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Abstract Background Despite increased awareness of the significant health and healthcare inequalities experienced by minoritised groups, limited research considers the interaction of multiple domains of social disadvantage. This review therefore sought to explore how LGBTQ + adults’ experiences of homelessness, substance use, and criminal justice involvement impact upon their access to and use of health and social care services in the UK and Ireland. Methods A qualitative scoping review was conducted in accordance with the PRISMA-ScR framework. Electronic database and web searches identified 26 eligible peer-reviewed and grey literature documents published between 2010–2024. The data were charted, coded, and knowledge gaps identified. Results Data were coded thematically, clustered around the concept of normativity. Descriptive qualitative techniques were applied to explore how this was enacted and experienced. Synthesis across the literature identified experiences of discrimination and anticipated stigma that acted as barriers to accessing and engaging with services. Conclusions Structural normativity and the privilege afforded to hegemonic population groups impacted upon this population’s access to and use of services. The review adds depth and context to questions around the lack of visibility or engagement in services by LGBTQ + people with experience of disadvantage, and contributes to the wider literature on improving service access for marginalised, underserved, or disadvantaged communities.

Abstract Background Alcohol-related mortality and morbidity increased during the COVID-19 pandemic in England, with people from lower-socioeconomic groups disproportionately affected. The North East and North Cumbria (NENC) region has high levels of deprivation and the highest rates of alcohol-related harm in England. Consequently, there is an urgent need for the implementation of evidence-based preventative approaches such as identifying people at risk of alcohol harm and providing them with appropriate support. Non-alcohol specialist secondary care clinicians could play a key role in delivering these interventions, but current implementation remains limited. In this study we aimed to explore current practices and challenges around identifying, supporting, and signposting patients with Alcohol Use Disorder (AUD) in secondary care hospitals in the NENC through the accounts of staff in the post COVID-19 context. Methods Semi-structured qualitative interviews were conducted with 30 non-alcohol specialist staff (10 doctors, 20 nurses) in eight secondary care hospitals across the NENC between June and October 2021. Data were analysed inductively and deductively to identify key codes and themes, with Normalisation Process Theory (NPT) then used to structure the findings. Results Findings were grouped using the NPT domains ‘implementation contexts’ and ‘implementation mechanisms’. The following implementation contexts were identified as key factors limiting the implementation of alcohol prevention work: poverty which has been exacerbated by COVID-19 and the prioritisation of acute presentations (negotiating capacity); structural stigma (strategic intentions); and relational stigma (reframing organisational logics). Implementation mechanisms identified as barriers were: workforce knowledge and skills (cognitive participation); the perception that other departments and roles were better placed to deliver this preventative work than their own (collective action); and the perceived futility and negative feedback cycle (reflexive monitoring). Conclusions COVID-19, has generated additional challenges to identifying, supporting, and signposting patients with AUD in secondary care hospitals in the NENC. Our interpretation suggests that implementation contexts, in particular structural stigma and growing economic disparity, are the greatest barriers to implementation of evidence-based care in this area. Thus, while some implementation mechanisms can be addressed at a local policy and practice level via improved training and support, system-wide action is needed to enable sustained delivery of preventative alcohol work in these settings.

Abstract Background Innovation for reforming health and social care is high on the policy agenda in the United Kingdom in response to the growing needs of an ageing population. However, information about new innovations of care being implemented is sparse. Methods We mapped innovations for people in later life in two regions, North East England and South East Scotland. Data collection included discussions with stakeholders (n = 51), semi-structured interviews (n = 14) and website searches that focused on technology, evaluation and health inequalities. We analysed qualitative data using framework and thematic analyses. Quantitative data were analysed descriptively. Results One hundred eleven innovations were identified across the two regions. Interviewees reported a wide range of technologies that had been rapidly introduced during the COVID-19 pandemic and many remained in use. Digital exclusion of certain groups of older people was an ongoing concern. Innovations fell into two groups; system-level ones that aimed to alleviate systems pressures such as preventing hospital (re)admissions, and patient-level ones which sought to enhance health and wellbeing directly. Interviewees were aware of the importance of health inequalities but lacked data to monitor the impact of innovations on these, and evaluation was challenging due to lack of time, training, and support. Quantitative findings revealed that two thirds of innovations (n = 74, 67%) primarily focused on the system level, whilst a third (n = 37, 33%) primarily focused on the patient-level. Overall, over half (n = 65, 59%) of innovations involved technologies although relatively few (n = 12, 11%) utilised advanced technologies. Very few (n = 16, 14%) focused on reducing health inequalities, and only a minority of innovations (n = 43, 39%) had undergone evaluation (most of which were conducted by the service providers themselves). Conclusions We found a wide range of innovative care services being developed for people in later life, yet alignment with key policy priorities, such as addressing health inequalities, was limited. There was a strong focus on technology, with little consideration for the potential to widen the health inequality gap. The absence of robust evaluation was also a concern as most innovations were implemented without support to monitor effectiveness and/or without plans for sustainability and spread.

Abstract Background Opioid use is a major public health concern across the globe. Opioid use and subsequent access to care is often shaped by co-occurring issues faced by people using opioids, such as deprivation, mental ill-health, and other forms of substance use. We investigated the role of social deprivation and comorbid mental health diagnoses in predicting re-engagement with substance use services or contact with crisis and inpatient services for individuals with opioid use disorder in secondary mental health care in inner-city London. Methods We conducted a prospective cohort study which followed individuals diagnosed with a first episode of opioid use disorder who accessed substance use services between September 2015 and May 2020 for up to 12 months, using anonymised electronic health records. We employed negative binominal regression and Cox proportional survival analyses to assess associations between exposures and outcomes. Results Comorbid mental health diagnoses were associated with higher contact rates with crisis/inpatient services among people with opioid use disorder: incidence rate ratios (IRR) and 95% confidence intervals (CI) were 3.91 (1.74–9.14) for non-opioid substance use comorbidity, 8.92 (1.81–64.4) for a single comorbid mental health diagnosis, and 15.9 (5.89–47.5) for multiple comorbid mental health diagnoses. Social deprivation was not associated with contact rates with crisis/inpatient services within this sample. Similar patterns were found with time to first crisis/inpatient contact. Social deprivation and comorbid mental health diagnoses were not associated with re-engagement with substance use services. Conclusion Comorbid substance and mental health difficulties amongst people with an opioid use disorder led to earlier and more frequent contact with crisis/inpatient mental health services during the first 12 months of follow up. Given the common co-occurrence of mental health and substance use disorders among those who use opioids, a better understanding of their wider needs (such as social, financial and other non-medical concerns) will ensure they are supported in their treatment journeys.

