Is duration of residence a proxy for acculturation? The case of health risk behaviors among international immigrants.

AIMS: Among international immigrants, health changes by duration of residence are commonly interpreted as an expression of acculturation to the receiving country context. This study compares changes in immigrants' health risk behaviors by duration of residence to changes by acculturation levels, in order to assess whether duration of residence can be regarded as a proxy for acculturation. METHODS: Using data from a previous systematic review, we identified 17 quantitative studies examining changes in alcohol, tobacco and drug use, physical inactivity, and diet by both duration of residence and acculturation level in the same population. We compared the directionality and consistency of these associations through tabulation and vote counting. RESULTS: The majority of studies reported no or inconsistent changes in health risk behaviors by duration of residence versus by acculturation, including with opposite directionality. Four studies reported significant estimates with consistent directionality, while five reported consistent, non-significant estimates. CONCLUSIONS: Our findings suggest that duration of residence should not be used as a proxy for acculturation when studying health risk behaviors among immigrants. Researchers should consider additional time-dependent factors to explain behavioral changes by duration of residence.

Effects of the COVID-19 pandemic on mental health, working, and life situation of employees in the Swedish hospitality industry.

Introduction: Previous studies reported that the coronavirus disease (COVID-19) pandemic has negatively affected the mental health of employees in the hospitality industry internationally, however, its effect in Sweden has not been studied. Unlike several other countries, Sweden never enforced a lockdown. Restaurants, bars, and hotels could remain open and host a limited number of guests but had to abide by certain restrictions. Methods: A cross-sectional survey was distributed among hospitality industry employees containing questions regarding the perceived effects of the pandemic on the respondents' working and life situations and their physical and psychological health. The sample consisted of 699 individuals, with a response rate of 47.9%. Results: Although several respondents had been laid off or furloughed, the majority of the sample remained at the same employer. However, more than half of the respondents reported that their economic situation had deteriorated. Compared to before the pandemic, 38.1% experienced elevated levels of stress, 48.3% experienced elevated levels of worry, and 31.4% reported worsened mood. A deteriorating personal economy and difficulty in following COVID-19-related restrictions at work were associated with the worsening of these three mental health aspects. While the fear of becoming infected with COVID-19 was related to higher levels of stress, the fear of infecting others was related to higher levels of worry. Conclusion: Although Sweden imposed less strict measures than most other countries, the personal economy and mental health of hospitality workers were negatively affected by the COVID-19 pandemic.

Health Risk Behaviours by Immigrants' Duration of Residence: A Systematic Review and Meta-Analysis.

Objectives: The aim was to systematically review and synthesise international evidence on changes in health risk behaviours by immigrants' duration of residence. Methods: We searched literature databases for peer-reviewed quantitative studies published from 2000 to 2019, examining alcohol, drug and tobacco use; physical inactivity; and dietary habits by duration of residence. Results: Narrative synthesis indicated that immigrants tend to adopt health risk behaviours with longer residence in North America, with larger variation in effect sizes and directionality in other contexts. Random-effects meta-analyses examining the pooled effect across all receiving countries and immigrant groups showed lower odds of smoking (OR 0.54, 0.46-0.63, I 2 = 68.7%) and alcohol use (OR 0.61, 0.47-0.75, I 2 = 93.5%) and higher odds of physical inactivity (OR 1.71, 1.40-2.02, I 2 = 99.1%) among immigrants than natives, but did not provide support for a universal trend by duration of residence. Conclusion: Findings suggest that duration of residence could serve as an effective instrument to monitor immigrants' health changes. However, differences in receiving country contexts and immigrant populations' composition seem to be important to predict the level and direction of behavioural change. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO CRD42018108881.

Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress.

The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors.

PFKFB3 Inhibition Sensitizes DNA Crosslinking Chemotherapies by Suppressing Fanconi Anemia Repair.

