Implementation of a national smoke-free prison policy: an economic evaluation within the Tobacco in Prisons (TIPs) study.

OBJECTIVE: To determine the cost-effectiveness of a smoke-free prison policy in Scotland, through assessments of the trade-offs between costs (healthcare and non-healthcare-related expenditure) and outcomes (health and non-health-related non-monetary consequences) of implementing the policy. DESIGN: A health economic evaluation consisting of three analyses (cost-consequence, cost-effectiveness and cost-utility), from the perspectives of the healthcare payer, prison service, people in custody and operational staff, assessed the trade-offs between costs and outcomes. Costs associated with the implementation of the policy, healthcare resource use and personal spend on nicotine products were considered, alongside health and non-health outcomes. The cost-effectiveness of the policy was evaluated over 12-month and lifetime horizons (short term and long term). SETTING: Scotland's national prison estate. PARTICIPANTS: People in custody and operational prison staff. INTERVENTION: Implementation of a comprehensive (indoor and outdoor) smoke-free policy. MAIN OUTCOME MEASURES: Concentration of secondhand smoke, health-related quality of life (health utilities and quality-adjusted life-years (QALY)) and various non-health outcomes (eg, incidents of assaults and fires). RESULTS: The short-term analyses suggest cost savings for people in custody and staff, improvements in concentration of secondhand smoke, with no consistent direction of change across other outcomes. The long-term analysis demonstrated that implementing smoke-free policy was cost-effective over a lifetime for people in custody and staff, with approximate cost savings of £28 000 and £450, respectively, and improvement in health-related quality of life of 0.971 QALYs and 0.262, respectively. CONCLUSION: Implementing a smoke-free prison policy is cost-effective over the short term and long term for people in custody and staff.

Salt loading decreases urinary excretion and increases intracellular accumulation of uromodulin in stroke-prone spontaneously hypertensive rats.

Uromodulin (UMOD) is the most abundant renal protein secreted into urine by the thick ascending limb (TAL) epithelial cells of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants and hypertension. We aimed to dissect the role of dietary salt in renal UMOD excretion in normotension and chronic hypertension. Normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) (n=8/sex/strain) were maintained on 1% NaCl for 3 weeks. A subset of salt-loaded SHRSP was treated with nifedipine. Salt-loading in SHRSP increased blood pressure (ΔSBP 35 ± 5 mmHg, P<0.0001) and kidney injury markers such as kidney injury marker-1 (KIM-1; fold change, FC 3.4; P=0.003), neutrophil gelatinase-associated lipocalin (NGAL; FC, 2.0; P=0.012) and proteinuria. After salt-loading there was a reduction in urinary UMOD excretion in WKY and SHRSP by 26 and 55% respectively, compared with baseline. Nifedipine treatment reduced blood pressure (BP) in SHRSP, however, did not prevent salt-induced reduction in urinary UMOD excretion. In all experiments, changes in urinary UMOD excretion were dissociated from kidney UMOD protein and mRNA levels. Colocalization and ex-vivo studies showed that salt-loading increased intracellular UMOD retention in both WKY and SHRSP. Our study provides novel insights into the interplay among salt, UMOD, and BP. The role of UMOD as a cardiovascular risk marker deserves mechanistic reappraisal and further investigations based on our findings.

Inflammation and salt in young adults: the African-PREDICT study.