Objectives To examine the effectiveness of shared medical appointments (SMAs) compared with one-to-one appointments in primary care for improving health outcomes and reducing demand on healthcare services by people with one or more long-term conditions (LTCs).Design A systematic review of the published literature.Data sources Six databases, including MEDLINE and Web of Science, were searched 2013–2023. Relevant pre-2013 trials identified by forward and backward citation searches of the included trials were included.Eligibility criteria Randomised controlled trials of SMAs delivered in a primary care setting involving adults over 18 years with one or more LTCs. Studies were excluded if the SMA did not include one-to-one patient-clinician time. All countries were eligible for inclusion.Data extraction and synthesis Data were extracted and outcomes narratively synthesised, meta-analysis was undertaken where possible.Results Twenty-nine unique trials were included. SMA models varied in terms of components, mode of delivery and target population. Most trials recruited patients with a single LTC, most commonly diabetes (n=16). There was substantial heterogeneity in outcome measures. Meta-analysis showed that participants in SMA groups had lower diastolic blood pressure than those in usual care (d=−0.086, 95% CI=−0.16 to –0.02, n=10) (p=0.014). No statistically significant differences were found across other outcomes. Compared with usual care, SMAs had no significant effect on healthcare service use. For example, no difference between SMAs and usual care was found for admissions to emergency departments at follow-up (d=−0.094, 95% CI=−0.27 to 0.08, n=6, p=0.289).Conclusions There was a little difference in the effectiveness of SMAs compared with usual care in terms of health outcomes or healthcare service use in the short-term (range 12 weeks to 24 months). To strengthen the evidence base, future studies should include a wider array of LTCs, standardised outcome measures and more details on SMA components to help inform economic evaluation.PROSPERO registration number CRD42020173084.

Objectives Lung cancer continues to be the most common cause of cancer-related death and the leading cause of morbidity and burden of disease across Australia. There is an ongoing need to identify and reduce unwarranted clinical variation that may contribute to these poor outcomes for patients with lung cancer. An Australian national strategy acknowledges clinical quality outcome data as a critical component of a continuously improving healthcare system but there is a need to ensure clinical quality indicators adequately measure evidence-based contemporary care, including novel and emerging treatments. This study aimed to develop a suite of lung cancer-specific, evidence-based, clinically acceptable quality indicators to measure quality of care and outcomes, and an associated comparative feedback dashboard to provide performance data to clinicians and hospital administrators.Design A multistage modified Delphi process was undertaken with a Clinical Advisory Group of multidisciplinary lung cancer specialists, with patient representation, to update and prioritise potential indicators of lung cancer care derived from a targeted review of published literature and reports from national and international lung cancer quality registries. Quality indicators were piloted and evaluated with multidisciplinary teams in a retrospective observational cohort study using clinical audit data from the Embedding Research (and Evidence) in Cancer Healthcare Program, a prospective clinical cohort of over 2000 patients with lung cancer diagnosed from May 2016 to October 2021.Setting and participants Six tertiary specialist cancer centres in metropolitan and regional New South Wales, Australia.Results From an initial 37 potential quality indicators, a final set of 10 indicators spanning diagnostic, treatment, quality of life and survival domains was agreed.Conclusions These indicators build on and update previously available measures of lung cancer care and outcomes in use by national and international lung cancer clinical quality registries which, to our knowledge, have not been recently updated to reflect the changing lung cancer treatment paradigm.

Abstract Background Shared medical appointments (SMAs) or group consultations have been promoted in primary care to improve workload pressures, resource-use efficiency and patient self-management of long-term conditions (LTCs). However, few studies have explored stakeholders’ perspectives of this novel care delivery model in the English NHS context, particularly patients’ views and experiences of SMAs. Method Semi-structured interviews were used to explore the perspectives of stakeholders (21 patients, 17 primary care staff, 2 commissioners and 2 SMA training providers) with and without SMA experience from a range of geographical and socio-economic backgrounds in the North East and North Cumbrian region of England. Thematic analysis was conducted to examine perceptions around impact on patient care and outcomes and barriers and facilitators to implementation. Results Three main themes were identified: ‘Value of sharing’, ‘Appropriateness of group setting’, ‘Implementation processes’. Patients experiences and perceptions of SMAs were largely positive yet several reported reservations about sharing personal information, particularly in close-knit communities where the risk of breaching confidentiality was perceived to be greater. SMAs were considered by patients and staff to be inappropriate for certain personal conditions or for some patient groups. Staff reported difficulties engaging sufficient numbers of patients to make them viable and having the resources to plan and set them up in practice. Whilst patients and staff anticipated that SMAs could deliver high quality care more efficiently than 1:1 appointments, none of the practices had evaluated the impact SMAs had on patient health outcomes or staff time. Conclusion Stakeholder experiences of SMA use in English primary care are largely similar to those reported in other countries. However, several important cultural barriers were identified in this setting. Further work is needed to better understand how patient and staff perceptions, experiences and engagement with SMAs change with regular use over time. Concerns regarding staff capacity, additional resource requirements and numbers of eligible patients per practice suggest SMAs may only be feasible in some smaller practices if facilitated by primary care networks. Further mixed-method evaluations of SMAs are needed to inform the evidence base regarding the effectiveness, efficiency and feasibility of SMAs long-term and subsequently their wider roll-out in English primary care.

While nest usurpation and subsequent incubation of eggs and even brooding of chicks from other species has been reported for Common Terns (Sterna hirundo), such behavior is considered rare. We report an observation of a Common Tern pair usurping the Least Tern (Sternula antillarum) nest and brooding the Least Tern chicks. While the Least Tern pair attempted to provide care for the chicks, the Common Terns displayed aggressive behavior and defended the nest. Though both species attempted to feed the chicks, no feeding events were observed due to harassment from the other species. Neither pair was observed nesting prior to or following this event, and all chicks are believed to have been lost to predation. We discuss the possible scenarios leading to the observed usurpation event, the possibility that usurpations are more common than previously believed, and the need for different monitoring methods to elucidate the causes of usurpations.

Objectives: To examine the association between educational level and attitudes towards alcohol conversations in healthcare using population-based surveys of adults in England, the Netherlands, Norway, and Sweden; and to compare attitudes towards alcohol conversations in healthcare between these four countries.Methods: Cross-sectional surveys were conducted amongst adults in the general population in England (n = 3,499), the Netherlands (n = 2,173), Norway (n = 1,208), and Sweden (n = 3,000). Logistic regression analysis was used to examine associations between attitudes towards alcohol conversations in healthcare and educational level, key demographic variables, alcohol consumption, and country of residence.Results: In all four countries, low educational level (p < 0.001) and male gender (p < 0.001) were associated with holding negative attitudes towards discussing alcohol in healthcare. Risky drinkers had more negative attitudes than low risky drinkers towards discussing alcohol in healthcare (p < 0.001) in all countries except England (p = 0.48), and also reported low levels of perceived honesty and confidence in healthcare (p < 0.001).Conclusion: These findings highlight the importance of considering patients’ socio-economic status when developing and implementing alcohol prevention interventions in healthcare.

Researchers and practitioners recognise the importance of context when implementing healthcare interventions, but the influence of wider environment is rarely mapped. This paper identifies the country and policy-related factors potentially explaining the country differences in outcomes of an intervention focused on improving detection and management of heavy alcohol use in primary care in Colombia, Mexico and Peru. Qualitative data obtained through interviews, logbooks and document analysis are used to explain quantitative data on number of alcohol screenings and screening providers in each of the countries. Existing alcohol screening standards in Mexico, and policy prioritisation of primary care and consideration of alcohol as a public health issue in Colombia and Mexico positively contributed to the outcome, while the COVID-19 pandemic had a negative impact. In Peru, the context was unsupportive due to a combination of: political instability amongst regional health authorities; lack of focus on strengthening primary care due to the expansion of community mental health centres; alcohol considered as an addiction rather than a public health issue; and the impact of COVID-19 on healthcare. We found that wider environment-related factors interacted with the intervention implemented and can help explain country differences in outcomes.

