chemicky indukované   diagnóza   genetika   patofyziologie   MeSH
• nervus opticus účinky léků   patofyziologie   MeSH
• poruchy zraku chemicky indukované   diagnóza   genetika   patofyziologie   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• reakční čas MeSH
• rizikové faktory MeSH
• studie případů a kontrol MeSH
• zrak účinky léků   genetika   MeSH
• zrakové evokované potenciály MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

As the susceptibility of humans to xenobiotics often depends on genetic factors, we assumed that ADH1B and ALDH2 genetic variants may affect susceptibility to the acute methanol exposure. To evaluate the role of genetic variants of enzymes involved in methanol catabolism in humans, we analysed ADH1B (rs1229984) and ALDH2 (rs441) polymorphisms in 50 adults who survived acute methanol poisoning, 246 individuals with alcoholic liver cirrhosis, and in 545 healthy controls. GG homozygotes of ADH1B were more common among methanol-poisoned patients (98%) and among patients with alcoholic liver cirrhosis (98%) than among healthy controls (90%) (P = 0.08 and < 0.001, respectively). Minor C allele carriers of the ALDH2 were significantly more common among methanol-poisoned persons (46%) than among patients with alcoholic liver cirrhosis or healthy controls (31% in both groups, P < 0.05 and 0.025, respectively); the odds ratios were 1.89 (95% CI 1.02-3.52) and 1.94 (1.08-3.48), respectively. As there was a substantial amount of subjects with alcohol abuse between both groups of patients, ADH1B is unlikely to affect the susceptibility to methanol poisoning. By contrast, the genetic variant of the ALDH2 enzyme seems to specifically affect the susceptibility to methanol in acutely exposed humans and potentially plays a role in the outcome of methanol poisoning.

• MeSH
• alely MeSH
• alkoholismus komplikace   etiologie   MeSH
• dospělí MeSH
• farmakogenomické varianty * MeSH
• genotyp MeSH
• jaterní cirhóza etiologie   patologie   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• methanol škodlivé účinky   otrava   MeSH
• mitochondriální aldehyddehydrogenasa genetika   MeSH
• mladý dospělý MeSH
• odds ratio MeSH
• polymorfismus genetický * MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Intermittent hemodialysis (IHD) is the modality of choice in the extracorporeal treatment (ECTR) of acute methanol poisoning. However, the comparative clinical effectiveness of intermittent versus continuous modalities (CRRT) is unknown. During an outbreak of mass methanol poisoning, we therefore studied the effect of IHD versus CRRT on mortality and the prevalence of visual/central nervous system (CNS) sequelae in survivors. METHODS: The study was designed as prospective observational cohort study. Patients hospitalized with a diagnosis of acute methanol poisoning were identified for the study. Exploratory factor analysis and multivariate logistic regression were applied to determine the effect of ECTR modality on the outcome. RESULTS: Data were obtained from 41 patients treated with IHD and 40 patients with CRRT. The follow-up time in survivors was two years. Both groups of patients were comparable by age, time to presentation, laboratory data, clinical features, and other treatment applied. The CRRT group was more acidemic (arterial blood pH 6.96 ± 0.08 vs. 7.17 ± 0.07; p < 0.001) and more severely poisoned (25/40 vs. 9/41 patients with Glasgow Coma Scale (GCS) ≤ 8; p < 0.001). The median intensive care unit length of stay (4 (range 1-16) days vs. 4 (1-22) days; p = 0.703) and the number of patients with complications during the treatment (11/41 vs. 13/40 patients; p = 0.576) did not differ between the groups. The mortality was higher in the CRRT group (15/40 vs. 5/41; p = 0.008). The number of survivors without sequelae of poisoning was higher in the IHD group (23/41 vs. 10/40; p = 0.004). There was a significant association of ECTR modality with both mortality and the number of survivors with visual and CNS sequelae of poisoning, but this association was not present after adjustment for arterial blood pH and GCS on admission (all p > 0.05). CONCLUSIONS: In spite of the faster correction of the acidosis and the quicker removal of the toxic metabolite in intermittent dialysis, we did not find significant differences in the treatment outcomes between the two groups after adjusting for the degree of acidemia and the severity of poisoning on admission. These findings support the strategy of "use what you have" in situations with large outbreaks and limited dialysis capacity.

• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

OBJECTIVES: The study focuses on the 2012 methanol outbreak in the Czech Republic. The main goal of the present study was to apply analytical and descriptive tools to selected qualitative and quantitative processes related to the 2012 methanol outbreak in the Czech Republic. The secondary goal was to study and evaluate in detail their potential for creating integrated conceptual national policies aimed at eliminating the risk of methanol poisoning in the future. METHODS: The presented qualitative analysis focused on the content of documents published by Czech public authorities - the Ministry of Health, the Ministry of the Interior, the Czech Agriculture and Food Inspection Authority, and the Regional Public Health Authorities - as well as the content of the relevant legal regulations. Moreover, statistical data concerning the number of hospitalisations and deaths due to the methanol intoxication were used to provide a background to a detailed description of the relevant facts. RESULTS: In procedural terms, most of the analysed measures focused on a strongly restrictive regulation of sales, regular information channels designed to protect consumers on the national as well as international level, and elimination of further health and economic risks stemming from the dangerous alcoholic products that had already entered distribution networks. The health, social and economic consequences of such activities are quantified at a highly aggregated level. The analysed institutional ties are evaluated also in the context of international documents: the European Action Plan to Reduce Harmful Use of Alcohol 2012-2020 and the Global Strategy to Reduce Harmful Use of Alcohol, and their current potential for steering public policies is assessed. CONCLUSION: The analysis and evaluation of procedural activities carried out after the methanol outbreak have laid the foundations for a multidimensional study that can contribute to integrated national policy concepts aimed at preventing these and similar negative health, societal and economic consequences. Six years after the methanol outbreak, national and regional health policies have reflected no findings concerning the experience of patients whose health was impaired due to methanol, and the economic cost of the event has not been calculated. The quality of life of these patients has greatly decreased due to permanent or partial incapacity and serious upheavals of their and their families' economic and social conditions. This opens the question of researching and evaluating multiple aspects of health, social and economic impacts of harmful use of alcohol and setting up processes to mitigate these impacts.

• MeSH
• epidemický výskyt choroby * MeSH
• kvalitativní výzkum MeSH
• lidé MeSH
• methanol otrava   MeSH
• otrava epidemiologie   MeSH
• veřejná politika * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH