GANGs: Generative Adversarial Network Games

Generative Adversarial Networks (GAN) have become one of the most successful frameworks for unsupervised generative modeling. As GANs are difficult to train much research has focused on this. However, very little of this research has directly exploited game-theoretic techniques. We introduce Generative Adversarial Network Games (GANGs), which explicitly model a finite zero-sum game between a generator ($G$) and classifier ($C$) that use mixed strategies. The size of these games precludes exact solution methods, therefore we define resource-bounded best responses (RBBRs), and a resource-bounded Nash Equilibrium (RB-NE) as a pair of mixed strategies such that neither $G$ or $C$ can find a better RBBR. The RB-NE solution concept is richer than the notion of `local Nash equilibria' in that it captures not only failures of escaping local optima of gradient descent, but applies to any approximate best response computations, including methods with random restarts. To validate our approach, we solve GANGs with the Parallel Nash Memory algorithm, which provably monotonically converges to an RB-NE. We compare our results to standard GAN setups, and demonstrate that our method deals well with typical GAN problems such as mode collapse, partial mode coverage and forgetting

Ranitidine Use and Incident Cancer in a Multinational Cohort

Importance: Ranitidine, the most widely used histamine-2 receptor antagonist (H2RA), was withdrawn because of N-nitrosodimethylamine impurity in 2020. Given the worldwide exposure to this drug, the potential risk of cancer development associated with the intake of known carcinogens is an important epidemiological concern. Objective: To examine the comparative risk of cancer associated with the use of ranitidine vs other H2RAs. Design, Setting, and Participants: This new-user active comparator international network cohort study was conducted using 3 health claims and 9 electronic health record databases from the US, the United Kingdom, Germany, Spain, France, South Korea, and Taiwan. Large-scale propensity score (PS) matching was used to minimize confounding of the observed covariates with negative control outcomes. Empirical calibration was performed to account for unobserved confounding. All databases were mapped to a common data model. Database-specific estimates were combined using random-effects meta-analysis. Participants included individuals aged at least 20 years with no history of cancer who used H2RAs for more than 30 days from January 1986 to December 2020, with a 1-year washout period. Data were analyzed from April to September 2021. Exposure: The main exposure was use of ranitidine vs other H2RAs (famotidine, lafutidine, nizatidine, and roxatidine). Main Outcomes and Measures: The primary outcome was incidence of any cancer, except nonmelanoma skin cancer. Secondary outcomes included all cancer except thyroid cancer, 16 cancer subtypes, and all-cause mortality. Results: Among 1 183 999 individuals in 11 databases, 909 168 individuals (mean age, 56.1 years; 507 316 [55.8%] women) were identified as new users of ranitidine, and 274 831 individuals (mean age, 58.0 years; 145 935 [53.1%] women) were identified as new users of other H2RAs. Crude incidence rates of cancer were 14.30 events per 1000 person-years (PYs) in ranitidine users and 15.03 events per 1000 PYs among other H2RA users. After PS matching, cancer risk was similar in ranitidine compared with other H2RA users (incidence, 15.92 events per 1000 PYs vs 15.65 events per 1000 PYs; calibrated meta-analytic hazard ratio, 1.04; 95% CI, 0.97-1.12). No significant associations were found between ranitidine use and any secondary outcomes after calibration. Conclusions and Relevance: In this cohort study, ranitidine use was not associated with an increased risk of cancer compared with the use of other H2RAs. Further research is needed on the long-term association of ranitidine with cancer development.</p

How well can post‐traumatic stress disorder be predicted from pre‐trauma risk factors? An exploratory study in the WHO World Mental Health Surveys

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108700/1/wps20150.pd

The Epidemiology of Alcohol Use Disorders Cross-Nationally: Findings from the World Mental Health Surveys