Background Effective interventions exist for heavy drinking and depression but to date there has been limited translation into routine practice in global health systems. This evidence-to-practice gap is particularly evident in low- and middle-income countries. The international SCALA project (Scale-up of Prevention and Management of Alcohol Use Disorders and Comorbid Depression in Latin America) sought to test the impact of multilevel implementation strategies on rates of primary health care-based measurement of alcohol consumption and identification of depression in Colombia, Mexico, and Peru. Objective To describe the process of development and cultural adaptation of the clinical intervention and training package. Methods We drew on Barrero and Castro’s four-stage cultural adaption model: 1) information gathering, 2) preliminary adaption, 3) preliminary adaption tests, and 4) adaption refinement. The Tailored Implementation in Chronic Diseases checklist helped us identify potential factors that could affect implementation, with local stakeholder groups established to support the tailoring process, as per the Institute for Healthcare Improvement’s Going to Scale Framework. Results In Stage 1, international best practice guidelines for preventing heavy drinking and depression, and intelligence on the local implementation context, were synthesised to provide an outline clinical intervention and training package. In Stage 2, feedback was gathered from local stakeholders and materials refined accordingly. These materials were piloted with local trainers in Stage 3, leading to further refinements including developing additional tools to support delivery in busy primary care settings. Stage 4 comprised further adaptions in response to real-world implementation, a period that coincided with the onset of the COVID-19 pandemic, including translating the intervention and training package for online delivery, and higher priority for depression screening in the clinical pathway. Conclusion Our experience highlights the importance of meaningful engagement with local communities, alongside the need for continuous tailoring and adaptation, and collaborative decision-making.

Abstract Background SARS-CoV-2 reached Europe in early 2020 and disrupted the private and public life of its citizens, with potential implications for substance use. The objective of this study was to describe possible changes in substance use in the first months of the SARS-CoV-2 pandemic in Europe. Methods Data were obtained from a cross-sectional online survey of 36,538 adult substance users from 21 European countries conducted between April 24 and July 22 of 2020. Self-perceived changes in substance use were measured by asking respondents whether their use had decreased (slightly or substantially), increased (slightly or substantially), or not changed during the past month. The survey covered alcohol (frequency, quantity, and heavy episodic drinking occasions), tobacco, cannabis, and other illicit drug use. Sample weighted data were descriptively analysed and compared across substances. Results Across all countries, use of all substances remained unchanged for around half of the respondents, while the remainder reported either a decrease or increase in their substance use. For alcohol use, overall, a larger proportion of respondents indicated a decrease than those reporting an increase. In contrast, more respondents reported increases in their tobacco and cannabis use during the previous month compared to those reporting decreased use. No distinct direction of change was reported for other substance use. Conclusions Our findings suggest changes in use of alcohol, tobacco and cannabis during the initial months of the pandemic in several European countries. This study offers initial insights into changes in substance use. Other data sources, such as sales statistics, should be used to corroborate these preliminary findings.

Background Initial results from the SCALA study demonstrated that training primary health care providers is an effective implementation strategy to increase alcohol screening in Colombia, Mexico and Peru, but did not show evidence of superior performance for the standard compared to the shorter training arm. This paper elaborates on those outcomes by examining the relationship of training-related process evaluation indicators with the alcohol screening practice. Methods A mix of convergent and exploratory mixed-methods design was employed. Data sources included training documentation, post-training questionnaires, observation forms, self-report forms and interviews. Available quantitative data were compared on outcome measure – providers’ alcohol screening. Results Training reach was high: three hundred fifty-two providers (72.3% of all eligible) participated in one or more training or booster sessions. Country differences in session length reflected adaptation to previous topic knowledge and experience of the providers. Overall, 49% of attendees conducted alcohol screening in practice. A higher dose received was positively associated with screening, but there was no difference between standard and short training arms. Although the training sessions were well received by participants, satisfaction with training and perceived utility for practice were not associated with screening. Profession, but not age or gender, was associated with screening: in Colombia and Mexico, doctors and psychologists were more likely to screen (although the latter represented only a small proportion of the sample) and in Peru, only psychologists. Conclusions The SCALA training programme was well received by the participants and led to half of the participating providers conducting alcohol screening in their primary health care practice. The dose received and the professional role were the key factors associated with conducting the alcohol screening in practice. Plain Language Summary: Primary health care providers can play an important role in detecting heavy drinkers among their consulting patients, and training can be an effective implementation strategy to increase alcohol screening and detection. Existing training literature predominantly focuses on evaluating trainings in high-income countries, or evaluating their effectiveness rather than implementation. As part of SCALA (Scale-up of Prevention and Management of Alcohol Use Disorders in Latin America) study, we evaluated training as implementation strategy to increase alcohol screening in primary health care in a middle-income context. Overall, 72.3% of eligible providers attended the training and 49% of training attendees conducted alcohol screening in practice after attending the training. Our process evaluation suggests that simple intervention with sufficient time to practice, adapted to limited provider availability, is optimal to balance training feasibility and effectiveness; that booster sessions are especially important in context with lower organizational or structural support; and that ongoing training refinement during the implementation period is necessary.

Objective To assess the immediate impact of the introduction of minimum unit pricing (MUP) in Scotland on alcohol consumption and whether the impact differed by sex, level of alcohol consumption, age, social grade and level of residential deprivation of respondents.Design Primary controlled interrupted time series analysis and secondary before-and-after analysis of the impact of introducing MUP in Scotland using alcohol consumption data for England as control.Setting Data from Kantar Worldpanel’s Alcovision survey, a continuous retrospective online timeline follow-back diary survey of the previous week’s alcohol consumption.Participants 53 347 women and 53 143 men.Interventions Introduction of a minimum price of 50 pence per UK unit (6.25 pence/g) for the sale of alcohol in Scotland on 1 May 2018.Main outcome measures Number of grams of alcohol consumed per week, in total, in off-trade (eg, at home) and in on-trade (eg, in pubs, restaurants).Results Primary interrupted time series analyses found that the introduction of MUP was associated with a drop in reported weekly total alcohol consumption of 5.94 g (95% CI 1.29 to 10.60), a drop in off-trade consumption of 3.27 g (95% CI −0.01 to 6.56) and a drop in on-trade consumption of 2.67 g (95% CI −1.48 to 6.82). Associated reductions were larger for women than for men and were greater among heavier drinkers than for lighter drinkers, except for the 5% of heaviest drinking men for whom an associated increase in consumption was found. Secondary before-and-after analyses found that reductions in consumption were greater among older respondents and those living in less deprived areas. The introduction of MUP was not associated with a reduction in consumption among younger men and men living in more deprived areas.Conclusions Greater policy attention needs to be addressed to the heaviest drinking men, to younger men and to men who live in more deprived areas.