PURPOSE: Low-grade inflammation and a diet high in salt are both established risk factors for cardiovascular disease. High potassium (K+) intake was found to counter increase in blood pressure due to high salt intake and may potentially also have protective anti-inflammatory effects. To better understand these interactions under normal physiological conditions, we investigated the relationships between 22 inflammatory mediators with 24-h urinary K+ in young healthy adults stratified by low, medium and high salt intake (salt tertiles). We stratified by ethnicity due to potential salt sensitivity in black populations. METHODS: In 991 healthy black (N = 457) and white (N = 534) adults, aged 20-30 years, with complete data for 24-h urinary sodium and K+, we analysed blood samples for 22 inflammatory mediators. RESULTS: We found no differences in inflammatory mediators between low-, mid- and high-sodium tertiles in either the black or white groups. In multivariable-adjusted regression analyses in white adults, we found only in the lowest salt tertile that K+ associated negatively with pro-inflammatory mediators, namely interferon gamma, interleukin (IL) -7, IL-12, IL-17A, IL-23 and tumour necrosis factor alpha (all p ≤ 0.046). In the black population, we found no independent associations between K+ and any inflammatory mediator. CONCLUSION: In healthy white adults, 24-h urinary K+ associated independently and negatively with specific pro-inflammatory mediators, but only in those with a daily salt intake less than 6.31 g, suggesting K+ to play a protective, anti-inflammatory role in a low-sodium environment. No similar associations were found in young healthy black adults.

Mental wellbeing among people in prison in Scotland: an analysis of repeat cross-sectional surveys.

BACKGROUND: Mental wellbeing among people in prison is poorly studied, despite featuring in many health and justice policies. We aimed to describe for the first time mental wellbeing among an unselected national prison sample. METHODS: Since 2013, the Scottish Prisoner Survey-a biennial survey of people in custody in Scotland-has included the Warwick-Edinburgh mental wellbeing scale (WEMWBS), a 14-item scale with higher scores indicating greater wellbeing. We analysed data from sweeps in 2013 (n = 3158), 2015 (n = 2892) and 2017 (n = 2405) using Student's t-test, ANOVA and multiple linear regression. We also used WEMWBS data from the Scottish Health Survey stratified by age, gender and deprivation to compare with the population at liberty. RESULTS: Mean WEMWBS scores overall were 43.4 in 2013 (SD = 12.2), 41.8 (SD = 11.9) in 2015 and 41.2 (SD = 12.3) in 2017. Mean scores were lower among people on remand and with multiple prison episodes. Age-standardized mean scores were lower among people in prison than their peers at liberty. CONCLUSIONS: Poor mental wellbeing is an important, under-studied facet of the extreme health inequalities associated with imprisonment. These results identify that people on remand or with multiple episodes are particularly disadvantaged and provide a baseline for monitoring impacts of service or policy interventions.

Distinct inflammatory mediator patterns in young black and white adults: The African-predict study.

OBJECTIVE: Inflammatory mediators have been implicated in the early stages of cardiovascular disease development, including hypertension. Since global reports reflect a higher hypertension prevalence in black than white populations, we hypothesise the involvement of specific inflammatory mediators. We therefore compared a detailed range of 22 inflammatory mediators between young black and white adults, and determined the relationship with blood pressure. APPROACH AND RESULTS: We included 1197 adults (20-30 years; 50% black; 52% female) with detailed ambulatory blood pressures. Blood samples were analysed for 22 inflammatory mediators. For pro-inflammatory mediators, the black adults had higher C-reactive protein, interferon-inducible T-cell alpha chemoattractant, macrophage inflammatory protein 3 alpha (all p ≤ 0.008), but lower interferon-gamma, interleukin (IL)-1ß, IL-8, IL-12, IL-17A, and tumour necrosis factor alpha (all p ≤ 0.048). For anti-inflammatory mediators the black group consistently had lower levels (IL-5, IL-10 and IL-13 (all p ≤ 0.012)), resulting in generally higher pro-to-anti-inflammatory ratios in black than white adults (p ≤ 0.001). In mediators with pro- and anti-inflammatory functions, the black group had lower granulocyte-macrophage colony-stimulating factor and IL-6 (both p ≤ 0.010). These patterns were confirmed after adjustment for age, sex and waist circumference, or when stratifying by hypertensive status, sex and socio-economic status. Multi-variable adjusted regression analyses and factor analysis yielded no relationship between inflammatory mediators and blood pressure in this young healthy population. CONCLUSIONS: Black and white ethnic groups each consistently presented with unique inflammatory mediator patterns regardless of blood pressure, sex or social class. No association with blood pressure was seen in either of the groups.