Replicative repair of interstrand crosslinks (ICL) generated by platinum chemotherapeutics is orchestrated by the Fanconi anemia (FA) repair pathway to ensure resolution of stalled replication forks and the maintenance of genomic integrity. Here, we identify novel regulation of FA repair by the cancer-associated glycolytic enzyme PFKFB3 that has functional consequences for replication-associated ICL repair and cancer cell survival. Inhibition of PFKFB3 displays a cancer-specific synergy with platinum compounds in blocking cell viability and restores sensitivity in treatment-resistant models. Notably, the synergies are associated with DNA-damage-induced chromatin association of PFKFB3 upon cancer transformation, which further increases upon platinum resistance. FA pathway activation triggers the PFKFB3 assembly into nuclear foci in an ATR- and FANCM-dependent manner. Blocking PFKFB3 activity disrupts the assembly of key FA repair factors and consequently prevents fork restart. This results in an incapacity to replicate cells to progress through S-phase, an accumulation of DNA damage in replicating cells, and fork collapse. We further validate PFKFB3-dependent regulation of FA repair in ex vivo cultures from cancer patients. Collectively, targeting PFKFB3 opens up therapeutic possibilities to improve the efficacy of ICL-inducing cancer treatments.

The γ-tubulin meshwork assists in the recruitment of PCNA to chromatin in mammalian cells.

Changes in the location of γ-tubulin ensure cell survival and preserve genome integrity. We investigated whether the nuclear accumulation of γ-tubulin facilitates the transport of proliferating cell nuclear antigen (PCNA) between the cytosolic and the nuclear compartment in mammalian cells. We found that the γ-tubulin meshwork assists in the recruitment of PCNA to chromatin. Also, decreased levels of γ-tubulin reduce the nuclear pool of PCNA. In addition, the γ-tubulin C terminus encodes a PCNA-interacting peptide (PIP) motif, and a γ-tubulin-PIP-mutant affects the nuclear accumulation of PCNA. In a cell-free system, PCNA and γ-tubulin formed a complex. In tumors, there is a significant positive correlation between TUBG1 and PCNA expression. Thus, we report a novel mechanism that constitutes the basis for tumor growth by which the γ-tubulin meshwork maintains indefinite proliferation by acting as an opportune scaffold for the transport of PCNA from the cytosol to the chromatin.

Targeting CX3CR1 Suppresses the Fanconi Anemia DNA Repair Pathway and Synergizes with Platinum.

The C-X3-C motif chemokine receptor 1 (CX3CR1, fractalkine receptor) is associated with neoplastic transformation, inflammation, neurodegenerative diseases and aging, and the small molecule inhibitor KAND567 targeting CX3CR1 (CX3CR1i) is evaluated in clinical trials for acute systemic inflammation upon SARS-CoV-2 infections. Here we identify a hitherto unknown role of CX3CR1 in Fanconi anemia (FA) pathway mediated repair of DNA interstrand crosslinks (ICLs) in replicating cells. FA pathway activation triggers CX3CR1 nuclear localization which facilitates assembly of the key FA protein FANCD2 into foci. Interfering with CX3CR1 function upon ICL-induction results in inability of replicating cells to progress from S phase, replication fork stalling and impaired chromatin recruitment of key FA pathway factors. Consistent with defective FA repair, CX3CR1i results in increased levels of residual cisplatin-DNA adducts and decreased cell survival. Importantly, CX3CR1i synergizes with platinum agents in a nonreversible manner in proliferation assays including platinum resistant models. Taken together, our results reveal an unanticipated interplay between CX3CR1 and the FA pathway and show for the first time that a clinical-phase small molecule inhibitor targeting CX3CR1 might show benefit in improving responses to DNA crosslinking chemotherapeutics.

Social network characteristics and alcohol use by ethnic origin: An ego-based network study on peer similarity, social relationships, and co-existing drinking habits among young Swedes.