Primary care databases extract and combine routine data from the electronic patient records of various participating practices on a regular basis. These databases can be used for innovative and relevant addiction research, but such use requires a thorough understanding of how data were originally collected and how they need to be processed and statistically analysed to produce sound scientific evidence. The aims of this paper are therefore to (1) make a case for why primary care databases should be considered more frequently for addiction research; (2) provide an overview of how primary care databases are constructed; (3) highlight important methodological and statistical strengths and weaknesses of using primary care databases for research; and (4) give practical advice about how a researcher can get access to databases. Three major primary care databases from the UK serve as examples: Clinical Practice Research Datalink (CPRD), The Health Improvement Network (THIN), and QResearch.

Abstract Background Despite evidence supporting the effectiveness of alcohol screening and brief advice to reduce heavy drinking, implementation in primary healthcare remains limited. The challenges that clinicians experience when delivering such interventions are well-known, but we have little understanding of the patient perspective. We used Normalization Process Theory (NPT) informed interviews to explore patients’ views on alcohol screening and brief advice in routine primary healthcare. Methods Semi-structured qualitative interviews with 22 primary care patients who had been screened for heavy drinking and/or received brief alcohol advice were analysed thematically, informed by Normalisation Process Theory constructs (coherence, cognitive participation, collective action, reflexive monitoring). Results We found mixed understanding of the adverse health consequences of heavy drinking, particularly longer-term risks. There was some awareness of current alcohol guidelines but these were viewed flexibly, depending on the individual drinker and drinking context. Most described alcohol screening as routine, with clinicians viewed as trustworthy and objective. Patients enacted a range of self-regulatory techniques to limit their drinking but perceived such strategies as learned through experience rather than based on clinical advice. However, most saw alcohol advice as a valuable component of preventative healthcare, especially those experiencing co-occurring health conditions. Conclusions Despite strong acceptance of the screening role played by primary care clinicians, patients have less confidence in the effectiveness of alcohol advice. Primary care-based alcohol brief advice needs to reflect how individuals actually drink, and harness strategies that patients already commonly employ, such as self-regulation, to boost its relevance.

Abstract Background This study evaluated and compared the extent, duration, contents, experiences and effects of alcohol conversations in healthcare in the Netherlands and Sweden in 2017. Methods Survey data in the Netherlands and Sweden were collected through an online web panel. Subjects were 2996 participants (response rate: 50.8%) in Sweden and 2173 (response rate: 82.2%) in the Netherlands. Data was collected on socio-demographics, alcohol consumption, healthcare visits in the past 12 months, number of alcohol conversations, and characteristics of alcohol conversations (duration, contents, experience, effects). Results Results showed that Swedish respondents were more likely to have had alcohol conversations (OR = 1.99; 95%CI = 1.64–2.41; p =

High quality human tissue is essential for molecular research, but pre-analytical conditions encountered during tissue collection could degrade tissue RNA. We evaluated how prolonged exposure of non-diseased breast tissue to ambient room temperature (22±1°C) impacted RNA quality. Breast tissue received between 70 to 190 minutes after excision was immediately flash frozen (FF) or embedded in Optimal Cutting Temperature (OCT) compound upon receipt (T0). Additional breast tissue pieces were further exposed to increments of 60 (T1 = T0+60 mins), 120 (T2 = T0+120 mins) and 180 (T3 = T0+180 mins) minutes of ambient room temperature before processing into FF and OCT. Total exposure, T3 (T0+180 mins) ranged from 250 minutes to 370 minutes. All samples (FF and OCT) were stored at -80°C before RNA isolation. The RNA quality assessment based on RNA Integrity Number (RIN) showed RINs for both FF and OCT samples were within the generally acceptable range (mean 7.88±0.90 to 8.52±0.66). No significant difference was observed when RIN at T0 was compared to RIN at T1, T2 and T3 (FF samples, p = 0.43, 0.56, 0.44; OCT samples, p = 0.25, 0.82, 1.0), or when RIN was compared between T1, T2 and T3. RNA quality assessed by quantitative real-time PCR (qRT-PCR) analysis of beta-actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cyclophilin A (CYPA), and porphobilinogen deaminase (PBGD) transcripts showed threshold values (Ct) that indicate abundant and intact target nucleic acid in all samples (mean ranging from 14.1 to 25.3). The study shows that higher RIN values were obtained for non-diseased breast tissue up to 190 minutes after resection and prior to stabilization. Further experimental exposure up to 180 minutes had no significant effect on RIN values. This study strengthens the rationale for assessing RIN and specific gene transcript levels as an objective method for determining how suitable RNA will be for a specific research purpose ("fit-for purpose").

British supermarket-panel data suggest no increases in overall sales and purchases of alcohol following COVID-19 lockdowns, yet survey and mortality data suggest otherwise. This paper attempts to unravel the paradox. Based on purchase data of 79,417 British households from Kantar Worldpanel, we undertake controlled interrupted time series analysis of the impact of COVID-19 confinement introduced on 23rd March 2020, and variably applied during 2020, compared to purchases during 2015 to 2019 as controls. We also undertook Poisson regression analyses to estimate if changes in purchases differed by household socio-demographic and economic factors. Excess off-trade household alcohol purchases (expressed as grams of ethanol) following the introduction of confinement, were 29.2% higher (95% CI = 25.8% to 32.5%) for the post-confinement months of 2020, being larger until mid-July 2020 (37.5%, 95%CI = 33.9 to 41.26%) when pubs re-opened with restrictions, and smaller (24.6%, 95%CI = 21.6 to 27.7) thereafter. During the time of complete pub closures, and fully adjusting for no on-trade purchases, household purchases of alcohol did not change when compared with the same time period during 2015–2019 (coefficient = -0.9%, 95%CI = -5.6 to 3.8). Excess purchases from 23rd March to 31st December 2020 varied by region of Great Britain, being higher in the north of England, and lower in Scotland and Wales. Excess purchases were greater in the most deprived households, compared with the least deprived households. Excess purchases increased substantially as the amount of alcohol normally purchased by a household increased, with the top one fifth of households that normally bought the most alcohol increasing their purchases more than 17 times than the bottom one fifth of households that bought the least alcohol. That the heaviest buyers of alcohol increased their purchases the most, with some independent impact of socio-economic disadvantage, might explain why reported alcohol problems and recent alcohol-related death rates might have increased. A conclusion of this is that alcohol policy to reduce high consumption of alcohol, and the availability of help and treatment to reduce alcohol consumption become more important during extraordinary times, such as COVID lockdowns.

Substance use and mental ill health constitute a major public health burden, and a key global policy priority is to reduce illicit and other harmful substance use. Amphetamine-type stimulants (ATS) are the second most used class of illicit drugs and a range of mental health issues have been documented amongst users. This paper explores the relationship between mental health and ATS use, through a thematic analysis of qualitative interviews with n = 18 current and former ATS users in England. The findings are presented by trajectory point of; (1) Initiation of ATS use; (2) continued and increased ATS use and (3) decreased and remitted ATS use. This work helps to develop understanding around the complex and bi-directional relationship between ATS use and mental health. Many ATS users lead chaotic lives and engage in multiple risk behaviours, however there is a need to better understand and conceptualise the dynamic interaction between different individual, social, environment and cultural factors that determine individuals’ mental health and substance use. There is no ‘one size fits all’ approach to prevention and treatment, and these findings highlight the need for more joined-up, tailored and holistic approaches to intervention development.

