Relation of severe COVID-19 to polypharmacy and prescribing of psychotropic drugs: the REACT-SCOT case-control study.

BACKGROUND: The objective of this study was to investigate the relation of severe COVID-19 to prior drug prescribing. METHODS: Severe cases were defined by entry to critical care or fatal outcome. For this matched case-control study (REACT-SCOT), all 4251 cases of severe COVID-19 in Scotland since the start of the epidemic were matched for age, sex and primary care practice to 36,738 controls from the population register. Records were linked to hospital discharges since June 2015 and dispensed prescriptions issued in primary care during the last 240 days. RESULTS: Severe COVID-19 was strongly associated with the number of non-cardiovascular drug classes dispensed. This association was strongest in those not resident in a care home, in whom the rate ratio (95% CI) associated with dispensing of 12 or more drug classes versus none was 10.8 (8.8, 13.3), and in those without any of the conditions designated as conferring increased risk of COVID-19. Of 17 drug classes postulated at the start of the epidemic to be "medications compromising COVID", all were associated with increased risk of severe COVID-19 and these associations were present in those without any of the designated risk conditions. The fraction of cases in the population attributable to exposure to these drug classes was 38%. The largest effect was for antipsychotic agents: rate ratio 4.18 (3.42, 5.11). Other drug classes with large effects included proton pump inhibitors (rate ratio 2.20 (1.72, 2.83) for = 2 defined daily doses/day), opioids (3.66 (2.68, 5.01) for = 50 mg morphine equivalent/day) and gabapentinoids. These associations persisted after adjusting for covariates and were stronger with recent than with non-recent exposure. CONCLUSIONS: Severe COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression, or dyskinesia; have anticholinergic effects; or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. Measures to reduce the burden of mortality and morbidity from COVID-19 should include reinforcing existing guidance on reducing overprescribing of these drug classes and limiting inappropriate polypharmacy. REGISTRATION: ENCEPP number EUPAS35558.

Population impact of direct-acting antiviral treatment on new presentations of hepatitis C-related decompensated cirrhosis: a national record-linkage study.

OBJECTIVE: Population-based studies demonstrating the clinical impact of interferon-free direct-acting antiviral (DAA) therapies are lacking. We examined the impact of the introduction of DAAs on HCV-related decompensated cirrhosis (DC) through analysis of population-based data from Scotland. DESIGN: Through analysis of national surveillance data (involving linkage of HCV diagnosis and clinical databases to hospital and deaths registers), we determined i) the scale-up in the number of patients treated and achieving a sustained viral response (SVR), and ii) the change in the trend of new presentations with HCV-related DC, with the introduction of DAAs. RESULTS: Approximately 11 000 patients had been treated in Scotland over the 8-year period 2010/11 to 2017/18. The scale-up in the number of patients achieving SVR between the pre-DAA and DAA eras was 2.3-fold overall and 5.9-fold among those with compensated cirrhosis (the group at immediate risk of developing DC). In the pre-DAA era, the annual number of HCV-related DC presentations increased 4.6-fold between 2000 (30) and 2014 (142). In the DAA era, presentations decreased by 51% to 69 in 2018 (and by 67% among those with chronic infection at presentation), representing a significant change in trend (rate ratio 0.88, 95% CI 0.85 to 0.90). With the introduction of DAAs, an estimated 330 DC cases had been averted during 2015-18. CONCLUSIONS: National scale-up in interferon-free DAA treatment is associated with the rapid downturn in presentations of HCV-related DC at the population-level. Major progress in averting HCV-related DC in the short-term is feasible, and thus other countries should strive to achieve the same.

Rapid Epidemiological Analysis of Comorbidities and Treatments as risk factors for COVID-19 in Scotland (REACT-SCOT): A population-based case-control study.

BACKGROUND: The objectives of this study were to identify risk factors for severe coronavirus disease 2019 (COVID-19) and to lay the basis for risk stratification based on demographic data and health records. METHODS AND FINDINGS: The design was a matched case-control study. Severe COVID-19 was defined as either a positive nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the national database followed by entry to a critical care unit or death within 28 days or a death certificate with COVID-19 as underlying cause. Up to 10 controls per case matched for sex, age, and primary care practice were selected from the national population register. For this analysis-based on ascertainment of positive test results up to 6 June 2020, entry to critical care up to 14 June 2020, and deaths registered up to 14 June 2020-there were 36,948 controls and 4,272 cases, of which 1,894 (44%) were care home residents. All diagnostic codes from the past 5 years of hospitalisation records and all drug codes from prescriptions dispensed during the past 240 days were extracted. Rate ratios for severe COVID-19 were estimated by conditional logistic regression. In a logistic regression using the age-sex distribution of the national population, the odds ratios for severe disease were 2.87 for a 10-year increase in age and 1.63 for male sex. In the case-control analysis, the strongest risk factor was residence in a care home, with rate ratio 21.4 (95% CI 19.1-23.9, p = 8 × 10-644). Univariate rate ratios for conditions listed by public health agencies as conferring high risk were 2.75 (95% CI 1.96-3.88, p = 6 × 10-9) for type 1 diabetes, 1.60 (95% CI 1.48-1.74, p = 8 × 10-30) for type 2 diabetes, 1.49 (95% CI 1.37-1.61, p = 3 × 10-21) for ischemic heart disease, 2.23 (95% CI 2.08-2.39, p = 4 × 10-109) for other heart disease, 1.96 (95% CI 1.83-2.10, p = 2 × 10-78) for chronic lower respiratory tract disease, 4.06 (95% CI 3.15-5.23, p = 3 × 10-27) for chronic kidney disease, 5.4 (95% CI 4.9-5.8, p = 1 × 10-354) for neurological disease, 3.61 (95% CI 2.60-5.00, p = 2 × 10-14) for chronic liver disease, and 2.66 (95% CI 1.86-3.79, p = 7 × 10-8) for immune deficiency or suppression. Seventy-eight percent of cases and 52% of controls had at least one listed condition (51% of cases and 11% of controls under age 40). Severe disease was associated with encashment of at least one prescription in the past 9 months and with at least one hospital admission in the past 5 years (rate ratios 3.10 [95% CI 2.59-3.71] and 2.75 [95% CI 2.53-2.99], respectively) even after adjusting for the listed conditions. In those without listed conditions, significant associations with severe disease were seen across many hospital diagnoses and drug categories. Age and sex provided 2.58 bits of information for discrimination. A model based on demographic variables, listed conditions, hospital diagnoses, and prescriptions provided an additional 1.07 bits (C-statistic 0.804). A limitation of this study is that records from primary care were not available. CONCLUSIONS: We have shown that, along with older age and male sex, severe COVID-19 is strongly associated with past medical history across all age groups. Many comorbidities beyond the risk conditions designated by public health agencies contribute to this. A risk classifier that uses all the information available in health records, rather than only a limited set of conditions, will more accurately discriminate between low-risk and high-risk individuals who may require shielding until the epidemic is over.

Hepatitis C test uptake among historic blood transfusion recipients following media coverage of the Penrose Inquiry and an awareness-raising campaign.

The final report of the Penrose Inquiry into historic transmission of HIV and hepatitis C (HCV) through blood transfusion/products in Scotland was published in March 2015 and recommended "everyone who had received a blood transfusion prior to 1991 and who had not had a test for HCV should be offered one." A targeted awareness-raising campaign to encourage such individuals to be tested was launched in October 2016. We examined HCV testing undertaken in 2015-2016 in three NHS boards in Scotland to evaluate impact of these events. Statistical process control was used to monitor trends in individuals tested and those mentioning transfusion. HCV positivity was calculated and multivariate logistic regression was used to examine factors associated with mention of transfusion. A total of 22 842 individuals received an HCV test in 2015-2016 and 3% of those with clinical information mentioned transfusion. The total number of HCV tests was significantly higher in the week following the Penrose Report and the number mentioning transfusion was significantly higher for three weeks. There was no significant increase following the awareness-raising campaign. Women and those aged over 50 years were the most likely to have mentioned transfusion. Overall HCV positivity was 3.7% and <1% for the transfusion group. The impact of both intense media coverage and the government-funded awareness-raising campaigns in terms of HCV test uptake was modest and short-lived. Our findings highlight the challenges of case-finding for HCV and the limited impact of awareness-raising. This can be used by other countries aiming to identify those infected through historic blood transfusion.

A pragmatic harm reduction approach to manage a large outbreak of wound botulism in people who inject drugs, Scotland 2015.

