Scarcity nationalism during COVID-19: Identifying the impact on trade costs.

During the COVID-19 pandemic, many countries used export and import policy as a tool to expand the availability of scarce critical medical products in the domestic market (scarcity nationalism). This paper assesses the direct and indirect (via trade in intermediates) increases in trade costs of critical medical goods resulting from these uncooperative policies. The results show that scarcity nationalism led to substantial increases in trade costs between February 2020 and December 2021 for most COVID-19 critical medical products, particularly garments (for example, face masks) and ventilators. The exception is vaccines, which saw a reduction in trade costs, which, however, was driven by the reduction in indirect trade costs for high-income countries, consistent with the view of a COVID-19 vaccine production club.

How COVID-19 travels in- and outside of value chains and then affects the stock market: Evidence from China.

The organisation of value chains within and between firms and even countries is an important reason for domestic as well as international travel. Hence, value chains create interdependencies which have to do with economic but also personal interactions between firms and places. The latter means value chains are a springboard for shocks-positive or negative-to travel and other related outcomes. This paper sheds light on how input-output relations in China as one human-interaction-intensive activity can help explain spreading patterns of COVID-19 in the first few months of 2020 in China. We document that COVID-19 at that time spread more intensively where input-output relations were stronger between cities in China, and this contributed to inducing direct and mediated, indirect effects on the stock market.

Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe.

PURPOSE: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer's Disease. METHODS: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. RESULTS: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer's disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-D-aspartate blocker memantine in AUH. CONCLUSION: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer's Disease patients from across Europe.

Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. It affects an estimated 20% of the general population, based on cohort studies of varying size and heterogeneous selection. However, the prevalence and incidence of recorded NAFLD diagnoses in unselected real-world health-care records is unknown. We harmonised health records from four major European territories and assessed age- and sex-specific point prevalence and incidence of NAFLD over the past decade. METHODS: Data were extracted from The Health Improvement Network (UK), Health Search Database (Italy), Information System for Research in Primary Care (Spain) and Integrated Primary Care Information (Netherlands). Each database uses a different coding system. Prevalence and incidence estimates were pooled across databases by random-effects meta-analysis after a log-transformation. RESULTS: Data were available for 17,669,973 adults, of which 176,114 had a recorded diagnosis of NAFLD. Pooled prevalence trebled from 0.60% in 2007 (95% confidence interval: 0.41-0.79) to 1.85% (0.91-2.79) in 2014. Incidence doubled from 1.32 (0.83-1.82) to 2.35 (1.29-3.40) per 1000 person-years. The FIB-4 non-invasive estimate of liver fibrosis could be calculated in 40.6% of patients, of whom 29.6-35.7% had indeterminate or high-risk scores. CONCLUSIONS: In the largest primary-care record study of its kind to date, rates of recorded NAFLD are much lower than expected suggesting under-diagnosis and under-recording. Despite this, we have identified rising incidence and prevalence of the diagnosis. Improved recognition of NAFLD may identify people who will benefit from risk factor modification or emerging therapies to prevent progression to cardiometabolic and hepatic complications.

Assessment of bone-targeting agents use in patients with bone metastasis from breast, lung or prostate cancer using structured and unstructured electronic health records from a regional UK-based hospital.

ObjectiveTo assess use of bone-targeting agents (BTA) in patients with confirmed bone metastases (BM) from breast cancer (BC), non-small cell lung cancer (NSCLC) or prostate cancer (PC). DESIGN: Retrospective cohort study. SETTING: Regional hospital-based oncology database of approximately 2 million patients in England. PARTICIPANTS: Patients aged ≥18 years with a diagnosis of BC, NSCLC or PC as well as BM between 1 January 2007 and 31 December 2018, with follow-up to 30 June 2020 or death; BM diagnosis ascertained from recorded medical codes and unstructured data using natural language processing (NLP). MAIN OUTCOMES MEASURES: Initiation or non-initiation of BTA following BM diagnosis, time from BM diagnosis to BTA initiation, time from first to last BTA, time from last BTA to death. RESULTS: This study included 559 BC, 894 NSCLC and 1013 PC with BM; median age (Q1-Q3) was 65 (52-76), 69 (62-77) and 75 (62-77) years, respectively. NLP identified BM diagnosis from unstructured data for 92% patients with BC, 92% patients with NSCLC and 95% patients with PC. Among patients with BC, NSCLC and PC with BM, 47%, 87% and 88% did not receive a BTA, and 53%, 13% and 12% received at least one BTA, starting a median 65 (27-167), 60 (28-162) and 610 (295-980) days after BM, respectively. Median (Q1-Q3) duration of BTA treatment was 481 (188-816), 89 (49-195) and 115 (53-193) days for patients with BC, NSCLC and PC. For those with a death record, median time from last BTA to death was 54 (26-109) for BC, 38 (17-98) for NSCLC and 112 (44-218) days for PC. CONCLUSION: In this study identifying BM diagnosis from both structured and unstructured data, a high proportion of patients did not receive a BTA. Unstructured data provide new insights on the real-world use of BTA.