Objectives: To identify the proportion of the population that had experienced that alcohol was addressed in health care the previous year, to explore experiences and perceived effects of addressing alcohol, and to investigate the proportion of risky drinkers in the population.Methods: Cross-sectional national web-based survey with 1,208 participants. Socio-demographic data, alcohol consumption (AUDIT-C), and experiences with alcohol conversations were investigated.Results: Approximately four in five respondents had visited health care the past 12 months, and one in six reported having experienced addressing alcohol. Women and older respondents were less likely to report having experienced alcohol conversations compared to other groups. Risky drinkers were not more likely to have experienced an alcohol conversation, but reported longer duration of alcohol conversations and more frequently perceived addressing alcohol as awkward or judgmental. Almost a third of respondents were classified as risky drinkers.Conclusion: The proportion experiencing addressing alcohol in routine health care is low, also among risky drinkers, and risky drinkers more frequently experienced the conversations as judgmental. More sensitive and relevant ways of addressing alcohol in health care is needed.

Abstract Background Identifying and addressing heavy drinking represents a major public health priority worldwide. Whilst the majority of alcohol screening and brief intervention (ASBI) research has been conducted in western, high-income countries, evidence is growing that ASBI can also impact positively on heavy drinkers in low- and middle-income country populations. This mixed methods study aims to assess the feasibility of conducting a fully randomised controlled trial of the effectiveness of ASBI in primary care in Kazakhstan and explore the feasibility and acceptability of implementing ASBI in this setting from patients’ and physicians’ perspectives. Methods Six primary health care units in the region of Pavlodar will be cluster randomised to either an intervention (WHO manualised 5 min alcohol brief intervention plus alcohol leaflet) or control group (simple feedback plus alcohol leaflet). Primary feasibility measures will be rates of participation at baseline and retention of eligible patients at the 3-month follow-up point. Patient/physician questionnaires and physician focus groups will assess additional dimensions of feasibility, as well as acceptability, according to the RE-AIM framework: Reach (rates of eligible patients screened/received advice); Effectiveness (change in AUDIT-C score); Adoption (rate/representativeness of participating physicians); Implementation (quality of ASBI/barriers and facilitators to delivery); and Maintenance (potential sustainability of intervention). Discussion This is the first trial of the feasibility and acceptability of ASBI in Kazakhstan. As the planning and assessment of implementation determinants is based on the RE-AIM framework, the project outcomes will be relevant for the future development, tailoring and implementation of ASBI in Kazakhstan. Trial registration DRKS, DRKS00015882, Registered 17 December 2018.

Abstract Background Amphetamine-type stimulants (ATS) are the second most commonly used illicit drugs in Europe and globally. However, there is limited understanding of what shapes patterns of ATS use over the life course. The ATTUNE project “Understanding Pathways to Stimulant Use: a mixed methods examination of the individual, social and cultural factors shaping illicit stimulant use across Europe” aims to fill this gap. Here we report initial findings from the life course chart exercise conducted as part of qualitative interviews with ATS users and nonusers. Methods Two hundred seventy-nine in-depth qualitative interviews were conducted with five ATS user groups (current and former dependent users;current and former frequent users;non-frequent users) and one group of exposed non-ATS users in five European countries (Germany, UK, Poland, Netherlands and Czech Republic). As part of the interviews, we used life course charts to capture key life events and substance use histories. Life events were categorised as either positive, neutral or negative, and associated data were analysed systematically to identify differences between user groups. We applied statistical analysis of variance (ANOVA) and analysis of covariance (ANCOVA) to test for group differences. Results Out of 3547 life events documented, 1523 life events were categorised as neutral, 1005 life events as positive and 1019 life events as negative. Current and formerly dependent ATS users showed more negative life events for the entire life course after age adjustment. Although some group differences could be attributed to the individuals’ life course prior to first ATS use, most negative life events were associated with periods of ATS usage. A detailed analysis of the specific life domains reveals that dominantly, the social environment was affected by negative life events. Conclusions For non-dependent, frequent and non-frequent ATS users, negative life events from the period of ATS use do not become obvious in our analysed data. Besides preventing a pathway into ATS dependency, the aim of an intervention should be to reduce the harm by for example drug testing which offers also the opportunity for interventions to prevent developing a substance use dependency. For the group of dependent ATS users, our study suggests holistic, tailored interventions and specialist treatment services are needed, as a single, simple intervention is unlikely to cover all the life domains affected.

Objective To synthesise the published literature on practitioner, patient and carer views and experiences of shared medical appointments (SMAs) for the management of long-term conditions in primary care.Design Systematic review of qualitative primary studies.Methods A systematic search was conducted using MEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCOhost), Web of Science, Social Science Premium Collection (Proquest) and Scopus (SciVerse) from database starting dates to June 2019. Practitioner, patient and carer perspectives were coded separately. Deductive coding using a framework approach was followed by thematic analysis and narrative synthesis. Quality assessment was conducted using the Critical Appraisal Skills Programme for qualitative studies.Results We identified 18 unique studies that reported practitioner (n=11), patient (n=14) and/or carer perspectivs(n=3). Practitioners reported benefits of SMAs including scope for comprehensive patient-led care, peer support, less repetition and improved efficiency compared with 1:1 care. Barriers included administrative challenges and resistance from patients and colleagues, largely due to uncertainties and unclear expectations. Skilled facilitators, tailoring of SMAs to patient groups, leadership support and teamwork were reported to be important for successful delivery. Patients’ reported experiences were largely positive with the SMAs considered a supportive environment in which to share and learn about self-care, though the need for good facilitation was recognised. Reports of carer experience were limited but included improved communication between carer and patient.Conclusion There is insufficient evidence to indicate whether views and experiences vary between staff, medical condition and/or patient characteristics. Participant experiences may be subject to reporting bias. Policies and guidance regarding best practice need to be developed with consideration given to resource requirements. Further research is needed to capture views about wider and co-occurring conditions, to hear from those without SMA experience and to understand which groups of patients and practitioners should be brought together in an SMA for best effect.PROSPERO registration number CRD42019141893.