The study explores how social network determinants relate to the prevalence and frequency of alcohol use among peer dyads. It is studied how similar alcohol habits co-exist among persons (egos) and their peers (alters) when socio-demographic similarity (e.g., in ethnic origin), network composition and other socio-cultural aspects were considered. Data was ego-based responses derived from a Swedish national survey with a cohort of 23-year olds. The analytical sample included 7987 ego-alter pairs, which corresponds to 2071 individuals (egos). A so-called dyadic design was applied i.e., all components of the analysis refer to ego-alter pairs (dyads). Multilevel multinomial-models were used to analyse similarity in alcohol habits in relation to ego-alter similarity in ethnic background, religious beliefs, age, sex, risk-taking, educational level, closure in network, duration, and type of relationship, as well as interactions between ethnicity and central network characteristics. Ego-alter similarity in terms of ethnic origin, age and sex was associated with ego-alter similarity in alcohol use. That both ego and alters were non-religious and were members of closed networks also had an impact on similarity in alcohol habits. It was concluded that network similarity might be an explanation for the co-existence of alcohol use among members of peer networks.

Home and away: mortality among Finnish-born migrants in Sweden compared to native Swedes and Finns residing in Finland.

BACKGROUND: Most first-generation migrants have lower mortality compared to the native population. Finnish-born migrants in Sweden instead have higher mortality; possibly because of health behaviours established before migration. To increase our understanding of this excess mortality, we compared the cause-specific mortality of Finnish migrants in Sweden to both the native population of Sweden and the native Finnish population residing in Finland. METHODS: We used Swedish and Finnish register data, applying propensity score matching techniques to account for differences in sociodemographic characteristics between the migrants, Swedes and Finns. The index population were Finnish migrants aged 40-60, residing in Sweden in 1995. We compared patterns of all-cause, alcohol- and smoking-related, and cardiovascular disease mortality across the groups in the period 1996-2007. RESULTS: Finnish migrant men in Sweden had lower all-cause mortality compared to Finnish men but higher mortality compared to the Swedish men. The same patterns were observed for alcohol-related, smoking-related and cardiovascular disease mortality. Among women, all three groups had similar levels of all-cause mortality. However, Finnish migrant women had higher alcohol-related mortality than Swedish women, similar to Finnish women. Conversely, migrant women had similar levels of smoking-related mortality to Swedish women, lower than Finnish women. CONCLUSIONS: Finnish-born migrants residing in Sweden have mortality patterns that are typically in between the mortality patterns of the native populations in their country of origin and destination. Both the country of origin and destination need to be considered in order to better understand migrant health.

Health risk behaviours among migrants by duration of residence: protocol for a systematic review and meta-analysis.

INTRODUCTION: International migrants' health has often been found to deteriorate in new countries, partly due to changes in health risk behaviours such as alcohol consumption, tobacco use, physical inactivity, and poor dietary habits. However, limited efforts have been made to comprehensively evaluate the extent to which migrants adopt unhealthy risk behaviours with longer duration of residence. This systematic review and meta-analysis will summarise evidence on international migrants' behavioural patterns by duration of residence in multiple country contexts. METHODS AND ANALYSIS: PubMed/MEDLINE, Web of Science and ProQuest databases will be searched for quantitative or mixed-method observational studies published in peer-reviewed scientific journals between 1 January 2000 and 31 December 2019. Studies comparing foreign-born individuals by duration of residence will be included. Information on study characteristics, descriptive statistics and measures of effect will be extracted. All included studies will be quality assessed using a modified Newcastle-Ottawa scale. The review will include narrative synthesis and, if sufficient and comparable data are available, random effects meta-analyses. The review will be conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. ETHICS AND DISSEMINATION: Ethical approval is not required since previously published information from peer-reviewed studies will be assessed. The results of this review will be published in peer-reviewed journals and presented at scientific conferences. Other forms of dissemination will include communication to broader audiences using well-established channels, including through university-based press releases. Progress will be regularly updated on the International Prospective Register of Systematic Reviews to ensure full transparency. PROSPERO REGISTRATION NUMBER: CRD42018108881.

Intergenerational transmission of alcohol misuse: mediation and interaction by school performance in a Swedish birth cohort.