Salt stress in the renal tubules is linked to TAL-specific expression of uromodulin and an upregulation of heat shock genes.

Previously, our comprehensive cardiovascular characterization study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesized at the thick ascending limb of the loop of Henle and is encoded by the Umod gene. Umod-/- mice have significantly lower blood pressure than Umod+/+ mice, are resistant to salt-induced changes in blood pressure, and show a leftward shift in pressure-natriuresis curves reflecting changes of sodium reabsorption. Salt stress triggers transcription factors and genes that alter renal sodium reabsorption. To date there are no studies on renal transcriptome responses to salt stress. Here we aimed use RNA-Seq to delineate salt stress pathways in tubules isolated from Umod+/+ mice (a model of sodium retention) and Umod-/- mice (a model of sodium depletion) ± 300 mosmol sodium chloride ( n = 3 per group). In response to salt stress, the tubules of Umod+/+ mice displayed an upregulation of heat shock transcripts. The greatest changes occurred in the expression of: Hspa1a (Log2 fold change 4.35, P = 2.48 e-12) and Hspa1b (Log2 fold change 4.05, P = 2.48 e-12). This response was absent in tubules of Umod-/- mice. Interestingly, seven of the genes discordantly expressed in the Umod-/- tubules were electrolyte transporters. Our results are the first to show that salt stress in renal tubules alters the transcriptome, increasing the expression of heat shock genes. This direction of effect in Umod+/+ tubules suggest the difference is due to the presence of Umod facilitating greater sodium entry into the tubule cell reflecting a specific response to salt stress.

Role of renal transporters and novel regulatory interactions in the TAL that control blood pressure.

Hypertension (HTN), a major public health issue is currently the leading factor in the global burden of disease, where associated complications account for 9.4 million deaths worldwide every year. Excessive dietary salt intake is among the environmental factors that contribute to HTN, known as salt sensitivity. The heterogeneity of salt sensitivity and the multiple mechanisms that link high salt intake to increases in blood pressure are of upmost importance for therapeutic application. A continual increase in the kidney's reabsorption of sodium (Na+) relies on sequential actions at various segments along the nephron. When the distal segments of the nephron fail to regulate Na+, the effects on Na+ homeostasis are unfavorable. We propose that the specific nephron region where increased active uptake occurs as a result of variations in Na+ reabsorption is at the thick ascending limb of the loop of Henle (TAL). The purpose of this review is to urge the consideration of the TAL as contributing to the pathophysiology of salt-sensitive HTN. Further research in this area will enable development of a therapeutic application for targeted treatment.

Understanding extreme mortality among prisoners: a national cohort study in Scotland using data linkage.

BACKGROUND: Mortality is known to be extremely high among people who have been imprisoned, but there is limited information about the factors that explain this increased risk. METHODS: Standard record linkage methods were used to link Scottish prison records and mortality data for all individuals imprisoned in Scotland for the first time between 1 January 1996 and 31 December 2007. RESULTS: Among 76 627 individuals there were 4414 deaths (3982 in men). When compared with the general population, the age-standardized mortality rate ratio for those imprisoned was 3.3 (95% CI: 3.2, 3.4) for men and 7.6 (6.9, 8.3) for women. Further adjustment for an area measure of deprivation accounted for part but not all of this excess risk [adjusted rate ratio 2.3 (2.2, 2.4) and 5.7 (5.1, 6.2) for men and women, respectively]. Relative risks were highest for drug and alcohol related causes, suicide and homicide and were markedly higher among women than men. Out of prison deaths were most frequent in the first 2 weeks after release from prison. Mortality rates were lower in those with longer total duration in prison and higher in those with multiple short episodes in prison. CONCLUSION: People who have been imprisoned in Scotland experience substantial excess mortality from a range of causes that is only partly explained by deprivation. The association of increased mortality with multiple periods in prison and the concentration of deaths in the early period after prison release both have implications for policy and practice.

Assessing the representativeness of population-sampled health surveys through linkage to administrative data on alcohol-related outcomes.