BACKGROUND: People who inject drugs (PWID) are at an increased risk of wound botulism, a potentially fatal acute paralytic illness. During the first 6 months of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland, which resulted in the largest outbreak in Europe to date. METHODS: A multidisciplinary Incident Management Team (IMT) was convened to conduct an outbreak investigation, which consisted of enhanced surveillance of cases in order to characterise risk factors and identify potential sources of infection. RESULTS: Between the 24th of December 2014 and the 30th of May 2015, a total of 40 cases were reported across six regions in Scotland. The majority of the cases were male, over 30 and residents in Glasgow. All epidemiological evidence suggested a contaminated batch of heroin or cutting agent as the source of the outbreak. There are significant challenges associated with managing an outbreak among PWID, given their vulnerability and complex addiction needs. Thus, a pragmatic harm reduction approach was adopted which focused on reducing the risk of infection for those who continued to inject and limited consequences for those who got infected. CONCLUSIONS: The management of this outbreak highlighted the importance and need for pragmatic harm reduction interventions which support the addiction needs of PWID during an outbreak of spore-forming bacteria. Given the scale of this outbreak, the experimental learning gained during this and similar outbreaks involving spore-forming bacteria in the UK was collated into national guidance to improve the management and investigation of future outbreaks among PWID.

Liver mortality attributable to chronic hepatitis C virus infection in Denmark and Scotland--using spontaneous resolvers as the benchmark comparator.

UNLABELLED: Liver mortality among individuals with chronic hepatitis C (CHC) infection is common, but the relative contribution of CHC per se versus adverse health behaviors is uncertain. We explored data on spontaneous resolvers of hepatitis C virus (HCV) as a benchmark group to uncover the independent contribution of CHC on liver mortality. Using national HCV diagnosis and mortality registers from Denmark and Scotland, we calculated the liver mortality rate (LMR) for persons diagnosed with CHC infection (LMRchronic ) and spontaneously resolved infection (LMRresolved ), according to subgroups defined by age, sex, and drug use. Through these mortality rates, we determined subgroup-specific attributable fractions (AFs), defined as (LMRchronic - LMRresolved )/LMRchronic , and then calculated the total attributable fraction (TAF) as a weighted average of these AFs. Thus, the TAF represents the overall fraction (where 0.00 = not attributable at all; and 1.00 = entirely attributable) of liver mortality attributable to CHC in the diagnosed population. Our cohort comprised 7,005 and 21,729 persons diagnosed with HCV antibodies in Denmark and Scotland, respectively. Mean follow-up duration was 6.3-6.9 years. The TAF increased stepwise with age. It was lowest for death occurring at <45 years of age (0.21 in Denmark; 0.26 in Scotland), higher for death occurring at 45-59 years (0.69 in Denmark; 0.69 in Scotland), and highest for death at 60+years (0.92 in Denmark; 0.75 in Scotland). Overall, the TAF was 0.66 (95% confidence interval [CI]: 0.55-0.78) in Denmark and 0.55 (95% CI: 0.44-0.66) in Scotland. CONCLUSIONS: In Denmark and Scotland, the majority of liver death in the CHC-diagnosed population can be attributed to CHC-nevertheless, an appreciable fraction cannot, cautioning that liver mortality in this population is a compound problem that can be reduced, but not solved, through antiviral therapy alone.

HCV epidemiology in high-risk groups and the risk of reinfection.

Injecting risk behaviours among people who inject drugs (PWID) and high-risk sexual practices among men who have sex with men (MSM) are important routes of hepatitis C virus (HCV) transmission. Current direct-acting antiviral treatment offers unique opportunities for reductions in HCV-related liver disease burden and epidemic control in high-risk groups, but these prospects could be counteracted by HCV reinfection due to on-going risk behaviours after successful treatment. Based on existing data from small and heterogeneous studies of interferon-based treatment, the incidence of reinfection after sustained virological response range from 2-6/100 person years among PWID to 10-15/100 person years among human immunodeficiency virus-infected MSM. These differences mainly reflect heterogeneity in study populations with regards to risk behaviours, but also reflect variations in study designs and applied virological methods. Increasing levels of reinfection are to be expected as we enter the interferon-free treatment era. Individual- and population-level efforts to address and prevent reinfection should therefore be undertaken when providing HCV care for people with on-going risk behaviour. Constructive strategies include acknowledgement, education and counselling, harm reduction optimization, scaled-up treatment including treatment of injecting networks, post-treatment screening, and rapid retreatment of reinfections.

Assessing the cost-effectiveness of treating chronic hepatitis C virus in people who inject drugs in Australia.

