Fatal cases of hemorrhagic fever with renal syndrome in Udmurtia, Russia, 2010 to 2019.

Hemorrhagic fever with renal syndrome (HFRS) continues to be a cause of death in Europe. Our aim was to describe the clinical and histopathological features of fatal HFRS in the Udmurt Republic (Udmurtia), located in the European part of Russia. This retrospective observational study included all fatal cases of HFRS that occurred in Udmurtia from January 2010 through December 2019. The most relevant clinical and autopsy data of these cases were recorded through a review of the patients' medical records and autopsy reports. During 2010-2019, Udmurtia had 41 fatal cases of HFRS of a total of 10,312 confirmed cases (case-fatality rate of 0.4%). Twenty-seven patients died in hypotensive and oliguric phases of HFRS due to refractory septic shock and acute respiratory distress syndrome. Fourteen patients died in the polyuric phase of the disease from complications of acute kidney injury or because of hospital-acquired bacterial infections. Multiorgan involvement was noted in all autopsies with variable degrees of generalized venous congestion, interstitial edema, capillary wall thickening, perivascular deposition of plasma proteins, microthrombosis formation, and perivascular hemorrhage. The more prominent histopathological features were seen in kidneys, lungs, and hypophysis.

Pathologic morphology of acute experimental osteomyelitis.

The goal of our work was to study the changes in the bone tissue, bone marrow and surrounding tissues in animals during early stages of experimental osteomyelitis. Osteomyelitis was simulated in 30 infants rabbits aged 3-4 months whose body weight accounted 1200-1600 grams through the insertion of 5-6 million of aurococcus into the marrow channel of a shinbone. The study of bone marrow, bone tissue and surrounding tissue was conducted 30 minutes, 6, 12, 24, 48 and 60 hours after the contamination with the help of light and electronic (transmission and scanning) microscopy. It was proved that the first changes are characterized by the evident changes in the vessel's walls which cause the swelling of bone marrow and suppurative inflammation in the bone tissue occurs only in the end of the 3d day of the experiment. These data confirm the necessity of osteoperfortation during the first 24 hours of contamination in order to remove the swelling and to correct vessel disorders.

Comparative performance of biomarkers of alcohol consumption in a population sample of working-aged men in Russia: the Izhevsk Family Study.

AIMS: To assess the performance of a range of biomarkers of alcohol consumption in a heavy-drinking population of working-aged Russian men. DESIGN: Cross-sectional study of men originally sampled at random from a population register. SETTING: Izhevsk, a Russian city with a population of 650 000 people. PARTICIPANTS: A total of 1023 men aged 27-59 years living in Izhevsk who took part in a health check examination in 2008-2009. MEASUREMENTS: Self-reported alcohol consumption, hazardous drinking behaviours, socio-economic position, anthropometric measurements plus blood levels of alcohol biomarkers [carbohydrate-deficient transferrin (CDT, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and mean cell volume of erythrocytes (MCV)] and hepatitis B and C status. FINDINGS: In the year before interview there was a high prevalence of high-risk alcohol consumption indicated by consumption of non-beverage alcohols (5%), problem drinking behaviours (4.4%) and alcohol consumption exceeding an average 40 g per day (12.6%). All biomarkers were associated strongly with total beverage alcohol consumption even after adjustment for confounders. CDT performed best as an alcohol biomarker, with a sensitivity of 67% and specificity of 71% for detecting an average consumption of more than 40 g per day versus less. For all biomarkers sensitivity was considerably lower than specificity. Hazardous drinking patterns per se were not well detected by any of the biomarkers, all with sensitivity below 60%. CONCLUSIONS: In a Russian population with high levels of alcohol consumption, carbohydrate-deficient transferrin (CDT) might be the most sensitive and specific biomarker for detecting ethanol consumption above 40 g/day. A biomarker reflecting hazardous drinking patterns has yet to be established.

Alcohol-related dysfunction in working-age men in Izhevsk, Russia: an application of structural equation models to study the association with education.