Summary: Background: As a policy option to reduce consumption of alcohol and the harm it does, on May 1, 2018, Scotland introduced a minimum price of 50 British pence (p) per unit of alcohol (8 g) sold; Wales followed suit on March 2, 2020, with the same minimum unit price (MUP). We analysed household purchase data based on bar codes to assess the impact of these policy options in the medium term for Scotland and in the immediate term for Wales. Methods: For these location-controlled, interrupted time series regression analyses, the data source was Kantar WorldPanel's household shopping panel, which, at the time of our analysis, included 35 242 British households providing detailed information on 1·24 million separate alcohol purchases in 2015–18 and the first half of 2020. With no data exclusions, we analysed the impact of introducing MUP in Scotland, using purchases in northern England as control, and in Wales, using western England as control. The studied changes associated with MUP were price paid per gram of alcohol purchased, grams of alcohol purchased, and amount of money spent on alcohol. Findings: In Scotland, price increases and purchase decreases following the introduction of MUP in 2018 were maintained during the first half of 2020. The difference between Scotland and northern England in 2020 was a price increase of 0·741 p per gram (95% CI 0·724–0·759), a 7·6% increase, and a purchase decrease of 7·063 g per adult per household per day that an alcohol purchase was made (6·656–7·470), a 7·7% decrease. In Wales, the introduction of MUP led to similar results. The difference between Wales and western England was a price increase 0·841 of 0·841 p per gram (0·732–0·951), an 8·2% increase, and a purchase decrease of 7·052 g per adult per household per day that an alcohol purchase was made (6·463–7·640), an 8·6% decrease. For both Scotland and Wales, reductions in overall purchases of alcohol were largely restricted to households that bought the most alcohol. The introduction of MUP was not associated with an increased expenditure on alcohol by households that generally bought small amounts of alcohol and, in particular, those with low incomes. The changes were not affected by the introduction of COVID-19 confinement in the UK on March 26, 2020. Interpretation: The evidence base supporting the positive, targeted impact of MUP is strengthened by the comparable results for Scotland and Wales. The short-term impact of MUP in Scotland during 2018 is maintained during the first half of 2020. MUP is an effective alcohol policy option to reduce off-trade purchases of alcohol and should be widely considered. Funding: None.

Objective To explore the perceived reasons underlying high mortality rates among people with multiple and complex needs.Design Qualitative study using peer research.Setting North East of England.Participants Three focus group discussions were held involving (1) people with lived experience of multiple and complex needs (n=5); (2) front-line staff from health, social care and voluntary organisations that support multiple and complex needs groups (n=7); and (3) managers and commissioners of these organisations (n=9).Results Findings from this study provide valuable perspectives of people with multiple complex needs and those that provide them with support on what may be perceived factors underlying premature mortality. Mental ill health and substance misuse (often co-occurring dual diagnosis) were perceived as influencing premature mortality among multiple and complex needs groups. Perceptions of opportunities to identify people at risk included critical life events (eg, bereavement, relationship breakdown) and transitions (eg, release from prison, completion of drug treatment). Early prevention, particularly supporting young people experiencing adverse childhood experiences, was also highlighted as a priority.Conclusion High mortality in multiple and complex needs groups may be reduced by addressing dual diagnosis, providing more support at critical life events and investing in early prevention efforts. Future interventions could take into consideration the intricate nature of multiple and complex needs and improve service access and navigation.

Introduction Implementation of evidence-based care for heavy drinking and depression remains low in global health systems. We tested the impact of providing community support, training, and clinical packages of varied intensity on depression screening and management for heavy drinking patients in Latin American primary healthcare. Materials and methods Quasi-experimental study involving 58 primary healthcare units in Colombia, Mexico and Peru randomized to receive: (1) usual care (control); (2) training using a brief clinical package; (3) community support plus training using a brief clinical package; (4) community support plus training using a standard clinical package. Outcomes were proportion of: (1) heavy drinking patients screened for depression; (2) screen-positive patients receiving appropriate support; (3) all consulting patients screened for depression, irrespective of drinking status. Results 550/615 identified heavy drinkers were screened for depression (89.4%). 147/230 patients screening positive for depression received appropriate support (64%). Amongst identified heavy drinkers, adjusting for country, sex, age and provider profession, provision of community support and training had no impact on depression activity rates. Intensity of clinical package also did not affect delivery rates, with comparable performance for brief and standard versions. However, amongst all consulting patients, training providers resulted in significantly higher rates of alcohol measurement and in turn higher depression screening rates; 2.7 times higher compared to those not trained. Conclusions Training using a brief clinical package increased depression screening rates in Latin American primary healthcare. It is not possible to determine the effectiveness of community support on depression activity rates due to the impact of COVID-19.

Objective To assess the impact of new low and no alcohol beers and reformulated beers in Great Britain on household purchases of grams of alcohol.Design Interrupted time series analysis.Setting Purchase data from Kantar Worldpanel’s household shopping panel for 2015–2018.Participants 64 286 British households.Interventions Introduction of new no and low alcohol beers during 2017–2018 and reformulation of existing beers to contain less alcohol during 2018.Main outcome measures Average alcoholic strength of beer and number of grams of alcohol purchased by households.Results As assessed by British household purchase data, 46 new low and no alcohol beer products were introduced during 2015–2018, with a step-jump in volume purchased occurring at the beginning of March 2017 (event 1). During 2015–2018, 33 beer products were reformulated to contain less alcohol, with a step-jump in volume purchased occurring during mid-March 2018 (event 2). Interrupted time series analyses found a combined associated impact of both events with relative reductions of alcohol by volume of beer between 1.2% and 2.3%; purchases of grams of alcohol within beer between 7.1% and 10.2%; and purchases of grams of alcohol as a whole between 2.6% and 3.9%. The reductions were greater for reformulation than for the introduction of new low and no alcohol products. Reductions were independently higher for younger age groups of shoppers and for households that bought the most alcohol.Conclusions Even though the events were associated with significant beneficial changes, the volume of purchases of new low and no alcohol beer products (2.6% of the volume of all beers purchased during 2018) and of new reformulated beer products (6.9% of the volume of all beers purchased during 2018) was very small. This indicates that there are future opportunities to increase the volume of such products so as to reduce the harm done by alcohol.

Abstract Background Recent decades have seen rapid growth in the implementation of Electronic Medical Records (EMRs) in healthcare settings in both developed regions as well as low and middle income countries. Yet despite substantial investment, the implementation of EMRs in some primary care systems has lagged behind other settings, with piecemeal adoption of EMR functionality by primary care physicians (PCPs) themselves. We aimed to review and synthesise international literature on the attitudes of PCPs to EMR adoption using the Clinical Adoption (CA) Framework. Methods MEDLINE, PsycINFO, and EMBASE were searched from 1st January 1996 to 1st August 2017 for studies investigating PCP attitudes towards EMR adoption. Papers were screened by two independent reviewers, and eligible studies selected for further assessment. Findings were categorised against the CA Framework and the quality of studies assessed against one of three appropriate tools. Results Out of 2263 potential articles, 33 were included, based in North and South America, Europe, Middle East and Hong Kong. Concerns about the accessibility, reliability and EMR utility exerted an adverse influence on PCPs’ attitudes to adoption. However many were positive about their potential to improve clinical productivity, patient safety and care quality. Younger, computer-literate PCPs, based in large/multi-group practices, were more likely to be positively inclined to EMR use than older physicians, less-skilled in technology use, based in solo practices. Adequate training, policies and procedures favourably impacted on PCPs’ views on EMR implementation. Financial factors were common system level influencers shaping EMR adoption, from start-up costs to the resources required by ongoing use. Conclusions By using the CA Framework to synthesise the evidence, we identified a linked series of factors influencing PCPs attitudes to EMR adoption. Findings underline the need to involve end-users in future implementation programmes from the outset, to avoid the development of an EMR which is neither feasible nor acceptable for use in practice. Trial registration PROSPERO CRD42016038790.