Lupus disease activity and the risk of subsequent organ damage and mortality in a large lupus cohort.

OBJECTIVES: To estimate the effect of SLE disease activity, observed over a 12-month period, on the risk of irreversible organ damage and mortality, adjusted for potential confounding factors. METHODS: Patients were enrolled into a prospective cohort study and followed up from 1991. This study retrospectively analyses the data captured in the prospective cohort study. The study population consisted of 350 patients with SLE (meeting four or more of the revised ACR criteria) enrolled at University College Hospital, London lupus clinic. Disease activity was assessed during the observation year using the classic BILAG system and a mean total BILAG score was calculated for that time period. Organ damage outcomes, assessed over a subsequent follow-up period, were based on SLICC/ACR damage index scores and included new damage overall and by specific organ systems (renal, CNS or cardiovascular/musculoskeletal/pulmonary systems) or reaching a serious level of damage (SDI ≥ 3). Adjusted hazard ratios (HRs) for the association between disease activity and subsequent organ damage or mortality were calculated using Cox proportional hazards regression. RESULTS: Disease activity as measured by mean total BILAG score was associated with mortality (HR = 1.15, P = 0.008), new organ damage (HR = 1.08, P = 0.009) and CV/pulmonary or musculoskeletal damage (HR = 1.11, P = 0.007) after adjustment for age, sex, ethnicity, SLE duration, steroid exposure level, NSAID, anti-malarial or immunosuppressant use, renal activity and complement C3 or anti-dsDNA levels. Of these adjustment factors, age, renal activity, immunosuppressant use and pre-existing organ damage were additional independent predictors. CONCLUSIONS: Disease activity as measured by global BILAG score during a 12-month observation period predicts the risk of subsequent organ damage and mortality after adjustment for key covariates.

Design of cohort studies in chronic diseases using routinely collected databases when a prescription is used as surrogate outcome.

BACKGROUND: There has been little research on design of studies based on routinely collected data when the clinical endpoint of interest is not recorded, but can be inferred from a prescription. This often happens when exploring the effect of a drug on chronic diseases. Using the LifeLink claims database in studying the possible anti-inflammatory effects of statins in rheumatoid arthritis (RA), oral steroids (OS) were treated as surrogate of inflammatory flare-ups. We compared two cohort study designs, the first using time to event outcomes and the second using quantitative amount of the surrogate. METHODS: RA patients were extracted from the LifeLink database. In the first study, patients were split into two sub-cohorts based on whether they were using OS within a specified time window of the RA index date (first record of RA). Using Cox models we evaluated the association between time-varying exposure to statins and (i) initiation of OS therapy in the non-users of OS at RA index date and (ii) cessation of OS therapy in the users of OS at RA index date. In the second study, we matched new statin users to non users on age and sex. Zero inflated negative binomial models were used to contrast the number of days' prescriptions of OS in the year following date of statin initiation for the two exposure groups. RESULTS: In the unmatched study, the statin exposure hazard ratio (HR) of initiating OS in the 31451 non-users of OS at RA index date was 0.96(95% CI 0.9,1.1) and the statin exposure HR of cessation of OS therapy in the 6026 users of OS therapy at RA index date was 0.95 (0.87,1.05). In the matched cohort of 6288 RA patients the statin exposure rate ratio for duration on OS therapy was 0.88(0.76,1.02). There was digit preference for outcomes in multiples of 7 and 30 days. CONCLUSIONS: The 'time to event' study design was preferable because it better exploits information on all available patients and provides a degree of robustness toward confounding. We found no convincing evidence that statins reduce inflammation in RA patients.