Health surveys are an important resource for monitoring population health, but selective nonresponse may impede valid inference. This study aimed to assess nonresponse bias in a population-sampled health survey in Scotland, with a focus on alcohol-related outcomes. Nonresponse bias was assessed by examining whether rates of alcohol-related harm (i.e., hospitalization or death) and all-cause mortality among respondents to the Scottish Health Surveys (from 1995 to 2010) were equivalent to those in the general population, and whether the extent of any bias varied according to sociodemographic attributes or over time. Data from consenting respondents (aged 20-64 years) to 6 Scottish Health Surveys were confidentially linked to death and hospitalization records and compared with general population counterparts. Directly age-standardized incidence rates of alcohol-related harm and all-cause mortality were lower among Scottish Health Survey respondents compared with the general population. For all years combined, the survey-to-population rate ratios were 0.69 (95% confidence interval: 0.61, 0.76) for the incidence of alcohol-related harm and 0.89 (95% confidence interval: 0.83, 0.96) for all-cause mortality. Bias was more pronounced among persons residing in more deprived areas; limited evidence was found for regional or temporal variation. This suggests that corresponding underestimation of population rates of alcohol consumption is likely to be socially patterned.

Comparative cytotoxicity of nanosilver in human liver HepG2 and colon Caco2 cells in culture.

The use of silver nanoparticles in food, food contact materials, dietary supplements and cosmetics has increased significantly owing to their antibacterial and antifungal properties. As a consequence, the need for validated rapid screening methods to assess their toxicity is necessary to ensure consumer safety. This study evaluated two widely used in vitro cell culture models, human liver HepG2 cells and human colon Caco2 cells, as tools for assessing the potential cytotoxicity of food- and cosmetic-related nanoparticles. The two cell culture models were utilized to compare the potential cytotoxicity of 20-nm silver. The average size of the silver nanoparticle determined by our transmission electron microscopy (TEM) analysis was 20.4 nm. The dynamic light scattering (DLS) analysis showed no large agglomeration of the silver nanoparticles. The concentration of the 20-nm silver solution determined by our inductively coupled plasma-mass spectrometry (ICP-MS) analysis was 0.962 mg ml(-1) . Our ICP-MS and TEM analysis demonstrated the uptake of 20-nm silver by both HepG2 and Caco2 cells. Cytotoxicity, determined by the Alamar Blue reduction assay, was evaluated in the nanosilver concentration range of 0.1 to 20 µg ml(-1) . Significant concentration-dependent cytotoxicity of the nanosilver in HepG2 cells was observed in the concentration range of 1 to 20 µg ml(-1) and at a higher concentration range of 10 to 20 µg ml(-1) in Caco2 cells compared with the vehicle control. A concentration-dependent decrease in dsDNA content was observed in both cell types exposed to nanosilver but not controls, suggesting an increase in DNA damage. The DNA damage was observed in the concentration range of 1 to 20 µg ml(-1) . Nanosilver-exposed HepG2 and Caco2 cells showed no cellular oxidative stress, determined by the dichlorofluorescein assay, compared with the vehicle control in the concentration range used in this study. A concentration-dependent decrease in mitochondria membrane potential in both nanosilver exposed cell types suggested increased mitochondria injury compared with the vehicle control. The mitochondrial injury in HepG2 cells was significant in the concentration range of 1 to 20 µg ml(-1) , but in Caco2 cells it was significant at a higher concentration range of 10 to 20 µg ml(-1) . These results indicated that HepG2 cells were more sensitive to nanosilver exposure than Caco2 cells. It is generally believed that cellular oxidative stress induces cytotoxicity of nanoparticles. However, in this study we did not detect any nanosilver-induced oxidative stress in either cell type at the concentration range used in this study. Our results suggest that cellular oxidative stress did not play a major role in the observed cytotoxicity of nanosilver in HepG2 and Caco2 cells and that a different mechanism of nanosilver-induced mitochondrial injury leads to the cytotoxicity. The HepG2 and Caco2 cells used this study appear to be targets for silver nanoparticles. The results of this study suggest that the differences in the mechanisms of toxicity induced by nanosilver may be largely as a consequence of the type of cells used. This differential rather than universal response of different cell types exposed to nanoparticles may play an important role in the mechanism of their toxicity. In summary, the results of this study indicate that the widely used in vitro models, HepG2 and Caco2 cells in culture, are excellent systems for screening cytotoxicity of silver nanoparticles. These long established cell culture models and simple assays used in this study can provide useful toxicity and mechanistic information that can help to better inform safety assessments of food- and cosmetic-related silver nanoparticles.