BACKGROUND: Children whose parents misuse alcohol have increased risks of own alcohol misuse in adulthood. Though most attain lower school marks, some still perform well in school, which could be an indicator of resilience with protective potential against negative health outcomes. Accordingly, the aim of this study was to examine the processes of mediation and interaction by school performance regarding the intergenerational transmission of alcohol misuse. METHODS: Data were drawn from a prospective Swedish cohort study of children born in 1953 (n=14 608). Associations between parental alcohol misuse (ages 0-19) and participants' own alcohol misuse in adulthood (ages 20-63) were examined by means of Cox regression analysis. Four-way decomposition was used to explore mediation and interaction by school performance in grade 6 (age 13), grade 9 (age 16) and grade 12 (age 19). RESULTS: Mediation and/or interaction by school performance accounted for a substantial proportion of the association between parental alcohol misuse and own alcohol misuse in adulthood (58% for performance in grade 6, 27% for grade 9 and 30% for grade 12). Moreover, interaction effects appeared to be more important for the outcome than mediation. CONCLUSION: Above-average school performance among children whose parents misused alcohol seems to reflect processes of resilience with the potential to break the intergenerational transmission of alcohol misuse. Four-way decomposition offers a viable approach to disentangle processes of interaction from mediation, representing a promising avenue for future longitudinal research.

Societal costs of venous thromboembolism and subsequent major bleeding events: a national register-based study.

AIMS: Detailed evidence on the societal costs of venous thromboembolism (VTE), i.e. deep vein thrombosis (DVT) and pulmonary embolism (PE), and of subsequent major bleeding events, e.g. intracranial and gastrointestinal bleedings, is limited. The objective was to estimate the average 3-year societal event costs attributable to VTE and subsequent major bleedings in Denmark. METHODS AND RESULTS: Based on nationwide Danish registers, each incident patient diagnosed with VTE in the period from 2004 to 2016 was identified and matched with four non-VTE patients by nearest-neighbour propensity score matching. For bleeding patients, the reference cohort was VTE patients without bleedings. Event costs in terms of VTE, DVT, PE, and major bleedings in VTE patients were measured by the 'difference-in-actual-cost' method within 3 years after the incidence. Societal costs included healthcare costs (primary care, hospital, and prescription medicine), municipality home care services, and production loss. The study population included 74 137 VTE incident patients (DVT: 43 099; PE: 31 038), and 4887 VTE patients with a major bleeding within 3 years from VTE diagnosis. The 3-year attributable societal VTE event costs were 40 024 EUR (DVT: 34 509 EUR; PE: 50 083 EUR) with 53% of these costs appearing in the first incident year. Similar results for major bleedings were 51 168 EUR with 46% of these costs appearing in the first incident year. CONCLUSION: The societal costs of VTE and subsequent major bleedings are substantial and ought to be considered. Estimated costs of events may be informative in evaluating the impact of preventive interventions targeting VTE and subsequent major bleedings.

Cost Burden of Crohn's Disease and Ulcerative Colitis in the 10-Year Period Before Diagnosis-A Danish Register-Based Study From 2003-2015.

BACKGROUND: The diagnostic delay in inflammatory bowel disease (IBD) is well known, yet the costs associated with diagnoses before IBD diagnosis have not yet been reported. This study explored societal costs and disease diagnoses 10 years before Crohn's disease (CD) and ulcerative colitis (UC) diagnosis in Denmark. METHODS: This national register study included patients diagnosed between 2003 and 2015 identified in the Danish National Patient Registry (NPR) and controls who were individually matched on age and sex from the general population. Societal costs included health care services, prescription medicine, home care services, and labor productivity loss. Prediagnostic hospital contact occurring before CD or UC diagnosis was identified using the NPR. Average annual costs per individual were calculated before the patient's first CD or UC diagnosis. A 1-sample t test was then applied to determine significance in differences between cases and controls. RESULTS: Among CD (n = 9019) and UC patients (n = 20,913) the average societal costs were higher throughout the entire 10-year period before the diagnosis date compared with the general population. The difference increased over time and equaled €404 for CD patients and €516 for UC patients 10 years before diagnosis and €3377 and €2960, respectively, in the year before diagnosis. Crohn's disease and UC patients had significantly more diagnoses before their CD and UC diagnosis compared with the general population. CONCLUSIONS: Compared with the general population, the societal costs and number of additional diagnoses among CD and UC patients were substantially higher in the 10-year period before diagnosis.

Societal costs due to meningococcal disease: a national registry-based study.

