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Introduction: Antibiotic resistance poses a threat to public health and healthcare systems. Escherichia coli causes more bacteraemia episodes in England than any other bacterial species. This study aimed to estimate the burden of E. coli bacteraemia and associated antibiotic resistance in the secondary care setting. Materials and methods: This was a retrospective cohort study, with E. coli bacteraemia as the main exposure of interest. Adult hospital in-patients, admitted to acute NHS hospitals between July 2011 and June 2012 were included. English national surveillance and administrative datasets were utilised. Cox proportional hazard, subdistribution hazard and multistate models were constructed to estimate rate of discharge, rate of in-hospital death and excess length of stay, with a unit bed day cost applied to the latter to estimate cost burden from the healthcare system perspective. Results: 14,042 E. coli bacteraemia and 8,919,284 non-infected inpatient observations were included. E. coli bacteraemia was associated with an increased rate of in-hospital death across all models, with an adjusted subdistribution hazard ratio of 5.88 (95% CI: 5.62–6.15). Resistance was not found to be associated with in-hospital mortality once adjusting for patient and hospital covariates. However, resistance was found to be associated with an increased excess length of stay. This was especially true for third generation cephalosporin (1.58 days excess length of stay, 95% CI: 0.84–2.31) and piperacillin/tazobactam resistance (1.23 days (95% CI: 0.50–1.95)). The annual cost of E. coli bacteraemia was estimated to be £14,346,400 (2012 £), with third-generation cephalosporin resistance associated with excess costs per infection of £420 (95% CI: 220–630). Conclusions: E. coli bacteraemia places a statistically significant burden on patient health and the hospital sector in England. Resistance to front-line antibiotics increases length of stay; increasing the cost burden of such infections in the secondary care setting. [ABSTRACT FROM AUTHOR]

Background: Despite the relative ease with which breech presentation can be identified through ultrasound screening, the assessment of foetal presentation at term is often based on clinical examination only. Due to limitations in this approach, many women present in labour with an undiagnosed breech presentation, with increased risk of foetal morbidity and mortality. This study sought to determine the cost effectiveness of universal ultrasound scanning for breech presentation near term (36 weeks of gestational age [wkGA]) in nulliparous women.Methods and Findings: The Pregnancy Outcome Prediction (POP) study was a prospective cohort study between January 14, 2008 and July 31, 2012, including 3,879 nulliparous women who attended for a research screening ultrasound examination at 36 wkGA. Foetal presentation was assessed and compared for the groups with and without a clinically indicated ultrasound. Where breech presentation was detected, an external cephalic version (ECV) was routinely offered. If the ECV was unsuccessful or not performed, the women were offered either planned cesarean section at 39 weeks or attempted vaginal breech delivery. To compare the likelihood of different mode of deliveries and associated long-term health outcomes for universal ultrasound to current practice, a probabilistic economic simulation model was constructed. Parameter values were obtained from the POP study, and costs were mainly obtained from the English National Health Service (NHS). One hundred seventy-nine out of 3,879 women (4.6%) were diagnosed with breech presentation at 36 weeks. For most women (96), there had been no prior suspicion of noncephalic presentation. ECV was attempted for 84 (46.9%) women and was successful in 12 (success rate: 14.3%). Overall, 19 of the 179 women delivered vaginally (10.6%), 110 delivered by elective cesarean section (ELCS) (61.5%) and 50 delivered by emergency cesarean section (EMCS) (27.9%). There were no women with undiagnosed breech presentation in labour in the entire cohort. On average, 40 scans were needed per detection of a previously undiagnosed breech presentation. The economic analysis indicated that, compared to current practice, universal late-pregnancy ultrasound would identify around 14,826 otherwise undiagnosed breech presentations across England annually. It would also reduce EMCS and vaginal breech deliveries by 0.7 and 1.0 percentage points, respectively: around 4,196 and 6,061 deliveries across England annually. Universal ultrasound would also prevent 7.89 neonatal mortalities annually. The strategy would be cost effective if foetal presentation could be assessed for £19.80 or less per woman. Limitations to this study included that foetal presentation was revealed to all women and that the health economic analysis may be altered by parity.Conclusions: According to our estimates, universal late pregnancy ultrasound in nulliparous women (1) would virtually eliminate undiagnosed breech presentation, (2) would be expected to reduce foetal mortality in breech presentation, and (3) would be cost effective if foetal presentation could be assessed for less than £19.80 per woman. [ABSTRACT FROM AUTHOR]