BACKGROUND: Acute alcohol-related dysfunctional behaviours, such as hangover, are predictive of poor health and mortality. Although much is known about the association of education with alcohol consumption, little is known about its association with these dysfunctional behaviours. METHODS: The study population was 1,705 male drinkers aged 25-54 years resident in the city of Izhevsk, Russia who participated in a cross-sectional survey (2003-6). Structural equation modelling was used to examine the relationships between education, beverage and non-beverage alcohol intake, drinking patterns, and acute alcohol-related dysfunction score among these drinkers. RESULTS: Dysfunction was related to all other drinking variables, with the strongest predictors being spirit intake, non-beverage alcohol consumption and drinking patterns. There was a strong relationship between education and acute dysfunction which was not explained by adjusting for alcohol intake and drinking patterns (mean adjusted dysfunction score 0.35 SD (95% CI 0.10, 0.61) lower in men with higher versus secondary education). CONCLUSIONS: Although by definition one or more aspects of alcohol consumption should explain the educational differences in alcohol-related dysfunction, detailed information on drinking only partly accounted for the observed patterns. Thus beyond their intrinsic interest, these results illustrate the challenges in constructing statistical models that convincingly identify the pathways that link educational differences to health-related outcomes.

Hazardous alcohol consumption is associated with increased levels of B-type natriuretic peptide: evidence from two population-based studies.

Russia has very high mortality from cardiovascular disease (CVD), with evidence that heavy drinking may play a role. To throw further light on this association we have studied the association of alcohol with predictors of CVD risk including B-type natriuretic peptide (BNP). Levels of BNP increase primarily in response to abnormal cardiac chamber wall stretch which can occur both as a result of atherosclerosis as well as due to other types of damage to the myocardium. No previous population-based studies have investigated the association with alcohol. We analysed cross-sectional data on drinking behaviour in 993 men aged 25-60 years from the Izhevsk Family Study 2 (IFS2), conducted in the Russian city of Izhevsk in 2008-2009. Relative to non-drinkers, men who drank hazardously had an odds ratio (OR) of being in the top 20 % of the BNP distribution of 4.66 (95 % CI 2.13, 10.19) adjusted for age, obesity, waist-hip ratio, and smoking. Further adjustment for class of hypertension resulted in only slight attenuation of the effect, suggesting that this effect was not secondary to the influence of alcohol on blood pressure. In contrast hazardous drinking was associated with markedly raised ApoA1 and HDL cholesterol levels, but had little impact on levels of ApoB and LDL cholesterol. Similar but less pronounced associations were found in the Belfast (UK) component of the PRIME study conducted in 1991. These findings suggest that the association of heavy drinking with increased risk of cardiovascular disease may be partly due to alcohol-induced non-atherosclerotic damage to the myocardium.

Hazardous alcohol consumption is a major factor in male premature mortality in a typical Russian city: prospective cohort study 2003-2009.

INTRODUCTION: Russia has experienced massive fluctuations in mortality at working ages over the past three decades. Routine data analyses suggest that these are largely driven by fluctuations in heavy alcohol drinking. However, individual-level evidence supporting alcohol having a major role in Russian mortality comes from only two case-control studies, which could be subject to serious biases due to their design. METHODS AND FINDINGS: A prospective study of mortality (2003-9) of 2000 men aged 25-54 years at recruitment was conducted in the city of Izhevsk, Russia. This cohort was free from key limitations inherent in the design of the two earlier case-control studies. Cox proportional hazards regression was used to estimate hazard ratios of all-cause mortality by alcohol drinking type as reported by a proxy informant. Hazardous drinkers were defined as those who either drank non-beverage alcohols or were reported to regularly have hangovers or other behaviours related to heavy drinking episodes. Over the follow-up period 113 men died. Compared to non-hazardous drinkers and abstainers, men who drank hazardously had appreciably higher mortality (HR = 3.4, 95% CI 2.2, 5.1) adjusted for age, smoking and education. The population attributable risk percent (PAR%) for hazardous drinking was 26% (95% CI 14,37). However, larger effects were seen in the first two years of follow-up, with a HR of 4.6 (2.5, 8.2) and a corresponding PAR% of 37% (17, 51). INTERPRETATION: This prospective cohort study strengthens the evidence that hazardous alcohol consumption has been a major determinant of mortality among working age men in a typical Russian city. As such the similar findings of the previous case-control studies cannot be explained as artefacts of limitations of their design. As Russia struggles to raise life expectancy, which even in 2009 was only 62 years among men, control of hazardous drinking must remain a top public health priority.

The efficacy of a brief intervention in reducing hazardous drinking in working age men in Russia: the HIM (Health for Izhevsk men) individually randomised parallel group exploratory trial.