PURPOSE: Limited detailed evidence exists on the societal costs of meningococcal disease. The objective of this study was to estimate the average 5-year societal cost of events attributable to meningococcal disease in Denmark. METHODS: The study was based on the nationwide Danish registries. Incident patients diagnosed with meningococcal disease were identified and each matched with two controls, using direct matching on age, gender, and level of education. Siblings constituted a secondary control population where one patient was matched with one sibling control without meningococcal disease. Costs related to health care in the primary and secondary sectors, prescription medicine, municipality home care services and costs of production loss, ie, estimated loss of yearly earnings, were included (1997-2015). RESULTS: The incidence of meningococcal disease fluctuated between 1980 and 2015. The average attributable societal costs were highest the first year after diagnosis, with costs equaling USD 18,920 per event in the primary study population (matched controls) and USD 16,169 in the secondary study population (sibling controls). Hospital admission costs accounted for 65% and production loss for 30%; however, having a lifetime perspective and including loss due to premature death further increase the costs of meningococcal disease events. CONCLUSION: The costs of meningococcal disease are substantial, and the estimated costs of event may be informative in evaluating the impact of preventive interventions targeting meningococcal disease.

Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination.

The glycolytic PFKFB3 enzyme is widely overexpressed in cancer cells and an emerging anti-cancer target. Here, we identify PFKFB3 as a critical factor in homologous recombination (HR) repair of DNA double-strand breaks. PFKFB3 rapidly relocates into ionizing radiation (IR)-induced nuclear foci in an MRN-ATM-γH2AX-MDC1-dependent manner and co-localizes with DNA damage and HR repair proteins. PFKFB3 relocalization is critical for recruitment of HR proteins, HR activity, and cell survival upon IR. We develop KAN0438757, a small molecule inhibitor that potently targets PFKFB3. Pharmacological PFKFB3 inhibition impairs recruitment of ribonucleotide reductase M2 and deoxynucleotide incorporation upon DNA repair, and reduces dNTP levels. Importantly, KAN0438757 induces radiosensitization in transformed cells while leaving non-transformed cells unaffected. In summary, we identify a key role for PFKFB3 enzymatic activity in HR repair and present KAN0438757, a selective PFKFB3 inhibitor that could potentially be used as a strategy for the treatment of cancer.

Distinct mechanistic responses to replication fork stalling induced by either nucleotide or protein deprivation.

Incidents that slow or stall replication fork progression, collectively known as replication stress, represent a major source of spontaneous genomic instability. Here, we determine the requirement for global protein biosynthesis on DNA replication and associated downstream signaling. We study this response side by side with dNTP deprivation; one of the most commonly used means to investigate replication arrest and replicative stress. Our in vitro interrogations reveal that inhibition of translation by cycloheximide (CHX) rapidly impairs replication fork progression without decoupling helicase and polymerase activities or inducing DNA damage. In line with this, protein deprivation stress does not activate checkpoint signaling. In contrast to the direct link between insufficient dNTP pools and genome instability, our findings suggest that replication forks remain stable during short-term protein deficiency. We find that replication forks initially endure fluctuations in protein supply in order to efficiently resume DNA synthesis upon reversal of the induced protein deprivation stress. These results reveal distinct cellular responses to replication arrest induced by deprivation of either nucleotides or proteins.

Crystal Structure of the Emerging Cancer Target MTHFD2 in Complex with a Substrate-Based Inhibitor.

To sustain their proliferation, cancer cells become dependent on one-carbon metabolism to support purine and thymidylate synthesis. Indeed, one of the most highly upregulated enzymes during neoplastic transformation is MTHFD2, a mitochondrial methylenetetrahydrofolate dehydrogenase and cyclohydrolase involved in one-carbon metabolism. Because MTHFD2 is expressed normally only during embryonic development, it offers a disease-selective therapeutic target for eradicating cancer cells while sparing healthy cells. Here we report the synthesis and preclinical characterization of the first inhibitor of human MTHFD2. We also disclose the first crystal structure of MTHFD2 in complex with a substrate-based inhibitor and the enzyme cofactors NAD+ and inorganic phosphate. Our work provides a rationale for continued development of a structural framework for the generation of potent and selective MTHFD2 inhibitors for cancer treatment. Cancer Res; 77(4); 937-48. ©2017 AACR.