Many disciplines of scholarship are interested in the Relative Age Effect (RAE), whereby age-banding confers advantages on older members of the cohort over younger ones. Most research does not test this relationship in a manner consistent with theory (which requires a decline in frequency across the cohort year), instead resorting to non-parametric, non-directional approaches. In this article, the authors address this disconnect, provide an overview of the benefits associated with Poisson regression modelling, and two managerially useful measures for quantifying RAE bias, namely the Indices of Discrimination and Wastage. In a tutorial-like exposition, applications and extensions of this approach are illustrated using data on professional soccer players competing in the top two tiers of the “Big Five” European football leagues in the search to identify paragon clubs, leagues, and countries from which others may learn to mitigate this form of age-discrimination in the talent identification process. As with OLS regression, Poisson regression may include more than one independent variable. In this way we test competing explanations of RAE; control for unwanted sources of covariation; model interaction effects (that different clubs and countries may not all be subject to RAE to the same degree); and test for non-monotonic versions of RAE suggested in the literature. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is assoicated with high mortality and measures to improve risk stratification and early identification have been urgently called for. This study investigated whether an electronic clinical prediction rule (CPR) combined with an AKI e-alert could reduce hospital-acquired AKI (HA-AKI) and improve associated outcomes. Methods and findings: A controlled before-and-after study included 30,295 acute medical admissions to two adult non-specialist hospital sites in the South of England (two ten-month time periods, 2014–16); all included patients stayed at least one night and had at least two serum creatinine tests. In the second period at the intervention site a CPR flagged those at risk of AKI and an alert was generated for those with AKI; both alerts incorporated care bundles. Patients were followed-up until death or hospital discharge. Primary outcome was change in incident HA-AKI. Secondary outcomes in those developing HA-AKI included: in-hospital mortality, AKI progression and escalation of care. On difference-in-differences analysis incidence of HA-AKI reduced (odds ratio [OR] 0.990, 95% CI 0.981–1.000, P = 0.049). In-hospital mortality in HA-AKI cases reduced on difference-in-differences analysis (OR 0.924, 95% CI 0.858–0.996, P = 0.038) and unadjusted analysis (27.46% pre vs 21.67% post, OR 0.731, 95% CI 0.560–0.954, P = 0.021). Mortality in those flagged by the CPR significantly reduced (14% pre vs 11% post intervention, P = 0.008). Outcomes for community-acquired AKI (CA-AKI) cases did not change. A number of process measures significantly improved at the intervention site. Limitations include lack of randomization, and generalizability will require future investigation. Conclusions: In acute medical admissions a multi-modal intervention, including an electronically integrated CPR alongside an e-alert for those developing HA-AKI improved in-hospital outcomes. CA-AKI outcomes were not affected. The study provides a template for investigations utilising electronically generated prediction modelling. Further studies should assess generalisability and cost effectiveness. Trial registration: Clinicaltrials.org . [ABSTRACT FROM AUTHOR]

Background: A modal shift to cycling has the potential to reduce greenhouse gas emissions and provide health co-benefits. Methods, models, and tools are needed to estimate the potential for cycling uptake and communicate to policy makers the range of impacts this would have.Methods and Findings: The Impacts of Cycling Tool (ICT) is an open source model with a web interface for visualising travel patterns and comparing the impacts of different scenarios of cycling uptake. It is currently applied to England. The ICT allows users to visualise individual and trip-level data from the English National Travel Survey (NTS), 2004-2014 sample, 132,000 adults. It models scenarios in which there is an increase in the proportion of the population who cycle regularly, using a distance-based propensity approach to model which trips would be cycled. From this, the model estimates likely impact on travel patterns, health, and greenhouse gas emissions. Estimates of nonoccupational physical activity are generated by fusing the NTS with the English Active People Survey (APS, 2013-2014, 559,515 adults) to create a synthetic population. Under 'equity' scenarios, we investigate what would happen