Abstract Background Despite robust evidence for their effectiveness, it has proven difficult to translate alcohol prevention activities into routine health care practice. Previous research has identified numerous provider-level barriers affecting implementation, but these have been less extensively investigated in the wider population. We sought to: (1) investigate patients’ beliefs and attitudes to being asked about alcohol consumption in health care; and (2) identify the characteristics of those who are supportive of addressing alcohol consumption in health care. Methods Cross-sectional household interviews conducted as part of the national Alcohol Toolkit Study in England between March and April 2017. Data were collected on age, gender, social grade, drinking category, and beliefs and attitudes to being asked about alcohol in routine health care. Unadjusted and multivariate-adjusted logistic regression models were performed to investigate associations between socio-demographic characteristics and drinking category with being “pro-routine” (i.e. ‘agree completely’ that alcohol consumption should be routinely addressed in health care) or “pro-personal” (i.e. ‘agree completely’ that alcohol is a personal matter and not something health care providers should ask about). Results Data were collected on 3499 participants, of whom 50% were “pro-routine” and 10% were “pro-personal”. Those in social grade C1, C2, D and E were significantly less likely than those in AB of being “pro-routine”. Women were less likely than men to be “pro-personal”, and those aged 35–44 or 65 years plus more likely to be “pro-personal” compared with participants aged 16–24. Respondents aged 65 plus were twice as likely as those aged 16–24 to agree completely that alcohol consumption is a personal matter and not something health care providers should ask about (OR 2.00, 95% CI 1.34–2.99). Conclusions Most adults in England agree that health care providers should routinely ask about patients’ alcohol consumption. However, older adults and those in lower socio-economic groups are less supportive. Drinking status appears to have limited impact on whether people believe that alcohol is a personal matter and not something health care providers should ask about. Registration Open Science Framework (https://osf.io/xn2st/).

Introduction Excessive drinking and depression are frequently comorbid and make a substantial contribution to the global non-communicable disease burden. A range of effective interventions and treatments exist for either excessive drinking or depression alone, including a positive emerging evidence base for the use of digital interventions. Computerised and/or smartphone delivered advice could provide flexible, coordinated support for patients with comorbid excessive drinking and depression. However, to date, no systematic review of the evidence has been conducted focused on the effectiveness of digital interventions for this specific comorbid population. This systematic review will identify and evaluate the effectiveness of digital interventions for reducing comorbid excessive drinking and depression in community-dwelling populations.Methods and analysis We will search MEDLINE, The Cochrane Library, CENTRAL, CINAHL, PsycINFO, ERIC and SCI from inception to end of July 2019 for randomised controlled trials that evaluate any personalised digital intervention for comorbid excessive drinking and depression and published in any language. Primary outcomes will be changes in quantity of alcohol consumed and depressive symptoms. Screening, data extraction and risk of bias assessment will be undertaken independently by two reviewers, with disagreements resolved through discussion. Meta-analytic methods will be used to synthesise the data collected relating to the primary outcomes of interest.Ethics and dissemination As a systematic review, ethical approval is not needed. Findings will be published in peer-reviewed journals and presented at conferences.Trial registration number CRD42019130134.

Introduction Amphetamine-type stimulants (ATS) including amphetamine, methylenedioxymethamphetamine/‘ecstasy’, methamphetamine, synthetic cathinones and ‘Ritalin’ are the second most commonly used illicit drugs globally. Yet, there is little evidence on which factors are associated with the development of different patterns of ATS use over the life course. This study aims to examine which individual, social and environmental factors shape different pathways and trajectories of ATS consumption. The study will be conducted in five European countries: Germany, the Netherlands, Poland, Czech Republic and the UK.Methods and analysis We will use a sequential mixed-methods study design to investigate the multiple factors (familial, social and occupational situation, critical life events, general risk behaviour, mental and physical health, satisfaction with life) that shape individual ATS use pathways. A systematic literature review will be performed to provide an overview of the current academic literature on the topic. In module 1, qualitative semistructured interviews (n=ATS users and non-users) will be conducted to explore individual experiences of, and perspectives on, dynamics of change in stimulant consumption patterns. In module 2, structured questionnaires (n=2000 ATS users and non-users) will be administered via tablet computers to validate and enhance the generalisability of the interview findings. Data integration will take place at two key points. First, during the study, where the findings from the first qualitative interviews will inform the design of the structured questionnaire. Second, at the end of the study, where mixed methods data will be brought together to generate an in-depth, contextualised understanding of the research topic.Ethics and dissemination The study has been approved by the respective responsible ethics committee in each participating country. Data will be treated confidentially to ensure participants’ anonymity. Findings will be disseminated in peer-reviewed scientific journals, national and international conferences, and in briefings for policy and practice.

BACKGROUND:Concurrent alcohol and medication use can result in significant problems especially in mid to later life. Alcohol is often used instead of medication for a number of health-related conditions. This novel qualitative study explored concurrent alcohol and medication use, as well as the use of alcohol for medicinal purposes, in a sample of individuals in mid to later life. METHODS:Twenty-four interviews (12 men/12 women, ages 51-90 years) and three focus groups (n = 27, 6 men/21 women, ages 50-95 years) from three branches of Age UK and two services for alcohol problems in North East England. RESULTS:Older people in this study often combined alcohol and medication, frequently without discussing this with their family doctor. However, being prescribed medication could act as a motivating factor to stop or reduce alcohol consumption. Participants also used alcohol to self-medicate, to numb pain, aid sleep or cope with stress and anxiety. Some participants used alcohol to deal with depression although alcohol was also reported as a cause of depression. Women in this study reported using alcohol to cope with mental health problems while men were more likely to describe reducing their alcohol consumption as a consequence of being prescribed medication. CONCLUSIONS:As older people often combine alcohol and medication, health professionals such as family doctors, community nurses, and pharmacists should consider older patients' alcohol consumption prior to prescribing or dispensing medication and should monitor subsequent drinking. In particular, older people should be informed of the dangers of concurrent alcohol and medication use.

This paper considers the ethical and practical issues of recruiting for, and administering a quantitative survey with marginalised populations. These issues were identified through a focus group discussion, which consolidated and expanded upon informal conversations held previously by five researchers about their experiences of conducting a face-to-face survey (using predominantly quantitative questions) with people who used amphetamine type substances in North East England, UK. Inductive and deductive thematic analysis of the focus group discussion led to the generation of three key themes: researcher positionality, emotions, and role dilemmas; study design; and ethics in practice. This paper therefore aims to extend literature which explores ethical and practical issues involved in studies with marginalised populations. It makes methodological suggestions for how work across a range of disciplines could make face-to-face survey research, and future studies with marginalised populations, more inclusive for both participants and researchers.