Dynamic network and own effects on abnormal returns: evidence from China's stock market.

This paper addresses the question of how to model the process of abnormal returns on individual stocks. It postulates a framework, where abnormal returns are generated by a process which features two autoregressive components, one stock-specific and one related to network effects. This process deviates from customary ones in that the parameters are specific to each stock/firm, that the autoregressive process is explicitly modelled instead of using cumulative abnormal returns over a pre-specified window, and that network effects are present. Abandoning either one of those deviations is rejected by data on Chinese stocks in 2018 and 2019, an episode which is significant for an abnormal stock-market returns analysis, as it was characterized by numerous tariff-setting events related to the "trade war" between the USA and China.

Impact of systemic lupus erythematosus disease activity, hydroxychloroquine and NSAID on the risk of subsequent organ system damage and death: analysis in a single US medical centre.

OBJECTIVE: To assess the impact of mild-moderate systemic lupus erythematosus (SLE) disease activity during a 12-month period on the risk of death or subsequent organ system damage. METHODS: 1168 patients with ≥24 months of follow-up from the Hopkins Lupus Cohort were included. Disease activity in a 12-month observation period was calculated using adjusted mean Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI), defined as the area under the curve divided by the time interval. Damage accrual in the follow-up period was defined as change in Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score ≥1 among patients without prior damage. Patients visited the clinic quarterly and had SELENA-SLEDAI and SDI assessed at every visit. RESULTS: During follow-up (median 7 years), 39% of patients accrued new damage in any organ system (7% cardiovascular and 3% renal) and 8% died. In adjusted models, an increased SELENA-SLEDAI score increased the risk of death (HR=1.22, 95% CI 1.13 to 1.32, p<0.001), renal damage (HR=1.24, 95% CI 1.08 to 1.42, p=0.003) and cardiovascular damage (HR=1.17, 95% CI 1.07 to 1.29, p<0.001). Hydroxychloroquine use reduced the risk of death (HR=0.46, 95% CI 0.29 to 0.72, p<0.05) and renal damage (HR=0.30, 95% CI 0.13 to 0.68, p<0.05). Non-steroidal anti-inflammatory drug use increased the risk of cardiovascular damage (HR=1.66, 95% CI 1.04 to 2.63, p<0.05). Without prior damage, an increased adjusted mean SELENA-SLEDAI score increased the risk of overall damage accrual (HR=1.09, 95% CI 1.04 to 1.15, p<0.001). CONCLUSIONS: Each one-unit increase in adjusted mean SELENA-SLEDAI during a 12-month observation period was associated with an increased risk of death and developing cardiovascular and renal damage.

Is there an anti-inflammatory effect of statins in rheumatoid arthritis? Analysis of a large routinely collected claims database.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * The increasing evidence of the anti-inflammatory action of statins has stimulated interest in whether these might be beneficial in disease management of rheumatoid arthritis (RA), a chronic diseases characterized by high levels of inflammation. * The TARA trial (McCarey 2004) suggested a significant reduction in disease activity outcomes in RA patients randomized to atorvastatin compared with those assigned to the placebo harm. * However, as the signal reported by the trial was small, more evidence is needed. WHAT THIS PAPER ADDS: * We investigated the possible anti-inflammatory effect of statins in a cohort of RA patients using a large health insurance claims database. * To our knowledge, this is the largest study ever conducted on the anti-inflammatory effects of statins. * Our data do not show any beneficial effect of statins in reducing disease inflammation in RA patients. AIM: To investigate the possible anti-inflammatory effect of statins in a cohort of rheumatoid arthritis (RA) patients. METHODS: We conducted a cohort study consisting of all patients with at least one claim for RA using LifeLink, a health insurance claims database. Initiation and cessation of oral steroid (OS) therapy were treated as surrogate for inflammatory flare-up and controlled inflammation, respectively. We split the RA patients into two sub-cohorts based on whether they were using OS within a specified time window of the RA index date (first recorded claim for RA in the database). Cox proportional hazard models were used to evaluate the association between time-varying exposure to any statins and (i) initiation of OS therapy in the non-users of OS at RA index date and (ii) cessation of OS therapy in the users of OS at RA index date controlling for potential confounders. RESULTS: We found 31 451 non-users of OS at RA index date and 6026 users of OS within the time window at RA index date. The results on both sub-cohorts were both consistent with no association of statin exposure with the risk of initiation/cessation of OS: the hazard ratio (HR) of initiating OS therapy was 0.96 (95% confidence interval 0.9, 1.01) in the sub-cohort of non-users and the HR of cessation of OS therapy was 0.95 (0.87, 1.05) in the sub-cohort of users of OS therapy at RA diagnosis. CONCLUSIONS: These data do not show any beneficial effect of statins in reducing disease inflammation in RA patients.