BACKGROUND: Russia has particularly low life expectancy for an industrialised country, with mortality at working ages having fluctuated dramatically over the past few decades, particularly among men. Alcohol has been identified as the most likely cause of these temporal variations. One approach to reducing the alcohol problem in Russia is 'brief interventions' which seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behaviour change. Very few studies to evaluate the efficacy of brief interventions in Russia have been conducted. Motivational Interviewing (MI) is a person-centred counselling style which can be adapted to brief interventions in which help is offered in thinking through behaviour in the context of values and goals, to decide whether change is needed, and if so, how it may best be achieved. METHODS: This paper reports on an individually randomised two-armed parallel group exploratory trial. The primary hypothesis is that a brief adaptation of MI will be effective in reducing self-reported hazardous and harmful drinking at 3 months. Participants were drawn from the Izhevsk Family Study II, with eligibility determined based on proxy reports of hazardous and harmful drinking in the past year. All participants underwent a health check, with MI subsequently delivered to those in the intervention arm. Signed consent was obtained from those in the intervention arm only at this point. Both groups were then invited for 3 and 12 month follow ups. The control group did not receive any additional intervention. RESULTS: 441 men were randomised. Of these 61 did not have a health check leaving 190 in each trial arm. Follow up at 3 months was high (97% of those having a health check), and very similar in the two trial arms (183 in the intervention and 187 in the control). No significant differences were detected between the randomised groups in either the primary or the secondary outcomes at three months in the intention to treat analyses. The unadjusted odds ratio (95% CI) for the effect of MI on hazardous and harmful drinking was 0.77 (0.51, 1.16). An adjusted odds ratio of 0.52 (0.28, 0.94) was obtained in the pre-specified per protocol analysis. CONCLUSIONS: This trial demonstrates that it is possible to engage Russian men who drink hazardously in a brief intervention aimed at reducing alcohol related harm. However the results with respect to the efficacy are equivocal and further, larger-scale trials are warranted. TRIAL REGISTRATION: ISRCTN: ISRCTN82405938.

Socio-demographic predictors of dimensions of the AUDIT score in a population sample of working-age men in Izhevsk, Russia.

AIMS: To investigate the relationship between socio-demographic factors and alcohol drinking patterns identified through a formal analysis of the factor structure of the Alcohol Use Disorders Identification Test (AUDIT) score in a population sample of working-age men in Russia. METHODS: In 2008-2009, a sample of 1005 men aged 25-59 years living in Izhevsk, Russia were interviewed and information collected about socio-demographic circumstances. Responses to the AUDIT questions were obtained through a self-completed questionnaire. Latent dimensions of the AUDIT score were determined using confirmatory factor analysis and expressed as standard deviation (SD) units. Structural equation modelling was used to estimate the strength of association of these dimensions with socio-demographic variables. RESULTS: The AUDIT was found to have a two-factor structure: alcohol consumption and alcohol-related problems. Both dimensions were higher in men who were unemployed seeking work compared with those in regular paid employment. For consumption, there was a difference of 0.59 SDs, (95% confidence interval (CI): 0.23, 0.88) and for alcohol-related problems one of 0.66 SD (95% CI: 0.31, 1.00). Alcohol-related problems were greater among less educated compared with more educated men (P-value for trend = 0.05), while consumption was not related to education. Similar results were found for associations with an amenity index based on car ownership and central heating. Neither dimension was associated with marital status. While we found evidence that the consumption component of AUDIT was underestimated, this did not appear to explain the associations of this dimension with socio-demographic factors. CONCLUSIONS: Education and amenity index, both measures of socio-economic position, were inversely associated with alcohol-related problems but not with consumption. This discordance suggests that self-reported questions on frequency and volume may be less sensitive markers of socio-economic variation in drinking than are questions about dependence and harm. Further investigation of the validity of the consumption component of AUDIT in Russia is warranted as it appears that the concept of a standard 'drink' as used in the instrument is not understood.

Alcohol increases circulatory disease mortality in Russia: acute and chronic effects or misattribution of cause?

