SummaryBackgroundAlcohol is an important determinant of the high and fluctuating adult mortality rates in Russia, but cause-specific detail is lacking. Our case–control study investigated the effects of alcohol consumption on male and female cause-specific mortality.MethodsIn three Russian industrial cities with typical 1990s mortality patterns (Tomsk, Barnaul, Biysk), the addresses of 60 416 residents who had died at ages 15–74 years in 1990–2001 were visited in 2001–05. Family members were present for 50 066 decedents; for 48 557 (97%), the family gave proxy information on the decedents' past alcohol use and on potentially confounding factors. Cases (n=43 082) were those certified as dying from causes we judged beforehand might be substantially affected by alcohol or tobacco; controls were the other 5475 decedents. Case versus control relative risks (RRs; calculated as odds ratios by confounder-adjusted logistic regression) were calculated in ever-drinkers, defining the reference category by two criteria: usual weekly consumption always less than 0·5 half-litre bottles of vodka (or equivalent in total alcohol content) and maximum consumption of spirits in 1 day always less than 0·5 half-litre bottles. Other ever-drinkers were classified by usual weekly consumption into three categories: less than one, one to less than three, and three or more (mean 5·4 [SD 1·4]) bottles of vodka or equivalent.FindingsIn men, the three causes accounting for the most alcohol-associated deaths were accidents and violence (RR 5·94, 95% CI 5·35–6·59, in the highest consumption category), alcohol poisoning (21·68, 17·94–26·20), and acute ischaemic heart disease other than myocardial infarction (3·04, 2·73–3·39), which includes some misclassified alcohol poisoning. There were significant excesses of upper aerodigestive tract cancer (3·48, 2·84–4·27) and liver cancer (2·11, 1·64–2·70). Another five disease groups had RRs of more than 3·00 in the highest alcohol category: tuberculosis (4·14, 3·44–4·98), pneumonia (3·29, 2·83–3·83), liver disease (6·21, 5·16–7·47), pancreatic disease (6·69, 4·98–9·00), and ill-specified conditions (7·74, 6·48–9·25). Although drinking was less common in women, the RRs associated with it were generally more extreme. After correction for reporting errors, alcohol-associated excesses accounted for 52% of all study deaths at ages 15–54 years (men 8182 [59%] of 13968, women 1565 [33%] of 4751) and 18% of those at 55–74 years (men 3944 [22%] of 17 536, women 1493 [12%] of 12 302). Allowance for under-representation of extreme drinkers would further increase alcohol-associated proportions. Large fluctuations in mortality from these ten strongly alcohol-associated causes were the main determinants of recent fluctuations in overall mortality in the study region and in Russia as a whole.InterpretationAlcohol-attributable mortality varies by year; in several recent years, alcohol was a cause of more than half of all Russian deaths at ages 15–54 years. Alcohol accounts for most of the large fluctuations in Russian mo...

SummaryBackgroundRussian adults have extraordinarily high rates of premature death. Retrospective enquiries to the families of about 50 000 deceased Russians had found excess vodka use among those dying from external causes (accident, suicide, violence) and eight particular disease groupings. We now seek prospective evidence of these associations.MethodsIn three Russian cities (Barnaul, Byisk, and Tomsk), we interviewed 200 000 adults during 1999–2008 (with 12 000 re-interviewed some years later) and followed them until 2010 for cause-specific mortality. In 151 000 with no previous disease and some follow-up at ages 35–74 years, Poisson regression (adjusted for age at risk, amount smoked, education, and city) was used to calculate the relative risks associating vodka consumption with mortality. We have combined these relative risks with age-specific death rates to get 20-year absolute risks.FindingsAmong 57 361 male smokers with no previous disease, the estimated 20-year risks of death at ages 35–54 years were 16% (95% CI 15–17) for those who reported consuming less than a bottle of vodka per week at baseline, 20% (18–22) for those consuming 1–2·9 bottles per week, and 35% (31–39) for those consuming three or more bottles per week; trend p<0·0001. The corresponding risks of death at ages 55–74 years were 50% (48–52) for those who reported consuming less than a bottle of vodka per week at baseline, 54% (51–57) for those consuming 1–2·9 bottles per week, and 64% (59–69) for those consuming three or more bottles per week; trend p<0·0001. In both age ranges most of the excess mortality in heavier drinkers was from external causes or the eight disease groupings strongly associated with alcohol in the retrospective enquiries. Self-reported drinking fluctuated; of the men who reported drinking three or more bottles of vodka per week who were reinterviewed a few years later, about half (185 of 321) then reported drinking less than one bottle per week. Such fluctuations must have substantially attenuated the apparent hazards of heavy drinking in this study, yet self-reported vodka use at baseline still strongly predicted risk. Among male non-smokers and among females, self-reported heavy drinking was uncommon, but seemed to involve similar absolute excess risks.InterpretationThis large prospective study strongly reinforces other evidence that vodka is a major cause of the high risk of premature death in Russian adults.FundingUK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union, WHO International Agency for Research on Cancer.