Background: Prevalences of Alcohol Use Disorders (AUDs) and Mental Health Disorders (MHDs) in many individual countries have been reported but there are few cross-national studies. The WHO World Mental Health (WMH) Survey Initiative standardizes methodological factors facilitating comparison of the prevalences and associated factors of AUDs in a large number of countries to identify differences and commonalities. Methods: Lifetime and 12-month prevalence estimates of DSM-IV AUDs, MHDs, and associations were assessed in the 29 WMH surveys using the WHO CIDI 3.0. Results: Prevalence estimates of alcohol use and AUD across countries and WHO regions varied widely. Mean lifetime prevalence of alcohol use in all countries combined was 80%, ranging from 3.8% to 97.1%. Combined average population lifetime and 12-month prevalence of AUDs were 8.6% and 2.2% respectively and 10.7% and 4.4% among non-abstainers. Of individuals with a lifetime AUD, 43.9% had at least one lifetime MHD and 17.9% of respondents with a lifetime MHD had a lifetime AUD. For most comorbidity combinations, the MHD preceded the onset of the AUD. AUD prevalence was much higher for men than women. 15% of all lifetime AUD cases developed before age 18. Higher household income and being older at time of interview, married, and more educated, were associated with a lower risk for lifetime AUD and AUD persistence. Conclusions: Prevalence of alcohol use and AUD is high overall, with large variation worldwide. The WMH surveys corroborate the wide geographic consistency of a number of well-documented clinical and epidemiological findings and patterns

Association of Cohort and Individual Substance Use With Risk of Transitioning to Drug Use, Drug Use Disorder, and Remission From Disorder: Findings From the World Mental Health Surveys

Importance: Limited empirical research has examined the extent to which cohort-level prevalence of substance use is associated with the onset of drug use and transitioning into greater involvement with drug use. Objective: To use cross-national data to examine time-space variation in cohort-level drug use to assess its associations with onset and transitions across stages of drug use, abuse, dependence, and remission. Design, Setting, and Participants: The World Health Organization World Mental Health Surveys carried out cross-sectional general population surveys in 25 countries using a consistent research protocol and assessment instrument. Adults from representative household samples were interviewed face-to-face in the community in relation to drug use disorders. The surveys were conducted between 2001 and 2015. Data analysis was performed from July 2017 to July 2018. Main Outcomes and Measures: Data on timing of onset of lifetime drug use, DSM-IV drug use disorders, and remission from these disorders was assessed using the Composite International Diagnostic Interview. Associations of cohort-level alcohol prevalence and drug use prevalence were examined as factors associated with these transitions. Results: Among the 90 027 respondents (48.1% [SE, 0.2%] men; mean [SE] age, 42.1 [0.1] years), 1 in 4 (24.8% [SE, 0.2%]) reported either illicit drug use or extramedical use of prescription drugs at some point in their lifetime, but with substantial time-space variation in this prevalence. Among users, 9.1% (SE, 0.2%) met lifetime criteria for abuse, and 5.0% (SE, 0.2%) met criteria for dependence. Individuals who used 2 or more drugs had an increased risk of both abuse (odds ratio, 5.17 [95% CI, 4.66-5.73]; P \u3c .001) and dependence (odds ratio, 5.99 [95% CI, 5.02-7.16]; P \u3c .001) and reduced probability of remission from abuse (odds ratio, 0.86 [95% CI, 0.76-0.98]; P = .02). Birth cohort prevalence of drug use was also significantly associated with both initiation and illicit drug use transitions; for example, after controlling for individuals’ experience of substance use and demographics, for each additional 10% of an individual’s cohort using alcohol, a person’s odds of initiating drug use increased by 28% (odds ratio, 1.28 [95% CI, 1.26-1.31]). Each 10% increase in a cohort’s use of drug increased individual risk by 12% (1.12 [95% CI, 1.11-1.14]). Conclusions and Relevance: Birth cohort substance use is associated with drug use involvement beyond the outcomes of individual histories of alcohol and other drug use. This has important implications for understanding pathways into and out of problematic drug use

Characteristics and outcomes of 627 044 COVID-19 patients living with and without obesity in the United States, Spain, and the United Kingdom

Altres ajuts: This research received partial support from the National Institute for Health Research (NIHR) Oxford Biomedical Research Center (BRC), US National Institutes of Health, US Department of Veterans Affairs, Janssen Research & Development, and IQVIA. The University of Oxford received funding related to this work from the Bill & Melinda Gates Foundation (Investment ID INV016201 and INV-019257). APU has received funding from the Medical Research Council (MRC) [MR/K501256/1, MR/N013468/1] and Fundación Alfonso Martín Escudero (FAME) (APU). VINCI [VA HSR RES 13-457] (SLD, MEM, KEL). JCEL has received funding from the Medical Research Council (MR/K501256/1) and Versus Arthritis (21605). MR is funded by Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant program [grant number: 2017/1630]A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity. We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status. We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8−40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0−33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity. We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies

Cross-national epidemiology of DSM-IV major depressive episode

Background: Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low-to middle-income countries in the World Mental Health Survey Initiative. Methods: Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults. Results: The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2: 1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low-to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed. Conclusions: MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.(NIH/NIMH) United States National Institute of Mental Health[R01MH070884]John D. and Catherine T. MacArthur FoundationPfizer FoundationUSA Public Health Service[R13-MH066849]USA Public Health Service[R01-MH069864]USA Public Health Service[R01 DA016558](NIH) Fogarty International Center[FIRCA R03-TW006481]PAHO Pan American Health OrganizationEli Lilly & Company FoundationOrtho-McNeil Pharmaceutical, Inc.GlaxoSmithKlineSanofi-AventisBristol-Myers SquibbState of Brazil Research Foundation (FAPESP)[03/00204-3]Ministry of Social ProtectionEuropean Commission[QLG5-1999-01042]European Commission[SANCO 2004123]Piedmont Region (Italy)Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Spain[FIS 00/0028]Spanish Ministerio de Ciencia y Tecnologia[SAF 2000-158-CE]Departament de Salut, Generalitat de Catalunya, SpainInstituto de Salud Carlos III[CIBER CB06/02/0046]Instituto de Salud Carlos III[RETICS RD06/0011 REM-TAP]Government of IndiaWHOMinistry of HealthIsrael National Institute for Health Policy and Health Services ResearchNational Insurance Institute of IsraelJapan Ministry of Health, Labour and Welfare[H13-Shogai-023]Japan Ministry of Health, Labour and Welfare[H14-Tokubetsu-026]Japan Ministry of Health, Labour and Welfare[H16-Kokoro-013]Lebanese Ministry of Public HealthWHO (Lebanon)(NIH) Fogarty International, anonymous private donations to IDRAAC, LebanonJanssen CilagEli LillyRocheNovartisNational Institute of Psychiatry Ramon de la Fuente[INPRFMDIES 4280]CNPq National Council on Science and Technology[CONACyT-G30544-H]PanAmerican Health Organization (PAHO)New Zealand Ministry of Health, Alcohol Advisory CouncilHealth Research Council(NIH/NIMH) USA National Institute of Mental Health[R01-MH059575](NIH/NIMH) USA National Institute of Mental Health[RO1-MH61905]National Institute of Drug AbuseSouth African Department of HealthUniversity of MichiganNational Institute of Mental Health (NIH/NIMH)[U01-MH60220]National Institute of Drug Abuse (NIDA)Substance Abuse and Mental Health Services Administration (SAMHSA)Robert Wood Johnson Foundation (RWJF)[044708]John W. Alden TrustsAnalysis Group Inc.Eli Lilly CompanyEPI-QJohnson & Johnson PharmaceuticalsOrtho-McNeil Janssen Scientific AffairsPfizer Inc.Shire USA, Inc

Multinational patterns of second line antihyperglycaemic drug initiation across cardiovascular risk groups:federated pharmacoepidemiological evaluation in LEGEND-T2DM

Objective: To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design: Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting: 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.Participants: 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.Exposure: The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measures: The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.Results: 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.Conclusions: Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.</p

Phylogenetic history demonstrates two different lineages of dengue type 1 virus in Colombia

Background: Dengue Fever is one of the most important viral re-emergent diseases affecting about 50 million people around the world especially in tropical and sub-tropical countries. In Colombia, the virus was first detected in the earliest 70′s when the disease became a major public health concern. Since then, all four serotypes of the virus have been reported. Although most of the huge outbreaks reported in this country have involved dengue virus serotype 1 (DENV-1), there are not studies about its origin, genetic diversity and distribution. Results: We used 224 bp corresponding to the carboxyl terminus of envelope (E) gene from 74 Colombian isolates in order to reconstruct phylogenetic relationships and to estimate time divergences. Analyzed DENV-1 Colombian isolates belonged to the formerly defined genotype V. Only one virus isolate was clasified in the genotype I, likely representing a sole introduction that did not spread. The oldest strains were closely related to those detected for the first time in America in 1977 from the Caribbean and were detected for two years until their disappearance about six years later. Around 1987, a split up generated 2 lineages that have been evolving separately, although not major aminoacid changes in the analyzed region were found. Conclusion: DENV-1 has been circulating since 1978 in Colombia. Yet, the phylogenetic relationships between strains isolated along the covered period of time suggests that viral strains detected in some years, although belonging to the same genotype V, have different recent origins corresponding to multiple re-introduction events of viral strains that were circulating in neighbor countries. Viral strains used in the present study did not form a monophyletic group, which is evidence of a polyphyletic origin. We report the rapid spread patterns and high evolution rate of the different DENV-1 lineages