BACKGROUND AND AIM: To assess the cost-effectiveness of hepatitis C virus treatment with pegylated interferon alfa-2a and ribavirin in current and former people who inject drugs (PWID). METHODS: A decision analytic model simulated the lifetime costs and outcomes of four treatment options: early treatment with mild fibrosis, standard treatment with moderate fibrosis, late treatment with compensated cirrhosis, and no treatment. Treatment modalities were simulated across current, former, and never-injector cohorts of 1000 hypothetical patients with chronic hepatitis C virus. The main outcome measures were incremental costs ($AUD) per quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICERs) were calculated for each cohort. RESULTS: Treatment of current PWID during mild fibrosis resulted in a discounted average gain of 1.60 QALYs (95% confidence interval 0.93-2.26) for an added cost of $12,723 ($11,153-$14,396) compared with no treatment, yielding an ICER of $7941 per QALY gained ($6347-$12,017). Former PWID gained 1.80 QALYs (1.29-2.33) for $10,441 ($8843-$12,074) for early treatment compared with no treatment, resulting in an ICER of $5808 per QALY gained ($5189-$6849). Never-injectors gained 2.33 QALYs (1.87-2.80) for $9290 ($7642-$10,912) compared with no treatment-an ICER of $3985 per QALY gained ($3896-$4080). Early treatment was more cost-effective than late treatment in all cohorts. CONCLUSIONS: Despite comorbidities, increased mortality, and reduced adherence, treatment of both current and former PWID is cost-effective. Our estimates fall below the unofficial Australian cost-effectiveness threshold of $AUD 50,000 per QALY for public subsidies. Scaling up treatment for PWID can be justified on purely economic grounds.

Using a Brief Intervention to Improve Partner-Focused Conversation in Adolescents with Autism.

Individuals on the autism spectrum often experience pragmatic social conversation difficulties that include showing interest in their conversational partners. This may become particularly evident during adolescence when conversation with peers is the primary medium for social interaction. This study used a multiple baseline design across participants to investigate the effects of a brief intervention package on the partner-focused conversation of three adolescents with autism. Results showed increased partner-focused questions and comments for all participants. Social validity assessments indicated that the intervention led to meaningful improvements in peer conversations.

Trends in the incidence of HIV in Scotland, 1988-2009.

OBJECTIVES: To estimate temporal trends in HIV incidence and prevalence in Scotland, according to three main risk groups for infection: men who have sex with men (MSM), injecting drug users (IDUs) and heterosexuals. METHODS: The authors extracted data for all single- and multiple-tested individuals from the national HIV test database covering the period 1980-2009 and calculated the incidence of HIV infection in each risk group and estimated RRs by fitting Poisson regression models. RESULTS: 620 of 59,807 individuals tested positive following an initial negative HIV test, generating an overall incidence rate of 3.7/1000 person-years (95% CI 3.4 to 4.0); 60%, 20% and 37% of the 620 were associated with the risk behaviour categories MSM, IDU and heterosexual, respectively. The incidence rate among MSM in Scotland remained relatively stable between the periods <1995 and 2005-2009 (overall: 15.3/1000 person-years, 95% CI 13.8 to 17.0), whereas the incidence among IDUs decreased between the periods <1995 and 2005-2009, from 5.1/1000 to 1.7/1000 person-years, and also decreased among heterosexuals, from 2.9/1000 to 1.4/1000 person-years. CONCLUSIONS: The reduction in the incidence rate among IDUs suggests that harm reduction measures initiated from the late 1980s were effective in reducing HIV transmission in this risk group; however, the absence of a reduction in HIV incidence rates among MSM is disappointing and highlights the need for renewed efforts in the prevention of HIV in this major risk group.

Epidemiology of SARS-CoV-2 during the first three waves in Scotland: a national record linkage study.

BACKGROUND: The early COVID-19 pandemic in Scotland-defined as the era before widespread access to vaccination and monoclonal antibody treatment-can be characterised into three distinct waves: March-July 2020, July 2020-April 2021 and May-August 2021. Each wave was met with various societal restrictions in an effort to reduce disease transmission and associated morbidity and mortality. Understanding the epidemiology of infections during these waves can provide valuable insights into future pandemic planning. METHODS: Scottish RT-PCR testing data reported up until 8 August 2021, the day prior to most restrictions being lifted in Scotland, were included. Demographic characteristics including age, sex and social deprivation associated with transmission, morbidity and mortality were compared across waves. A case-control analysis for each wave was then modelled to further compare risk factors associated with death over time. RESULTS: Of the 349 904 reported cases, there were 18 099, 197 251 and 134 554 in waves 1, 2 and 3, respectively. Hospitalisations, intensive care unit admissions and deaths appeared highest in wave 2, though risk factors associated with COVID-19 death remained similar across the waves. Higher deprivation and certain comorbidities were associated with higher deaths in all waves. CONCLUSIONS: Despite the higher number of cases reported in waves 2 and 3, case fatality rates were lower: likely a combination of improved detection of infections in younger age groups, introduction of social measures and vaccination. Higher social deprivation and comorbidities resulted in higher deaths for all waves.