if cycling levels increased equally among all age and gender categories, as opposed to in proportion to the profile of current cyclists. Under electric assist bike (pedelecs or 'e-bike') scenarios, the probability of cycling longer trips increases, based on the e-bike data from the Netherlands, 2013-2014 Dutch Travel Survey (50,868 adults).Outcomes are presented across domains including transport (trip duration and trips by mode), health (physical activity levels, years of life lost), and car transport-related CO2 emissions. Results can be visualised for the whole population and various subpopulations (region, age, gender, and ethnicity). The tool is available at www.pct.bike/ict. If the proportion of the English population who cycle regularly increased from 4.8% to 25%, then there would be notable reductions in car miles and passenger related CO2 emissions (2.2%) and health benefits (2.1% reduction in years of life lost due to premature mortality). If the new cyclists had access to e-bikes, then mortality reductions would be similar, while the reduction in car miles and CO2 emissions would be larger (2.7%). If take-up of cycling occurred equally by gender and age (under 80 years), then health benefits would be marginally greater (2.2%) but reduction in CO2 slightly smaller (1.8%). The study is limited by the quality and comparability of the input data (including reliance on self-report behaviours). As with all modelling studies, many assumptions are required and potentially important pathways excluded (e.g. injury, air pollution, and noise pollution).Conclusion: This study demonstrates a generalisable approach for using travel survey data to model scenarios of cycling uptake that can be applied to a wide range of settings. The use of individual-level data allows investigation of a wide range of outcomes, and variation across subgroups. Future work should investigate the sensitivity of results to assumptions and omissions, and if this varies across setting. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to describe ethnic variations in infant mortality and explore the contribution of area deprivation, mother’s country of birth, and prematurity to these variations. Methods: We analyzed routine birth and death data on singleton live births (gestational age≥22 weeks) in England and Wales, 2006–2012. Infant mortality by ethnic group was analyzed using logistic regression with adjustment for sociodemographic characteristics and gestational age. Results: In the 4,634,932 births analyzed, crude infant mortality rates were higher in Pakistani, Black Caribbean, Black African, and Bangladeshi infants (6.92, 6.00, 5.17 and 4.40 per 1,000 live births, respectively vs. 2.87 in White British infants). Adjustment for maternal sociodemographic characteristics changed the results little. Further adjustment for gestational age strongly attenuated the risk in Black Caribbean (OR 1.02, 95% CI 0.89–1.17) and Black African infants (1.17, 1.06–1.29) but not in Pakistani (2.32, 2.15–2.50), Bangladeshi (1.47, 1.28–1.69), and Indian infants (1.24, 1.11–1.38). Ethnic variations in infant mortality differed significantly between term and preterm infants. At term, South Asian groups had higher risks which cannot be explained by sociodemographic characteristics. In preterm infants, adjustment for degree of prematurity (<28, 28–31, 32–33, 34–36 weeks) fully explained increased risks in Black but not Pakistani and Bangladeshi infants. Sensitivity analyses with further adjustment for small for gestational age, or excluding deaths due to congenital anomalies did not fully explain the excess risk in South Asian groups. Conclusions: Higher infant mortality in South Asian and Black infants does not appear to be explained by sociodemographic characteristics. Higher proportions of very premature infants appear to explain increased risks in Black infants but not in South Asian groups. Strategies targeting the prevention and management of preterm birth in Black groups and suboptimal birthweight and modifiable risk factors for congenital anomalies in South Asian groups might help reduce ethnic inequalities in infant mortality. [ABSTRACT FROM AUTHOR]

Introduction: During the 2013–2014 influenza season, Public Health England extended routine influenza vaccination to all 2- and 3-year-old children in England. To estimate the impact of this change in policy on influenza-related morbidity and mortality, we developed a disease transmission and surveillance model informed by real-world data. Methods: We combined real-world and literature data sources to construct a model of influenza transmission and surveillance in England. Data were obtained for four influenza seasons, starting with the 2010–2011 season. Bayesian inference was used to estimate model parameters on a season-by-season basis to assess the impact of targeting 2- and 3-year-old children for influenza vaccination. This provided the basis for the construction of counterfactual scenarios comparing vaccination rates of ~2% and ~35% in the 