The increases in mortality in 1991-94 and in 1998-2003 coincided with economic and societal crisis, while decreases in 1994-98 and 2003-06 correlate with improvement in the economic situation. Excessive alcohol intake is a major cause of premature male Russian mortality, although many alcohol-related deaths are wrongly attributed to diseases of the circulatory system.

Non-small cell lung carcinoma (NSCLC) is the major cause of cancer-associated mortality. Identification of rearrangements in anaplastic lymphoma kinase (ALK) gene is an effective instrument for more effective targeted therapy of NSCLC using ALK inhibitors dramatically raising progression-free survival in the ALK-mutated group of patients. However, the tumors frequently develop resistance to ALK inhibitors. We describe here a case of 48 y.o. male patient with ALK-positive NSCLC who was clinically managed for 6.5 years from the diagnosis. The tumor was surgically resected, but 8 months later multiple brain metastases were discovered. The patient started receiving platinum-based chemotherapy and then was enrolled in a clinical trial of second-generation ALK inhibitor ceritinib, which resulted in a 21 months stabilization. Following disease relapse, the patient was successfully managed for 33 months with different lines of chemo- and local ablative therapies. Chemotherapy regimens, including off-label combination of crizotinib + bevacizumab + docetaxel, were selected using the cancer transcriptome data-guided bioinformatical decision support system Oncobox. These therapies led to additional stabilization for 22 months. Survival of our patient after developing resistance to ALK inhibitor was longer for 16 months than previously reported average survival for such cases. This case shows that transcriptomic-guided sequential personalized prescription of targeted therapies can be effective in terms of survival and quality of life in ALK-mutated NSCLC.

Objectives: Blood-based tests have been shown to be an effective strategy for colorectal cancer (CRC) detection in screening programs. This study was aimed to test the performance of 20 blood markers including tumor antigens, inflammatory markers, and apolipoproteins as well as their combinations. Methods: In total 203 healthy volunteers and 102 patients with CRC were enrolled into the study. Differences between healthy and cancer subjects were evaluated using Wilcoxon rank-sum test. Several multivariate classification algorithms were employed using information about different combinations of biomarkers altered in CRC patients as well as age and gender of the subjects; random sub-sampling cross-validation was done to overcome overfitting problem. Diagnostic performance of single biomarkers and multivariate classification models was evaluated by receiver operating characteristic (ROC) analysis. Results: Of 20 biomarkers, 16 were significantly different between the groups (p-value ≤ 0.001); ApoA1, ApoA2 and ApoA4 levels were decreased, whereas levels of tumor antigens (e.g. carcinoembriogenic antigen) and inflammatory markers (e.g., C-reactive protein) were increased in CRC patients vs. healthy subjects. Combinatorial markers including information about all 16 significant analytes, age and gender of patients, demonstrated better performance over single biomarkers with average accuracy on test datasets ≥95% and area under ROC curve (AUROC) ≥98%. Conclusions: Combinatorial approach was shown to be a valid strategy to improve performance of blood-based CRC diagnostics. Further evaluation of the proposed models in screening programs will be performed to gain a better understanding of their diagnostic value.