Is poverty the mother of crime? Evidence from homicide rates in China.

Income inequality is blamed for being the main driver of violent crime by the majority of the literature. However, earlier work on the topic largely neglects the role of poverty and income levels as opposed to income inequality. The current paper uses all court verdicts for homicide cases in China between 2014 and 2016, as well as various inequality measures calculated from 2005 mini census data together with a host of control variables to shed light on the relationship at the detailed Chinese prefecture-level. The results suggest that it is the poverty and low income level, rather than income inequality, that is positively related to homicide rates. We show that the internal rural-urban migration from more violent localities contributes to the destination cities' homicide rates. The poverty-homicide association implies that instead of "relative deprivation", "absolute deprivation" is mainly responsible for violent crime. Poverty is the mother of crime. -Marcus Aurelius (121-180AD), Emperor of the Roman Empire.

Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: a multi-national multi-database case-control study.

BACKGROUND: Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk. METHODS: A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from electronic health records in the UK, Spain, Denmark and the Netherlands. Conditional logistic regression models were fitted to estimate the risk of dementia. RESULTS: Prior methotrexate use was associated with a lower risk of dementia (OR 0.71, 95% CI 0.52-0.98). Furthermore, methotrexate use with therapy longer than 4 years had the lowest risk of dementia (odds ratio 0.37, 95% CI 0.17-0.79). Sulfasalazine use was not associated with dementia (odds ratio 0.88, 95% CI 0.57-1.37). CONCLUSIONS: Further studies are still required to clarify the relationship between prior methotrexate use and duration as well as biological treatments with dementia risk.

Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults.

OBJECTIVE: To estimate the risk of acute myocardial infarction (AMI) or stroke in adults with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). DESIGN: Matched cohort study. SETTING: Population based, electronic primary healthcare databases before 31 December 2015 from four European countries: Italy (n=1 542 672), Netherlands (n=2 225 925), Spain (n=5 488 397), and UK (n=12 695 046). PARTICIPANTS: 120 795 adults with a recorded diagnosis of NAFLD or NASH and no other liver diseases, matched at time of NAFLD diagnosis (index date) by age, sex, practice site, and visit, recorded at six months before or after the date of diagnosis, with up to 100 patients without NAFLD or NASH in the same database. MAIN OUTCOME MEASURES: Primary outcome was incident fatal or non-fatal AMI and ischaemic or unspecified stroke. Hazard ratios were estimated using Cox models and pooled across databases by random effect meta-analyses. RESULTS: 120 795 patients with recorded NAFLD or NASH diagnoses were identified with mean follow-up 2.1-5.5 years. After adjustment for age and smoking the pooled hazard ratio for AMI was 1.17 (95% confidence interval 1.05 to 1.30; 1035 events in participants with NAFLD or NASH, 67 823 in matched controls). In a group with more complete data on risk factors (86 098 NAFLD and 4 664 988 matched controls), the hazard ratio for AMI after adjustment for systolic blood pressure, type 2 diabetes, total cholesterol level, statin use, and hypertension was 1.01 (0.91 to 1.12; 747 events in participants with NAFLD or NASH, 37 462 in matched controls). After adjustment for age and smoking status the pooled hazard ratio for stroke was 1.18 (1.11 to 1.24; 2187 events in participants with NAFLD or NASH, 134 001 in matched controls). In the group with more complete data on risk factors, the hazard ratio for stroke was 1.04 (0.99 to 1.09; 1666 events in participants with NAFLD, 83 882 in matched controls) after further adjustment for type 2 diabetes, systolic blood pressure, total cholesterol level, statin use, and hypertension. CONCLUSIONS: The diagnosis of NAFLD in current routine care of 17.7 million patient appears not to be associated with AMI or stroke risk after adjustment for established cardiovascular risk factors. Cardiovascular risk assessment in adults with a diagnosis of NAFLD is important but should be done in the same way as for the general population.