2- and 3- year-old population to estimate reductions in general practitioner (GP) influenza-like-illness (ILI) consultations, respiratory hospitalizations and deaths in the overall population. Results: Our model was able to replicate the main patterns of influenza across the four seasons as observed through laboratory surveillance data. Targeting 2- and 3-year-old children for influenza vaccination resulted in reductions in the general population of between 6.2–9.9% in influenza-attributable GP ILI consultations, 6.1–10.7% in influenza-attributable respiratory hospitalizations, and 5.7–9.4% in influenza-attributable deaths. The decrease in influenza-attributable ILI consultations represents a reduction of between 4.5% and 7.3% across all ILI consultations. The reduction in influenza-attributable respiratory hospitalizations represents a reduction of between 1.2% and 2.3% across all respiratory hospitalizations. Reductions in influenza-attributable respiratory deaths represent a reduction of between 0.9% and 2.4% in overall respiratory deaths. Conclusion: This study has provided evidence that extending routine influenza vaccination to all healthy children aged 2 and 3 years old leads to benefits in terms of reduced utilization of healthcare resources and fewer respiratory health outcomes and deaths. [ABSTRACT FROM AUTHOR]

Background: After traumatic brain injury (TBI), the ability of cerebral vessels to appropriately react to changes in arterial blood pressure (pressure reactivity) is impaired, leaving patients vulnerable to cerebral hypo- or hyperperfusion. Although, the traditional pressure reactivity index (PRx) has demonstrated that impaired pressure reactivity is associated with poor patient outcome, PRx is sometimes erratic and may not be reliable in various clinical circumstances. Here, we introduce a more robust transform-based wavelet pressure reactivity index (wPRx) and compare its performance with the widely used traditional PRx across 3 areas: its stability and reliability in time, its ability to give an optimal cerebral perfusion pressure (CPPopt) recommendation, and its relationship with patient outcome.Methods and Findings: Five hundred and fifteen patients with TBI admitted in Addenbrooke's Hospital, United Kingdom (March 23rd, 2003 through December 9th, 2014), with continuous monitoring of arterial blood pressure (ABP) and intracranial pressure (ICP), were retrospectively analyzed to calculate the traditional PRx and a novel wavelet transform-based wPRx. wPRx was calculated by taking the cosine of the wavelet transform phase-shift between ABP and ICP. A time trend of CPPopt was calculated using an automated curve-fitting method that determined the cerebral perfusion pressure (CPP) at which the pressure reactivity (PRx or wPRx) was most efficient (CPPopt_PRx and CPPopt_wPRx, respectively). There was a significantly positive relationship between PRx and wPRx (r = 0.73), and wavelet wPRx was more reliable in time (ratio of between-hour variance to total variance, wPRx 0.957 ± 0.0032 versus PRx and 0.949 ± 0.047 for PRx, p = 0.002). The 2-hour interval standard deviation of wPRx (0.19 ± 0.07) was smaller than that of PRx (0.30 ± 0.13, p < 0.001). wPRx performed better in distinguishing between mortality and survival (the area under the receiver operating characteristic [ROC] curve [AUROC] for wPRx was 0.73 versus 0.66 for PRx, p = 0.003). The mean difference between the patients' CPP and their CPPopt was related to outcome for both calculation methods. There was a good relationship between the 2 CPPopts (r = 0.814, p < 0.001). CPPopt_wPRx was more stable than CPPopt_PRx (within patient standard deviation 7.05 ± 3.78 versus 8.45 ± 2.90; p < 0.001). Key limitations include that this study is a retrospective analysis and only compared wPRx with PRx in the cohort of patients with TBI. Prior prospective validation is required to better assess clinical utility of this approach.Conclusions: wPRx offers several advantages to the traditional PRx: it is more stable in time, it yields a more consistent CPPopt recommendation, and, importantly, it has a stronger relationship with patient outcome. The clinical utility of wPRx should be explored in prospective studies of critically injured neurological patients. [ABSTRACT FROM AUTHOR]