Sex and race differences in urinary Tumor Necrosis Factor-α (TNF-α) levels: Secondary analysis of the DASH-sodium trial.

Previous work in mouse models shows that urinary TNF-α levels become elevated when dietary salt (NaCl) intake increases. To examine if this relationship exists in humans, we conducted a secondary analysis of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial to determine levels of urinary TNF-α in 367 subjects categorized by race, sex, and blood pressure. The DASH-Sodium trial is a multicenter feeding trial in which subjects were randomly assigned to either the DASH or control diet, and high, medium, and low sodium in random order. Multivariable linear regression was used to model baseline TNF-α and a mixed model was used to model TNF-α as a function of dietary intervention. At baseline, with all subjects on a "typical American diet", urinary TNF-α levels were lowest in Black, p = 0.002 and male subjects, p < 0.001. After randomization to either the DASH or control diet, with increasing levels of sodium, urinary TNF-α levels increased only in subjects on the control diet, p < 0.05. As in the baseline analysis, TNF-α levels were highest in White females, then White males, Black females and lowest in Black males. The results indicate that urinary TNF-α levels in DASH-Sodium subjects are regulated by NaCl intake, modulated by the DASH diet, and influenced by both race and sex. The inherent differences between subgroups support studies in mice showing that increases in renal TNF-α minimize the extent salt-dependent activation of NKCC2.

Assessment of alcohol problems using AUDIT in a prison setting: more than an 'aye or no' question.

BACKGROUND: Alcohol problems are a major UK and international public health issue. The prevalence of alcohol problems is markedly higher among prisoners than the general population. However, studies suggest alcohol problems among prisoners are under-detected, under-recorded and under-treated. Identifying offenders with alcohol problems is fundamental to providing high quality healthcare. This paper reports use of the AUDIT screening tool to assess alcohol problems among prisoners. METHODS: Universal screening was undertaken over ten weeks with all entrants to one male Scottish prison using the AUDIT standardised screening tool and supplementary contextual questions. The questionnaire was administered by trained prison officers during routine admission procedures. Overall 259 anonymised completed questionnaires were analysed. RESULTS: AUDIT scores showed a high prevalence of alcohol problems with 73% of prisoner scores indicating an alcohol use disorder (8+), including 36% having scores indicating 'possible dependence' (20-40). AUDIT scores indicating 'possible dependence' were most apparent among 18-24 and 40-64 year-olds (40% and 56% respectively). However, individual questions showed important differences, with younger drinkers less likely to demonstrate habitual and addictive behaviours than the older age group. Disparity between high levels of harmful/hazardous/dependent drinking and low levels of 'treatment' emerged (only 27% of prisoners with scores indicating 'possible dependence' reported being 'in treatment'). Self-reported associations between drinking alcohol and the index crime were identified among two-fifths of respondents, rising to half of those reporting violent crimes. CONCLUSIONS: To our knowledge, this is the first study to identify differing behaviours and needs among prisoners with high AUDIT score ranges, through additional analysis of individual questions. The study has identified high prevalence of alcohol use, varied problem behaviours, and links across drinking, crime and recidivism, supporting the argument for more extensive provision of alcohol-focused interventions in prisons. These should be carefully targeted based on initial screening and assessment, responsive, and include care pathways linking prisoners to community services. Finally, findings confirm the value and feasibility of routine use of the AUDIT screening tool in prison settings, to considerably enhance practice in the detection and understanding of alcohol problems, improving on current more limited questioning (e.g. 'yes or no' questions).