Using Peer Supports to Encourage Adolescents With Autism Spectrum Disorder to Show Interest in Their Conversation Partners.

PURPOSE: This study was conducted to evaluate the effects of a multicomponent peer-mediated intervention (PMI) on teaching adolescents with autism spectrum disorder (ASD) how to show interest in peer conversation partners by asking partner-focused questions about the person, their interests, or their experiences and by making partner-focused comments that positively affirm peer statements or express concern. METHOD: A multiple-baseline design across three verbally fluent high school students with ASD was used to assess the effects of the PMI, which involved training peers (n = 10) to support conversation and the students' use of target skills, and training the students to use partner-focused skills with the aid of a self-reflection cue sheet during conversation with trained peers in a high school cafeteria. Ten-minute samples of student-peer conversations were transcribed and analyzed. Generalization with untrained peers was assessed. RESULTS: The PMI was highly effective in increasing all students' use of partner-focused skills. Gains were maintained by two students in a return-to-baseline condition. Generalization was evident for all students with varied results. Peers and students with ASD perceived the intervention to be beneficial. CONCLUSIONS: This study adds to the limited research showing that PMI can be used in high school settings to improve target conversational skills and provides preliminary evidence that PMI can successfully address an underresearched pragmatic language difficulty (i.e., introducing and maintaining topics of conversation of relevance and interest to conversation partners) common among adolescents with ASD. These findings invite replication to extend generality and assess the impact of the intervention on peer relationships. Supplemental Material https://doi.org/10.23641/asha.16915663.

Risks of and risk factors for COVID-19 disease in people with diabetes: a cohort study of the total population of Scotland.

BACKGROUND: We aimed to ascertain the cumulative risk of fatal or critical care unit-treated COVID-19 in people with diabetes and compare it with that of people without diabetes, and to investigate risk factors for and build a cross-validated predictive model of fatal or critical care unit-treated COVID-19 among people with diabetes. METHODS: In this cohort study, we captured the data encompassing the first wave of the pandemic in Scotland, from March 1, 2020, when the first case was identified, to July 31, 2020, when infection rates had dropped sufficiently that shielding measures were officially terminated. The participants were the total population of Scotland, including all people with diabetes who were alive 3 weeks before the start of the pandemic in Scotland (estimated Feb 7, 2020). We ascertained how many people developed fatal or critical care unit-treated COVID-19 in this period from the Electronic Communication of Surveillance in Scotland database (on virology), the RAPID database of daily hospitalisations, the Scottish Morbidity Records-01 of hospital discharges, the National Records of Scotland death registrations data, and the Scottish Intensive Care Society and Audit Group database (on critical care). Among people with fatal or critical care unit-treated COVID-19, diabetes status was ascertained by linkage to the national diabetes register, Scottish Care Information Diabetes. We compared the cumulative incidence of fatal or critical care unit-treated COVID-19 in people with and without diabetes using logistic regression. For people with diabetes, we obtained data on potential risk factors for fatal or critical care unit-treated COVID-19 from the national diabetes register and other linked health administrative databases. We tested the association of these factors with fatal or critical care unit-treated COVID-19 in people with diabetes, and constructed a prediction model using stepwise regression and 20-fold cross-validation. FINDINGS: Of the total Scottish population on March 1, 2020 (n=5 463 300), the population with diabetes was 319 349 (5·8%), 1082 (0·3%) of whom developed fatal or critical care unit-treated COVID-19 by July 31, 2020, of whom 972 (89·8%) were aged 60 years or older. In the population without diabetes, 4081 (0·1%) of 5 143 951 people developed fatal or critical care unit-treated COVID-19. As of July 31, the overall odds ratio (OR) for diabetes, adjusted for age and sex, was 1·395 (95% CI 1·304-1·494; p<0·0001, compared with the risk in those without diabetes. The OR was 2·396 (1·815-3·163; p<0·0001) in type 1 diabetes and 1·369 (1·276-1·468; p<0·0001) in type 2 diabetes. Among people with diabetes, adjusted for age, sex, and diabetes duration and type, those who developed fatal or critical care unit-treated COVID-19 were more likely to be male, live in residential care or a more deprived area, have a COVID-19 risk condition, retinopathy, reduced renal function, or worse glycaemic control, have had a diabetic ketoacidosis or hypoglycaemia hospitalisation in the past 5 years, be on more anti-diabetic and other medication (all p<0·0001), and have been a smoker (p=0·0011). The cross-validated predictive model of fatal or critical care unit-treated COVID-19 in people with diabetes had a C-statistic of 0·85 (0·83-0·86). INTERPRETATION: Overall risks of fatal or critical care unit-treated COVID-19 were substantially elevated in those with type 1 and type 2 diabetes compared with the background population. The risk of fatal or critical care unit-treated COVID-19, and therefore the need for special protective measures, varies widely among those with diabetes but can be predicted reasonably well using previous clinical history. FUNDING: None.

Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study.

OBJECTIVE: To assess the risk of hospital admission for coronavirus disease 2019 (covid-19) among patient facing and non-patient facing healthcare workers and their household members. DESIGN: Nationwide linkage cohort study. SETTING: Scotland, UK, 1 March to 6 June 2020. PARTICIPANTS: Healthcare workers aged 18-65 years, their households, and other members of the general population. MAIN OUTCOME MEASURE: Admission to hospital with covid-19. RESULTS: The cohort comprised 158 445 healthcare workers, most of them (90 733; 57.3%) being patient facing, and 229 905 household members. Of all hospital admissions for covid-19 in the working age population (18-65 year olds), 17.2% (360/2097) were in healthcare workers or their households. After adjustment for age, sex, ethnicity, socioeconomic deprivation, and comorbidity, the risk of admission due to covid-19 in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazard ratio 0.81 (95% confidence interval 0.52 to 1.26) and 0.86 (0.49 to 1.51), respectively). In models adjusting for the same covariates, however, patient facing healthcare workers, compared with non-patient facing healthcare workers, were at higher risk (hazard ratio 3.30, 2.13 to 5.13), as were household members of patient facing healthcare workers (1.79, 1.10 to 2.91). After sub-division of patient facing healthcare workers into those who worked in "front door," intensive care, and non-intensive care aerosol generating settings and other, those in front door roles were at higher risk (hazard ratio 2.09, 1.49 to 2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of hospital admission with covid-19 was less than 0.5%, but it was 1% and above in older men with comorbidity. CONCLUSIONS: Healthcare workers and their households contributed a sixth of covid-19 cases admitted to hospital. Although the absolute risk of admission was low overall, patient facing healthcare workers and their household members had threefold and twofold increased risks of admission with covid-19.

The impact and effectiveness of pneumococcal vaccination in Scotland for those aged 65 and over during winter 2003/2004.

BACKGROUND: For winter 2003/2004 in Scotland, it was recommended that all those aged 65 and over be eligible to receive 23-valent polysaccharide pneumococcal vaccine (23vPPV), which has been shown to be effective in reducing the risk of invasive pneumococcal disease (IPD). We assessed the success of the vaccination programme by examining the age specific incidence rates of IPD compared to four previous winter seasons and estimating vaccination effectiveness. METHODS: Winter season incidence rates of IPD for vaccine targeted (65 years and over) and non-targeted (0-4, 5-34, 35-49, 50-64) age bands were examined for the Scottish population in a retrospective cohort design for winter 2003/2004. Details of all IPD cases were obtained from the central reference laboratory and population vaccine uptake information was estimated from a GP sentinel practice network. Based on the preceding four winter seasons, standardised incidence ratios (SIR) for invasive pneumococcal disease were determined by age-band and sex during winter 2003/2004. Vaccination effectiveness (VE) was estimated using both screening and indirect cohort methods. Numbers needed to vaccinate were derived from VE results using equivalent annual incidence estimates for winter 2003/2004. RESULTS: Overall vaccination effectiveness using the screening method (adjusted for age and sex) in those aged 65 and over was 61.7% (95%CI: 45.1, 73.2) which corresponded to a number needed to vaccinate of 5206 (95%CI: 4388, 7122) per IPD case prevented. Estimated effectiveness for the same age group using the indirect cohort method was not significant at 51% (95%CI: -278, 94). Reductions in the winter season incidence rate of IPD were highly significant for all those aged 75+: males SIR = 58.8 (95%CI: 41.6, 80.8); females SIR = 70.0 (95%CI: 55.1, 87.8). In the 65-74 years age-group, the reduction for females was significant: SIR = 60.3 (95%CI: 39.3, 88.4), but not for males: SIR = 74.8 (95%CI: 50.8, 106.3). There was no significant protective effect on mortality. CONCLUSION: The introduction of 23vPPV for those aged 65 and over in Scotland during winter 2003/2004, was accompanied with a reduction of around one third in the incidence of IPD in this age group. Vaccination effectiveness estimates were comparable with those from other developed countries.