BACKGROUND: There is a consensus that the large fluctuations in mortality seen in Russia in the past two decades can be attributed to trends in alcohol consumption. However, the precise mechanisms linking alcohol to mortality from circulatory disease remain unclear. It has recently been argued that a substantial number of such deaths currently ascribed to cardiovascular disorders are misclassified cases of acute alcohol poisoning. METHODS: Analysis of routine mortality data and of a case-control study of mortality among working-age (25-54 years) men occurring in the Russian city of Izhevsk, west of the Ural mountains, 2003-05. Interviews were carried out with proxy informants for both the dead cases (N = 1750) and the controls (N = 1750) selected at random from a population register. Mortality was analysed according to indicators of alcohol problems. RESULTS: Hazardous drinking was associated with an increased risk of death from circulatory diseases as a whole [odds ratio (OR) = 4.14, 95% confidence interval (CI) 3.23, 5.31] adjusted for age, smoking and education. The association with alcoholic cardiomyopathy was particularly strong (OR = 15.7, 95% CI 9.5, 25.9). Although there was no association with deaths from myocardial infarction (MI; OR = 1.17, 95% CI 0.59, 2.32), there was a strong association with the aggregate of all other ischaemic heart disease (IHD; OR = 4.04, 95% CI 2.79, 5.84). Stronger associations for each of these causes (other than MI) were seen with whether or not the man had drunk very heavily in the previous week. However, associations also remained when analyses were restricted to subjects with no evidence of recent heavy drinking, suggesting that misclassification of acute alcohol poisonings is unlikely to explain these overall associations. CONCLUSION: Taken as a whole, the available evidence suggests that the positive association of alcohol with increased cardiovascular disease mortality may be best explained as being the result of a combination of chronic and acute alcohol consumption resulting in alcohol-related cardiac disorders, especially cardiomyopathy, rather than being due to misclassification of acute alcohol poisoning. Further work is required to understand the mechanisms underlying the link between heavy alcohol consumption and deaths classified as being due to IHD (other than MI).

A case-control analysis of socio-economic and marital status differentials in alcohol- and non-alcohol-related mortality among working-age Russian males.

BACKGROUND: We examined the role of socio-economic status (SES) and marital status in premature mortality among working-age Russian males. Life expectancy among this group dropped sharply following the collapse of the Soviet Union and has yet to recover despite the relative economic and political stability of the last decade. METHODS: We employed individual-level data from a large-scale, population-based, case-control study (n = 3500). Adjusting for age group, hazardous drinking and smoking status, we estimated mortality odds ratios to determine the impact of SES and marital status on premature mortality due to all, alcohol- and non-alcohol-related causes of death. RESULTS: Results revealed clear protective effects of SES and marital status against premature mortality. Although the effects for marital status were significant across alcohol- and non-alcohol-related causes of death, the effects of SES were largely limited to non-alcohol-related causes of death. When heavy drinkers were excluded from the analysis, however, SES was found to protect against premature mortality for alcohol-related causes. CONCLUSION: While hazardous drinking is known to be a leading cause of premature mortality among working-age Russian males, it is unwise to ignore other factors. Given the substantial social and economic impacts in Russia of the dissolution of the Soviet Union, it is important to examine the health effects of SES and marital status and other social forces in the nation. Our results reveal that while Russia has a very different past in terms of medicine, public health and economic institutions, it currently faces public health threats that follow similar patterns to those found in Western nations.

The HIM (Health for Izhevsk Men) trial protocol.

BACKGROUND: Russia is one of the very few industrialised countries in the world where life expectancy has been declining. Alcohol has been implicated as a major contributor to the rapid fluctuations observed in male life expectancy since 1985 that have been particularly marked among working-age men. One approach to reducing the alcohol problem in Russia is 'brief interventions' which seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behaviour change. There is limited understanding in Russia of the salience and applicability of Motivational Interviewing (MI), a well-defined brief intervention commonly used to target alcohol-related behaviour, but MI may have important potential for success within the Russian context. METHODS/DESIGN: The study will be an individually randomised two-armed parallel group exploratory trial. The primary hypothesis is that a brief adaptation of MI will be effective in reducing self-reported hazardous drinking at 3 months. The secondary hypothesis is that it will be effective in reducing self-reported past week beverage alcohol consumption, alcohol dependence and related problems at 3 months and at 12 months. MI will also be effective at 12 months in reducing self-reported hazardous drinking, alcohol dependence and related problems, proxy reported hazardous drinking, and recent alcohol use as indicated by bio-markers. Participants are drawn from the Izhevsk Family Study II, with eligibility determined based on proxy reports of hazardous drinking in the past year. All participants undergo a health check, with MI subsequently delivered to those in the intervention arm. Signed consent is obtained from those in the intervention arm at this point. Both groups are then invited for 3 and 12 month follow ups. The control group will not receive any additional intervention. TRIAL REGISTRATION: ISRCTN82405938.

Identifying the determinants of premature mortality in Russia: overcoming a methodological challenge.