Evaluation of a national smoke-free prisons policy using medication dispensing: an interrupted time-series analysis.

BACKGROUND: Internationally, smoking prevalence among people in prison custody (ie, people on remand awaiting trial, awaiting sentencing, or serving a custodial sentence) is high. In Scotland, all prisons implemented a comprehensive smoke-free policy in 2018 after a 16-month anticipatory period. In this study, we aimed to use data on medication dispensing to assess the impact of this policy on cessation support, health outcomes, and potential unintended consequences among people in prison custody. METHODS: We did an interrupted time-series analysis using dispensing data for 44 660 individuals incarcerated in 14 closed prisons in Scotland between March 30, 2014, and Nov 30, 2019. We estimated changes in dispensing rates associated with the policy announcement (July 17, 2017) and full implementation (Nov 30, 2018) using seasonal autoregressive integrated moving average models. Medication categories of primary interest were treatments for nicotine dependence (as an indicator of smoking cessation or abstinence attempts), acute smoking-associated illnesses, and mental health (antidepressants). We included antiepileptic medications as a negative control. FINDINGS: A 44% step increase in dispensing of treatments for nicotine dependence was observed at implementation (2250 items per 1000 people in custody per fortnight, 95% CI 1875 to 2624) due primarily to a 42% increase in dispensing of nicotine replacement therapy (2109 items per 1000 people in custody per fortnight, 1701 to 2516). A 9% step decrease in dispensing for smoking-related illnesses was observed at implementation, largely accounted for by respiratory medications (-646 items per 1000 people in custody per fortnight, -1111 to -181). No changes associated with announcement or implementation were observed for mental health dispensing or antiepileptic medications (control). INTERPRETATION: Smoke-free prison policies might improve respiratory health among people in custody and encourage smoking abstinence or cessation without apparent short-term adverse effects on mental health dispensing. FUNDING: National Institute of Health Research Public Health Research programme, Scottish Government Chief Scientist Office, and UK Medical Research Council.

The scar on the face of Scotland: deprivation and alcohol-related facial injuries in Scotland.

BACKGROUND: : Recent media and political attention have focused on a "rising tide" of youth violence and alcohol-related problems in Scotland. Facial injuries in Scotland are most commonly sustained as a result of interpersonal violence, and young men are a high risk group for facial injuries. Facial injuries are known to be associated with alcohol consumption but the sociodemographic determinants are not fully known. METHODS: : Influences on the incidence of alcohol-related facial injuries were investigated using data on 22,417 patients between 2001 and 2006 from the Scottish Morbidity Records. RESULTS: : Since 2001, the incidence of alcohol-related facial injuries in Scotland has declined, but the nature and scale of the problem remain considerable, with the major burden for such injuries disproportionately affecting young men from socioeconomically deprived areas. CONCLUSIONS: : The role of poverty as the major determinant of alcohol-related facial injuries has thus far not been explicitly acknowledged. Interventions to change behavior alone are unlikely to succeed unless they are supported by measures designed to improve socioeconomic circumstances and to reduce socioeconomic inequalities.

Inflammation and hypertension development: A longitudinal analysis of the African-PREDICT study.