Assessing the impact of a temporary class drug order on ethylphenidate-related infections among people who inject drugs in Lothian, Scotland: an interrupted time-series analysis.

BACKGROUND AND AIMS: In April 2015, the UK government enacted a temporary class drug order (TCDO) on ethylphenidate in response to reported harms associated with its use, in particular an outbreak of infections among people who inject drugs (PWID) in Lothian, Scotland. This study assesses the effect that the TCDO had on reducing the most common infections identified during the outbreak: Streptococcus pyogenes and Staphylococcus aureus. DESIGN: The outbreak was split into a pre-intervention period (35 weeks) and a post-intervention period (26 weeks) based around the date of the TCDO. Segmented negative binomial regression models were used to compare trends in weekly counts of infections between the pre- and post-intervention periods. SETTING AND PARTICIPANTS: PWID in the Lothian region of Scotland. MEASUREMENTS: Cases of S. pyogenes and S. aureus infections reported within the National Health Service, Lothian. FINDINGS: There were 251 S. pyogenes and/or S. aureus infections recorded among 211 PWID between February 2014 and December 2015: 171 infections in the pre-intervention period and 51 in the post-intervention period. Significant trend changes in weekly S. pyogenes and/or S. aureus infections following the TCDO were found [relative risk (RR) = 0.88, 95% confidence interval (CI) = 0.82-0.94]. PWID who self-reported using novel psychoactive substances (NPS) were at higher risk of acquiring these infections (RR = 1.81, 95% CI = 1.12-2.93), particularly when comparing the risk of infection with NPS use for a specific strain, S. pyogenes emm76.0, against the risk of infection with NPS use for S. pyogenes (emm types other than emm76.0) (RR = 3.49, 95% CI = 1.32-9.21). CONCLUSIONS: The UK government's 2015 temporary class drug order on ethylphenidate was effective in reducing infections among people who inject drugs during an outbreak situation in Lothian, Scotland.

Hepatitis C reinfection following treatment induced viral clearance among people who have injected drugs.

BACKGROUND: Although people who inject drugs (PWID) are an important group to receive Hepatitis C Virus (HCV) antiviral therapy, initiation onto treatment remains low. Concerns over reinfection may make clinicians reluctant to treat this group. We examined the risk of HCV reinfection among a cohort of PWID (encompassing all those reporting a history of injecting drug use) from Scotland who achieved a sustained virological response (SVR). METHODS: Clinical and laboratory data were used to monitor RNA testing among PWID who attained SVR following therapy between 2000 and 2009. Data were linked to morbidity and mortality records. Follow-up began one year after completion of therapy, ending on 31st December, 2012. Frequency of RNA testing during follow-up was calculated and the incidence of HCV reinfection estimated. Cox proportional hazards regression was used to examine factors associated with HCV reinfection. RESULTS: Among 448 PWID with a SVR, 277 (61.8%) were tested during follow-up, median 4.5 years; 191 (69%) received one RNA test and 86 (31%) received at least two RNA tests. There were seven reinfections over 410 person years generating a reinfection rate of 1.7/100py (95% CI 0.7-3.5). For PWID who have been hospitalised for an opiate or injection related cause post SVR (11%), the risk of HCV reinfection was greater [AHR=12.9, 95% CI 2.2-76.0, p=0.002] and the reinfection rate was 5.7/100py (95% CI 1.8-13.3). CONCLUSION: PWID who have been tested, following SVR, for HCV in Scotland appear to be at a low risk of reinfection. Follow-up and monitoring of this population are warranted as treatment is offered more widely.

Mortality and cause of death in a cohort of people who had ever injected drugs in Glasgow: 1982-2012.