BACKGROUND: It is thought that excessive alcohol consumption is related to the high mortality among working age men in Russia. Moreover it has been suggested that alcohol is a key proximate driver of the very sharp fluctuations in mortality seen in this group since the mid-1980s. Designing an individual-level study suitable to address the potential acute effects of alcohol consumption on mortality in Russia has posed a challenge to epidemiologists, especially because of the need to identify factors that could underlie the rapid changes up and down in mortality rates that have been such a distinctive feature of the Russian mortality crisis. In order to address this study question which focuses on exposures acting shortly before sudden death, a cohort would be unfeasibly large and would suffer from recruitment bias. METHODS: Although the situation in Russia is unusual, with a very high death rate characterised by many sudden and apparently unexpected deaths in young men, the methodological problem is common to research on any cause of death where many deaths are sudden. RESULTS: We describe the development of an innovative approach that has overcome some of these challenges: a case-control study employing proxy informants and external data sources to collect information about proximate determinants of mortality. CONCLUSION: This offers a set of principles that can be adopted by epidemiologists studying sudden and unexpected deaths in other settings.

Hazardous alcohol drinking and premature mortality in Russia: a population based case-control study.

BACKGROUND: The reason for the low life expectancy in Russian men and large fluctuations in mortality are unknown. We investigated the contribution of alcohol, and hazardous drinking in particular, to male mortality in a typical Russian city. METHODS: Cases were all deaths in men aged 25-54 years living in Izhevsk occurring between Oct 20, 2003, to Oct 3, 2005. Controls were selected at random from the city population and were frequency matched to deaths by age. Interviews with proxy informants living in the same household as cases were done between Dec 11, 2003, and Nov, 16 2005, and were obtained for 62% (1750/2835) of cases and 57% (1750/3078) of controls. We ascertained frequency and usual amount of beer, wine, and spirits consumed and frequency of consumption of manufactured ethanol-based liquids not intended to be drunk (non-beverage alcohol), and markers of problem drinking. Complete information on markers of problem drinking, frequency of alcohol consumption, education, and smoking was available for 1468 cases and 1496 controls. FINDINGS: 751 (51%) cases were classed as problem drinkers or drank non-beverage alcohol, compared with 192 (13%) controls. The mortality odds ratio (OR) for these men, compared with those who either abstained or were non-problematic beverage drinkers, was 6.0 (95% CI 5.0-7.3) after adjustment for smoking and education. The mortality ORs for drinking non-beverage alcohol in the past year (yes vs no) was 9.2 (7.2-11.7) after adjustment for age. Adjustment for volume of ethanol consumed from beverages lowered the OR to 8.3 (6.5-10.7), and further adjustment for education and smoking reduced it to 7.0 (5.5-9.0). A strong direct gradient with mortality was seen for frequency of non-beverage alcohol drinking independent of volume of beverage ethanol consumed. 43% of mortality was attributable to hazardous drinking (problem drinking or non-beverage alcohol consumption, or both) adjusted for smoking and education. INTERPRETATION: Almost half of all deaths in working age men in a typical Russian city may be accounted for by hazardous drinking. Our analyses provide indirect support for the contention that the sharp fluctuations seen in Russian mortality in the early 1990s could be related to hazardous drinking as indicated by consumption of non-beverage alcohol.

The composition of surrogate alcohols consumed in Russia.

BACKGROUND: In the course of a case-control study examining determinants of premature death among working age men, it became clear that a significant percentage of the population (7.3%) were drinking a variety of surrogate alcohol products (products not legally sold for consumption). In this population, where there is a high death rate from alcohol-related causes, including acute alcohol poisoning, it was important to know what these products contained. METHODS: The identity of products being consumed was identified from the survey of controls. Representative samples were obtained and subjected to analysis using gas chromatography and mass spectrometry to determine their composition. RESULTS: Three broad groups of product were identified: samogon (home-produced spirits); medicinal compounds; and other spirits (mainly sold as aftershaves). Commercially produced vodkas were used for comparison. Samogon contained lower quantities of ethanol than vodka [mean, 39 vs. 44 volumetric percentage (v/v%), respectively] but in addition contained certain toxic long-chain alcohols. Medicinal compounds contained only ethanol, at a higher concentration that vodka (mean, 66 v/v%), while the other spirits, which were also essentially pure ethanol, contained a mean of 94 v/v%. CONCLUSIONS: A significant number of Russian men are drinking products that have either very high concentrations of ethanol or contaminants known to be toxic. These products are untaxed and thus much less expensive than vodka. There is an urgent need for policy responses that target their production and consumption.