Identifying Cases of Type 2 Diabetes in Heterogeneous Data Sources: Strategy from the EMIF Project.

Due to the heterogeneity of existing European sources of observational healthcare data, data source-tailored choices are needed to execute multi-data source, multi-national epidemiological studies. This makes transparent documentation paramount. In this proof-of-concept study, a novel standard data derivation procedure was tested in a set of heterogeneous data sources. Identification of subjects with type 2 diabetes (T2DM) was the test case. We included three primary care data sources (PCDs), three record linkage of administrative and/or registry data sources (RLDs), one hospital and one biobank. Overall, data from 12 million subjects from six European countries were extracted. Based on a shared event definition, sixteeen standard algorithms (components) useful to identify T2DM cases were generated through a top-down/bottom-up iterative approach. Each component was based on one single data domain among diagnoses, drugs, diagnostic test utilization and laboratory results. Diagnoses-based components were subclassified considering the healthcare setting (primary, secondary, inpatient care). The Unified Medical Language System was used for semantic harmonization within data domains. Individual components were extracted and proportion of population identified was compared across data sources. Drug-based components performed similarly in RLDs and PCDs, unlike diagnoses-based components. Using components as building blocks, logical combinations with AND, OR, AND NOT were tested and local experts recommended their preferred data source-tailored combination. The population identified per data sources by resulting algorithms varied from 3.5% to 15.7%, however, age-specific results were fairly comparable. The impact of individual components was assessed: diagnoses-based components identified the majority of cases in PCDs (93-100%), while drug-based components were the main contributors in RLDs (81-100%). The proposed data derivation procedure allowed the generation of data source-tailored case-finding algorithms in a standardized fashion, facilitated transparent documentation of the process and benchmarking of data sources, and provided bases for interpretation of possible inter-data source inconsistency of findings in future studies.

Endogenous risk-taking and physical appearance of sex workers.

Previous research found that physical appearance affects the risk-taking of sex workers through offering unprotected services. This paper utilizes a large individual-level data set covering 16,583 pay-for-sex contracts in 2011 and 2012 by 2,517 female suppliers in Germany. Results based on instrumental variables suggest that the incentive for risk-taking is about twice as high than when assuming random assignment of risk-taking.

Relationship between polycystic ovaries, body mass index and insulin resistance.

BACKGROUND: To investigate insulin levels in lean and overweight women with and without polycystic ovaries. An observational, cross-sectional study at The Northem General Hospital, Sheffield, UK. METHODS: Sixty-eight women born at Jessop Hospital, Sheffield, between 1952 and 1953 were divided into four groups according to the status of their polycystic ovaries and body mass index: either > or approximately 25. Therefore, this was an unselected sample, unlike previous studies that have recruited from endocrine clinics or similar. Subjects underwent pelvic ultrasonography to visualize their ovaries in order to diagnose or exclude polycystic ovaries. They all underwent a short insulin tolerance test. RESULTS: Women with a body mass index > 25 and with polycystic ovaries were the most insulin resistant. Women with a body mass index of < or = ?25 and with normal ovaries were the most insulin sensitive. Women with a body mass index < or = ?25 and polycystic ovaries were the more resistant than those with a body mass index > 25 and with normal ovaries. CONCLUSION: Obesity increases insulin resistance, and the presence of polycystic ovaries increases insulin resistance. The presence of polycystic ovaries appears to have a stronger influence than obesity on insulin resistance. This is the first study to demonstrate these relationships using unselected volunteers.