Modelling length of stay in neonatal care is vital to inform service planning and the counselling of parents. Preterm babies, at the highest risk of mortality, can have long stays in neonatal care and require high resource use. Previous work has incorporated babies that die into length of stay estimates, but this still overlooks the levels of care required during their stay. This work incorporates all babies, and the levels of care they require, into length of stay estimates. Data were obtained from the National Neonatal Research Database for singleton babies born at 24–31 weeks gestational age discharged from a neonatal unit in England from 2011 to 2014. A Cox multistate model, adjusted for gestational age, was used to consider a baby’s two competing outcomes: death or discharge from neonatal care, whilst also considering the different levels of care required: intensive care; high dependency care and special care. The probabilities of receiving each of the levels of care, or having died or been discharged from neonatal care are presented graphically overall and adjusted for gestational age. Stacked predicted probabilities produced for each week of gestational age provide a useful tool for clinicians when counselling parents about length of stay and for commissioners when considering allocation of resources. Multistate modelling provides a useful method for describing the entire neonatal care pathway, where rates of in-unit mortality can be high. For a healthcare service focussed on costs, it is important to consider all babies that contribute towards workload, and the levels of care they require. [ABSTRACT FROM AUTHOR]

Background: Low birthweight (LBW) is associated with increased mortality in infancy, but its association with mortality in later childhood and adolescence is less clear. We investigated the association between birthweight and all-cause mortality and identified major causes of mortality for different birthweight groups.Methods and Findings: We conducted a population study of all live births occurring in England and Wales between 1 January 1993 and 31 December 2011. Following exclusions, the 12,355,251 live births were classified by birthweight: 500-1,499 g (very LBW [VLBW], n = 139,608), 1,500-2,499 g (LBW, n = 759,283), 2,500-3,499 g (n = 6,511,411), and ≥3,500 g (n = 4,944,949). The association of birthweight group with mortality in infancy (<1 y of age) and childhood/adolescence (1-18 y of age) was quantified, with and without covariates, through hazard ratios using Cox regression. International Classification of Diseases codes identified causes of death. In all, 74,890 (0.61%) individuals died between birth and 18 y of age, with 23% of deaths occurring after infancy. Adjusted hazard ratios for infant deaths were 145 (95% CI 141, 149) and 9.8 (95% CI 9.5, 10.1) for the VLBW and LBW groups, respectively, compared to the ≥3,500 g group. The respective hazard ratios for death occurring at age 1-18 y were 6.6 (95% CI 6.1, 7.1) and 2.9 (95% CI 2.8, 3.1). Male gender, the youngest and oldest maternal age bands, multiple births, and deprivation (Index of Multiple Deprivation score) also contributed to increased deaths in the VLBW and LBW groups in both age ranges. In infancy, perinatal factors, particularly respiratory issues and infections, explained 84% and 31% of deaths in the VLBW and LBW groups, respectively; congenital malformations explained 36% and 23% in the LBW group and ≥2,500 g groups (2,500-3,499 g and ≥3,500 g groups combined), respectively. Central nervous system conditions explained 20% of deaths in childhood/adolescence in the VLBW group, with deaths from neoplasms and external conditions increasingly prevalent in the 1,500-2,499 g and ≥2,500 g birthweight groups. The study would have benefited had we had access to information on gestational age and maternal smoking, but since the former is highly correlated with birthweight and the latter with deprivation, we believe that our findings remain robust despite these shortcomings.Conclusions: LBW is associated with infant and later child and adolescent mortality, with perinatal factors and congenital malformations explaining many of the deaths. By understanding and ameliorating the influences of upstream exposures such as maternal smoking and deprivation, later mortality can be decreased by reducing the delivery of vulnerable infants with LBW. [ABSTRACT FROM AUTHOR]

Background: Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years. Method: A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results. Results: The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust. Conclusions: Vaccinating immunocompetent individuals aged ≥65 years with PCV13 is efficacious. However the absolute incidence of vaccine-type disease will likely become very low due to wider benefits of the childhood PCV13 vaccination programme, such that a specific PCV13 vaccination programme targeting the immunocompetent elderly would not be cost-effective. [ABSTRACT FROM AUTHOR]

Introduction: While evidence that alcohol pricing policies reduce alcohol-related health harm is robust, and alcohol taxation increases are a WHO "best buy" intervention, there is a lack of research comparing the scale and distribution across society of health impacts arising from alternative tax and price policy options. The aim of this study is to test whether four common alcohol taxation and pricing strategies differ in their impact on health inequalities.Methods and Findings: An econometric epidemiological model was built with England 2014/2015 as the setting. Four pricing strategies implemented on top of the current tax were equalised to give the same 4.3% population-wide reduction in total alcohol-related mortality: current tax increase, a 13.4% all-product