BACKGROUND: The role of inflammation in the development of hypertension remains incompletely understood. While single inflammatory mediators have been shown to associate with changes in blood pressure (ΔBP), the role of clusters of inflammatory mediators has been less comprehensively explored. We therefore determined whether individual or clusters of inflammatory mediators from a large biomarker panel were associated with ΔBP over 4.5 years, in young healthy adults. METHODS: We included 358 adults (white, n = 156; black, n = 202) with detailed information on ambulatory blood pressure (BP) at baseline and follow-up. Baseline blood samples were analysed for 22 inflammatory mediators using multiplexing technology. Principal component analysis was used to study associations between clusters of inflammatory mediators and ΔBP. RESULTS: In the total cohort in multivariable-adjusted regression analyses, percentage change in 24hr systolic BP associated positively with Factors 1 (Interferon-gamma, interleukin (IL)-4, IL-7, IL-10, IL-12, IL-17A, IL-21, IL-23, macrophage inflammatory protein (MIP)-1α, MIP-1ß, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF)) and 2 (IL-5, IL-6, IL-8, IL-13). Change in daytime systolic BP associated positively with Factors 1, 2 and 3 (C-Reactive protein, IL-1ß, IL-2, MIP-3α). Subgroup analysis found these findings were limited to white study participants. Numerous associations were present between individual inflammatory mediators (Interferon-gamma, GM-CSF, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-21, IL-23, MIP-1α and MIP-1ß) and ΔBP in the white but not black subgroups. CONCLUSION: We found independent relationships between numerous inflammatory mediators (individual and clusters) and ΔBP over 4.5 years. The relationship between inflammatory markers and ΔBP was only found in white participants. ClinicalTrials.gov (Identifier: NCT03292094)..

A population-based record linkage study of mortality in hepatitis C-diagnosed persons with or without HIV coinfection in Scotland.

Infection with the hepatitis C virus (HCV) is known to increase the risk of death from severe liver disease and, because HCV status is strongly associated with a history of injecting drug use, the effect of a key disease progression cofactor, infection with human immunodeficiency virus (HIV), is of interest. We examined all-cause, liver-related and drug-related mortality and excess risk of death from these causes in a large cohort of HCV-monoinfected and HIV-coinfected persons in Scotland. The study population consisted of 20,163 persons confirmed to be infected with hepatitis C through laboratory testing in Scotland between 1991 and 2005. Records with sufficient identifiers were linked to the General Register Office for Scotland death register to retrieve associated mortality data, and were further linked to a national database of HIV-positive individuals to determine coinfection status. A total of 1715 HCV monoinfected and 305 HIV coinfected persons died of any cause during the follow-up period (mean of 5.4 and 6.4 years, respectively). Significant excess mortality was observed in both HCV monoinfected and HIV coinfected populations from liver-related underlying causes (standardised mortality ratios of 25, 95% CI = 23-27; and 37, 95% CI = 26-52 for the two groups, respectively) and drug-related causes (25, 95% CI = 23-27; 39, 95% CI = 28-53. The risk of death from hepatocellular carcinoma, alcoholic or non-alcoholic liver disease, or from a drug-related cause, was greatly increased compared with the general Scottish population, with the highest standardised mortality ratio observed for hepatocellular carcinoma in the monoinfected group (70, 95% CI = 57-85). This study has revealed considerable excess mortality from liver- and drug-related causes in the Scottish HCV-diagnosed population; these data are crucial to inform on the clinical management, and projected future public health burden, of HCV infection.

Evaluating possible intended and unintended consequences of the implementation of alcohol minimum unit pricing (MUP) in Scotland: a natural experiment protocol.

INTRODUCTION: Scotland is the first country to carry out a national implementation of minimum unit pricing (MUP) for alcohol. MUP aims to reduce alcohol-related harms, which are high in Scotland compared with Western Europe, and to improve health equalities. MUP is a minimum retail price per unit of alcohol. That approach targets high-risk alcohol users. This work is key to a wider evaluation that will determine whether MUP continues. There are three study components. METHODS AND ANALYSIS: Component 1 sampled an estimated 2800 interviewees at a baseline and each of two follow-ups from four Emergency Departments in Scotland and Northern England. Research nurses administered a standardised survey to assess alcohol consumption and the proportion of attendances that were alcohol-related.Component 2 covered six Sexual Health Clinics with similar timings and country allocation. A self-completion survey gathered information on potential unintended effects of MUP on alcohol source and drug use.Using a natural experiment design and repeated cross-sectional audit, difference between Scotland (intervention) and North England (control) will be tested for outcomes using regression adjusting for differences at baseline. Differential impacts by age, gender and socioeconomic position will be investigated.Component 3 used focus groups with young people and heavy drinkers and interviews with stakeholders before and after MUP implementation. The focus groups will allow exploration of attitudes, experiences and behaviours and the potential mechanisms by which impacts arise. The interviews will help characterise the implementation process. ETHICS AND DISSEMINATION: Study components 1 and 2 have been ethically approved by the NHS, and component 3 by the University of Stirling. Dissemination plans include peer-reviewed journal articles, presentations, policy maker briefings and, in view of high public interest and the high political profile of this flagship policy, communication with the public via media engagement and plain language summaries. TRIAL REGISTRATION NUMBER: ISRCTN16039407; Pre-results.

Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) - a natural experiment (protocol).

INTRODUCTION: Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV 'Treatment as Prevention' (TasP) in PWID. METHODS AND ANALYSIS: We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome - chronic HCV prevalence in PWID - is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a 'virtual cohort' of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes. ETHICS AND DISSEMINATION: Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.

Do patients who die from an alcohol-related condition 'drift' into areas of greater deprivation? Alcohol-related mortality and health selection theory in Scotland.

BACKGROUND: Health selection has been proposed to explain the patterning of alcohol-related mortality by area deprivation. This study investigated whether persons who die from alcohol-related conditions are more likely to experience social drift than those who die from other causes. METHODS: Deaths recorded in Scotland (2013, >21 years) were coded as 'alcohol-related' or 'other' and by deprivation decile of residence at death. Acute hospital admissions data from 1996 to 2012 were used to provide premortality deprivation data. χ² tests estimated the difference between observed and expected alcohol-related deaths by first Scottish Index of Multiple Deprivation (SIMD) decile and type of death. Logistic regression models were fitted using type of death as the outcome of interest and change in SIMD decile as the exposure of interest. RESULTS: Of 47 012 deaths, 1458 were alcohol-related. Upward and downward mobility was observed for both types of death. An estimated 31 more deaths than expected were classified 'alcohol-related' among cases whose deprivation score decreased, while 204 more deaths than expected were classified 'alcohol-related' among cases whose initial deprivation ranking was in the four most deprived deciles. Becoming more deprived and first deprivation category were both associated with increased odds of type of death being alcohol-related after adjusting for confounders. CONCLUSION: This study suggests that health selection appears to contribute less to the deprivation gradient in alcohol-related mortality in Scotland than an individual's initial area deprivation category.

Adjustment for survey non-representativeness using record-linkage: refined estimates of alcohol consumption by deprivation in Scotland.

BACKGROUND AND AIMS: Analytical approaches to addressing survey non-participation bias typically use only demographic information to improve estimates. We applied a novel methodology which uses health information from data linkage to adjust for non-representativeness. We illustrate the method by presenting adjusted alcohol consumption estimates for Scotland. DESIGN: Data on consenting respondents to the Scottish Health Surveys (SHeSs) 1995-2010 were linked confidentially to routinely collected hospital admission and mortality records. Synthetic observations representing non-respondents were created using general population data. Multiple imputation was performed to compute adjusted alcohol estimates given a range of assumptions about the missing data. Adjusted estimates of mean weekly consumption were additionally calibrated to per-capita alcohol sales data. SETTING: Scotland. PARTICIPANTS: 13 936 male and 18 021 female respondents to the SHeSs 1995-2010, aged 20-64 years. MEASUREMENTS: Weekly alcohol consumption, non-, binge- and problem-drinking. FINDINGS: Initial adjustment for non-response resulted in estimates of mean weekly consumption that were elevated by up to 17.8% [26.5 units (18.6-34.4)] compared with corrections based solely on socio-demographic data [22.5 (17.7-27.3)]; other drinking behaviour estimates were little changed. Under more extreme assumptions the overall difference was up to 53%, and calibrating to sales estimates resulted in up to 88% difference. Increases were especially pronounced among males in deprived areas. CONCLUSIONS: The use of routinely collected health data to reduce bias arising from survey non-response resulted in higher alcohol consumption estimates among working-age males in Scotland, with less impact for females. This new method of bias reduction can be generalized to other surveys to improve estimates of alternative harmful behaviours.