BACKGROUND: To describe all-cause and cause-specific mortality in a cohort of people who had ever injected drugs (PWID) with a low prevalence of HIV over 20-30 years. METHODS: Using a retrospective study design, identifying data from a cohort of PWID recruited between 1982 and 1993 through in-patient drug treatment services were linked to National Records for Scotland deaths data using probabilistic record linkage. We report all-cause and cause-specific mortality rates; standardized mortality ratios (SMR) across time, gender and age were estimated. RESULTS: Among 456 PWID, 139 (30.5%) died over 9024 person-years (PY) of follow-up. Mortality within the cohort was almost nine times higher than the general population, and remained elevated across all age groups. The greatest excess mortality rate was in the youngest age group, who were 15-24 years of age (SMR 31.6, 95% CI 21.2-47.1). Drug-related deaths declined over time and mortality was significantly higher among HIV positive participants. Although SMRs declined with follow-up, the SMR of the oldest age group (45-60) was 4.5 (95% CI 3.0-6.9). There were no significant differences in all-cause mortality rates between participants who were 25 years and older at cohort entry compared to younger participants. CONCLUSION: Mortality rates remained higher than the general population across all age groups. Screening services that identify a history of injecting drug use may be an opportunity to address risk factors faced by an ageing population of PWID and potentially have implications for future health care planning.

Expansion of HCV treatment access to people who have injected drugs through effective translation of research into public health policy: Scotland's experience.

Seven years have elapsed since the Scottish Government launched its Hepatitis C Action Plan - a Plan to improve services to prevent transmission of infection, particularly among people who inject drugs (PWID), identify those infected and ensure those infected receive optimal treatment. The Plan was underpinned by industrial scale funding (around £100 million, in addition to the general NHS funding, will have been invested by 2015), and a web of accountable national and local multi-disciplinary multi-agency networks responsible for the planning, development and delivery of services. Initiatives ranged from the introduction of testing in specialist drug services through finger-prick blood sampling by non-clinical staff, to the setting of government targets to ensure rapid scale-up of antiviral therapy. The Plan was informed by comprehensive national monitoring systems, indicating the extent of the problem not just in terms of numbers infected, diagnosed and treated but also the more penetrative data on the number advancing to end-stage liver disease and death, and also through compelling modelling work demonstrating the potential beneficial impact of scaling-up therapy and the mounting cost of not acting. Achievements include around 50% increase in the proportion of the infected population diagnosed (38% to 55%); a sustained near two-and-a-half fold increase in the annual number of people initiated onto therapy (470 to 1050) with more pronounced increases among PWID (300 to 840) and prisoners (20 to 140); and reversing of an upward trend in the overall number of people living with chronic infection. The Action Plan has demonstrated that a Government-backed, coordinated and invested approach can transform services and rapidly improve the lives of thousands. Cited as "an impressive example of a national strategy" by the Global Commission on Drug Policy, the Scottish Plan has also provided fundamental insights of international relevance into the management of HCV among PWID.

Evidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: Implications for reinfection.

BACKGROUND: People who inject drugs (PWID) are at the greatest risk of hepatitis C virus (HCV) infection, yet are often denied immediate treatment due to fears of on-going risk behaviour. Our principal objective was to examine evidence of continued injecting drug use among PWID following successful treatment for HCV and attainment of a sustained viral response (SVR). METHODS: PWID who attained SVR between 1992 and June 2012 were selected from the National Scottish Hepatitis C Clinical Database. Hospitalisation and mortality records were sourced for these patients using record linkage techniques. Our primary outcome variable was any hospitalisation or death, which was indicative of injecting drugs post-SVR. RESULTS: The cohort comprised 1170 PWID (mean age at SVR 39.6y; 76% male). The Kaplan Meier estimate of incurring the primary outcome after three years of SVR was 10.59% (95% CI, 8.75-12.79) After adjusting for confounding, the risk of an injection related hospital episode or death post-SVR was significantly increased with advancing year of SVR: AHR:1.07 per year (95% CI, 1.01-1.14), having a pre-SVR acute alcohol intoxication-related hospital episode: AHR:1.83 (95% CI, 1.29-2.60), and having a pre-SVR opiate or injection-related hospital episode: AHR:2.59 (95% CI, 1.84-3.64). CONCLUSION: Despite attaining the optimal treatment outcome, these data indicate that an increasing significant minority of PWID continue to inject post-SVR at an intensity which leads to either hospitalisation or death and increased risk of reinfection.