duty increase under the current UK system; a value-based tax, a 4.0% ad valorem tax based on product price; a strength-based tax, a volumetric tax of £0.22 per UK alcohol unit (= 8 g of ethanol); and minimum unit pricing, a minimum price threshold of £0.50 per unit, below which alcohol cannot be sold. Model inputs were calculated by combining data from representative household surveys on alcohol purchasing and consumption, administrative and healthcare data on 43 alcohol-attributable diseases, and published price elasticities and relative risk functions. Outcomes were annual per capita consumption, consumer spending, and alcohol-related deaths. Uncertainty was assessed via partial probabilistic sensitivity analysis (PSA) and scenario analysis. The pricing strategies differ as to how effects are distributed across the population, and, from a public health perspective, heavy drinkers in routine/manual occupations are a key group as they are at greatest risk of health harm from their drinking. Strength-based taxation and minimum unit pricing would have greater effects on mortality among drinkers in routine/manual occupations (particularly for heavy drinkers, where the estimated policy effects on mortality rates are as follows: current tax increase, -3.2%; value-based tax, -2.9%; strength-based tax, -6.1%; minimum unit pricing, -7.8%) and lesser impacts among drinkers in professional/managerial occupations (for heavy drinkers: current tax increase, -1.3%; value-based tax, -1.4%; strength-based tax, +0.2%; minimum unit pricing, +0.8%). Results from the PSA give slightly greater mean effects for both the routine/manual (current tax increase, -3.6% [95% uncertainty interval (UI) -6.1%, -0.6%]; value-based tax, -3.3% [UI -5.1%, -1.7%]; strength-based tax, -7.5% [UI -13.7%, -3.9%]; minimum unit pricing, -10.3% [UI -10.3%, -7.0%]) and professional/managerial occupation groups (current tax increase, -1.8% [UI -4.7%, +1.6%]; value-based tax, -1.9% [UI -3.6%, +0.4%]; strength-based tax, -0.8% [UI -6.9%, +4.0%]; minimum unit pricing, -0.7% [UI -5.6%, +3.6%]). Impacts of price changes on moderate drinkers were small regardless of income or socioeconomic group. Analysis of uncertainty shows that the relative effectiveness of the four policies is fairly stable, although uncertainty in the absolute scale of effects exists. Volumetric taxation and minimum unit pricing consistently outperform increasing the current tax or adding an ad valorem tax in terms of reducing mortality among the heaviest drinkers and reducing alcohol-related health inequalities (e.g., in the routine/manual occupation group, volumetric taxation reduces deaths more than increasing the current tax in 26 out of 30 probabilistic runs, minimum unit pricing reduces deaths more than volumetric tax in 21 out of 30 runs, and minimum unit pricing reduces deaths more than increasing the current tax in 30 out of 30 runs). Study limitations include reducing model complexity by not considering a largely ineffective ban on below-tax alcohol sales, special duty rates covering only small shares of the market, and the impact of tax fraud or retailer non-compliance with minimum unit prices.Conclusions: Our model estimates that, compared to tax increases under the current system or introducing taxation based on product value, alcohol-content-based taxation or minimum unit pricing would lead to larger reductions in health inequalities across income groups. We also estimate that alcohol-content-based taxation and minimum unit pricing would have the largest impact on harmful drinking, with minimal effects on those drinking in moderation. [ABSTRACT FROM AUTHOR]

Background: The etiology of Crohn's disease and multiple sclerosis is unknown. Genetic susceptibility and environmental factors are believed to play a role in both diseases., Objectives: To compare the long-term time trends of the two diseases and thus gain insight about their etiology., Methods: We analyzed mortality data of Crohn's disease and multiple sclerosis from Canada, England, Italy, the Netherlands, Switzerland, and the United States during the past 60 years. Age-period-cohort (APC) analyses based on logit models served to disentangle the separate influences of age, period, and cohort effects on the overall time trends., Results: The long-term time trends of Crohn's disease and multiple sclerosis have been shaped by strikingly similar birth-cohort patterns. In both diseases alike, mortality increased in all generations born prior to 1910. It peaked among generations born between 1910 and 1930 and then declined in all subsequent generations. Similar birth-cohort patterns of Crohn's disease and multiple sclerosis were found in each country analyzed separately., Conclusion: The birth-cohort patterns indicate that the development of Crohn's disease and multiple sclerosis is influenced by exposure to environmental risk factors during an early period of life. These environmental risk factors may be similar or even identical in Crohn's disease and multiple sclerosis.