Changes in alcohol-related harm in Sweden after increasing alcohol import quotas and a Danish tax decrease--an interrupted time-series analysis for 2000-2007.

BACKGROUND: Denmark decreased its tax on spirits by 45% on 1 October 2003. Shortly thereafter, on 1 January 2004, Sweden increased its import quotas of privately imported alcohol, allowing travellers to bring in much larger amounts of alcohol from other European Union countries. Although these changes were assumed to increase alcohol-related harm in Sweden, particularly among people living close to Denmark, analyses based on survey data collected before and after these changes have not supported this assumption. The present article tests whether alcohol-related harm in southern Sweden was affected by these changes by analysing other indicators of alcohol-related harm, e.g. harm recorded in different kinds of registers. METHODS: Interrupted time-series analysis was performed with monthly data on cases of hospitalization due to acute alcohol poisoning, number of reported violent assaults and drunk driving for the years 2000-07 in southern Sweden using the northern parts of Sweden as a control and additionally controlling for two earlier major changes in quotas. RESULTS: The findings were not consistent with respect to whether alcohol-related harm increased in southern Sweden after the decrease in Danish spirits tax and the increase in Swedish alcohol import quotas. On the one hand, an increase in acute alcohol poisonings was found, particularly in the 50-69 years age group, on the other hand, no increase was found in violent assaults and drunk driving. CONCLUSIONS: The present results raise important questions about the association between changes in availability and alcohol-related harms. More research using other methodological approaches and data is needed to obtain a comprehensive picture of what actually happened in southern Sweden.

Changes in alcohol availability, price and alcohol-related problems and the collectivity of drinking cultures: what happened in southern and northern Sweden?

AIMS: The aims of this study were to study whether alcohol-related self-reported problems follow the same pattern of changes in alcohol consumption in southern Sweden, assumed to be affected by a decrease in Danish spirits tax and by an increase in Swedish travellers' import quotas, and to study whether the results obtained for southern and northern Sweden follow the predictions of Skog's theory of collectivity of drinking cultures. METHODS: Analysis was carried out on a sample from the Swedish general population from southern and northern Sweden separately. Two indices such as impaired self-control/dependent behaviour and extrinsic problems for alcohol-related problems were computed and analysed in terms of sex, age, income and alcohol consumption level. RESULTS: Although there were no huge changes in the number of persons reporting alcohol-related problems, the general trend in data for various subpopulations was a decrease in the southern site and an increase in the northern site. In the northern site, the increase in alcohol consumption among men also showed an increase in alcohol-related problems. However, various population subgroups changed in different directions and did not move in concert over the population distribution. CONCLUSIONS: Analysis confirmed that alcohol-related problems, according to the two indices used, followed a similar pattern to alcohol consumption, but less divergent. A version of Skog's theory applied on alcohol-related problems could not confirm that alcohol-related problems did not change collectively within the population.

Alcohol consumption in southern Sweden after major decreases in Danish spirits taxes and increases in Swedish travellers' quotas.

BACKGROUND: In 2003, Denmark lowered its tax on spirits, and in 2004, Sweden increased its traveller import quotas. AIM: The aim of the study was to determine whether these two changes increased self-reported alcohol consumption in southern Sweden, which is located near Denmark. METHOD: Data were collected through telephone interviews with the general population between 2003 and 2006. Individuals aged 16-80 years were interviewed. Some lived in southern Sweden, others in the northern region, which was assumed to be unaffected by the policy changes and was thus used as a control site. Analyses were performed for the total population as well as by sex, age, socio-economic group and consumption pattern. RESULTS: The expected results were not found: alcohol consumption in southern Sweden had not changed. The few statistically significant changes found in southern Sweden indicated decreases. In the north, however, consumption seemed to have increased. CONCLUSION: In addition to the two policy changes mentioned above, other changes seem to have affected alcohol consumption in Sweden. It is possible, however, that the policy changes have affected population groups not reached by the survey, and thus other types of data need to be analysed before drawing any far-reaching conclusions.