Background: Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP – hyperemesis gravidarum (HG) – affects 0.3–1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG. Objectives: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG. Data sources: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. Obstetric Medicine was hand-searched, as were websites of relevant organisations. Costs came from NHS sources. Review methods: A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments. Results: Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder (n = 20) it was unclear. The non-randomised studies (n = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo (n = 12); steroid versus usual treatment (n = 7); ginger versus placebo (n = 6); ginger versus vitamin B6 (n = 6); and vitamin B6 versus placebo (n = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. Limitations: The main limitations were the quantity and quality of the data available. Conclusion: There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed. Study registration: This study is registered as PROSPERO CRD42013006642. Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Approximately 33% of 15- to 16-year-olds in England report alcohol intoxication in the past month. This present work builds on the evidence base by focusing on Alcohol Screening and Brief Intervention (ASBI) to reduce hazardous drinking in younger adolescents. Objectives: To explore the feasibility and acceptability of a future definitive cluster randomised controlled trial (cRCT) of ASBI in a school setting to staff, young people and parents; to explore the fidelity of the interventions as delivered by school learning mentors; to estimate the parameters for the design of a definitive cRCT of brief alcohol intervention, including rates of eligibility, consent, participation and retention at 12 months; and to pilot the collection of cost and resource-use data to inform the cost-effectiveness/utility analysis in a definitive trial. Setting: Seven schools across one geographical area in North East England. Methods: Feasibility of trial processes, recruitment and retention and a qualitative evaluation examined facilitators and barriers to the use of ASBI approaches in the school setting in this age group. A three-arm pilot cRCT (with randomisation at the school level) with qualitative evaluation to assess the feasibility of a future definitive cRCT of the effectiveness and cost-effectiveness of ASBI in a school setting, with an integrated qualitative component. The trial ran in parallel with a repeated cross-sectional survey, which facilitated screening for the trial. Participants: Year 10 school pupils (aged 14–15 years). Interventions: Young people who screened positive on a single alcohol screening question, and consented to take part, were randomised to one of three groups: (1) feedback that their drinking habits may be risky and provision of an advice leaflet (control condition, n = two schools); (2) feedback as for the control condition plus a 30-minute brief interactive session, which combined structured advice and motivational interviewing techniques, delivered by the school learning mentor (intervention 1, n = two schools); or (3) feedback as for the control condition plus a 30-minute brief interactive session as for intervention 1 plus a 60-minute session involving family members delivered by the school learning mentor (intervention 2, n = three schools). Young people were followed up at 12 months. Main outcome measures: Feasibility and acceptability. Randomisation: Randomisation was carried out at the school level. Randomisation achieved balance on two school-level variables (numbers of pupils in school year and proportion receiving free school meals). Blinding: School staff, young people and researchers were not blind to the intervention allocated. Results: A total of 229 young people were eligible for the trial; 182 (79.5%) were randomised (control, n = 53; intervention 1, n = 54; intervention 2, n = 75). Of the 75 randomised to intervention 2, 67 received intervention 1 (89%). Eight received both intervention 1 and intervention 2 (11%). In total, 160 out of 182 were successfully followed up at 12 months (88%). Interviews were carried out with six school lead liaisons, 13 learning mentors, 27 young people and seven parents (n = 53). Analysis shows that the school setting is a feasible and acceptable place to carry out ASBI, with learning mentors seen as suitable people to do this. Intervention 2 was not seen as feasible or acceptable by school staff, parents or young people. Outcomes/conclusions: It is feasible and acceptable to carry out a trial of the effectiveness and cost-effectiveness of single-session ASBI with young people in the school setting, with learning mentors delivering the intervention. Future work should include a definitive study that does not include a parental arm. Trial registration: Current Controlled Trials ISRCTN07073105. Funding: The National Institute for Health Research Public Health Research programme.

Background: While primary health care (PHC)-based prevention and management of heavy drinking is clinically effective and cost-effective, it remains poorly implemented in routine practice. Systematic reviews and multi-country studies have demonstrated the ability of training and support programmes to increase PHC-based screening and brief advice activity to reduce heavy drinking. However, gains have been only modest and short term at best. WHO studies have concluded that a more effective uptake could be achieved by embedding PHC activity within broader community and municipal support. Protocol: A quasi-experimental study will compare PHC-based prevention and management of heavy drinking in three intervention cities from Colombia, Mexico and Peru with three comparator cities from the same countries. In the implementation cities, primary health care units (PHCUs) will receive training embedded within ongoing supportive municipal action over an 18-month implementation period. In the comparator cities, practice as usual will continue at both municipal and PHCU levels. The primary outcome will be the proportion of consulting adult patients intervened with (screened and advice given to screen positives). The study is powered to detect a doubling of the outcome measure from an estimated 2.5/1,000 patients at baseline. Formal evaluation points will be at baseline, mid-point and end-point of the 18-month implementation period. We will present the ratio (plus 95% confidence interval) of the proportion of patients receiving intervention in the implementation cities with the proportions in the comparator cities. Full process evaluation will be undertaken, coupled with an analysis of potential contextual, financial and political-economy influencing factors. Discussion: This multi-country study will test the extent to which embedding PHC-based prevention and management of alcohol use disorder with supportive municipal action leads to improved scale-up of more patients with heavy drinking receiving appropriate advice and treatment. Study status: The four-year study will start on 1 st December 2017.

Background: While primary health care (PHC)-based prevention and management of alcohol use disorder (AUD) is clinically effective and cost-effective, it remains poorly implemented in routine practice. Systematic reviews and multi-country studies have demonstrated the ability of training and support programmes to increase PHC-based screening and brief advice activity to reduce heavy drinking. However, gains have been only modest and short term at best. WHO studies have concluded that a more effective uptake could be achieved by embedding PHC activity within broader community and municipal support. Protocol: A quasi-experimental study will compare PHC-based prevention and management of AUD, operationalized by heavy drinking, in three intervention cities from Colombia, Mexico and Peru with three comparator cities from the same countries. In the implementation cities, primary health care units (PHCUs) will receive training embedded within ongoing supportive municipal action over an 18-month implementation period. In the comparator cities, practice as usual will continue at both municipal and PHCU levels. The primary outcome will be the proportion of consulting adult patients intervened with (screened and advice given to screen positives). The study is powered to detect a doubling of the outcome measure from an estimated 2.5/1,000 patients at baseline. Formal evaluation points will be at baseline, mid-point and end-point of the 18-month implementation period. We will present the ratio (plus 95% confidence interval) of the proportion of patients receiving intervention in the implementation cities with the proportions in the comparator cities. Full process evaluation will be undertaken, coupled with an analysis of potential contextual, financial and political-economy influencing factors. Discussion: This multi-country study will test the extent to which embedding PHC-based prevention and management of alcohol use disorder with supportive municipal action leads to improved scale-up of more patients with heavy drinking receiving appropriate advice and treatment.

Background: While primary health care (PHC)-based prevention and management of alcohol use disorder (AUD) is clinically effective and cost-effective, it remains poorly implemented in routine practice. Systematic reviews and multi-country studies have demonstrated the ability of training and support programmes to increase PHC-based screening and brief advice activity to reduce heavy drinking. However, gains have been only modest and short term at best. WHO studies have concluded that a more effective uptake could be achieved by embedding PHC activity within broader community and municipal support. Protocol: A quasi-experimental study will compare PHC-based prevention and management of AUD, operationalized by heavy drinking, in three intervention cities from Colombia, Mexico and Peru with three comparator cities from the same countries. In the implementation cities, primary health care units (PHCUs) will receive training embedded within ongoing supportive municipal action over an 18-month implementation period. In the comparator cities, practice as usual will continue at both municipal and PHCU levels. The primary outcome will be the proportion of consulting adult patients intervened with (screened and advice given to screen positives). The study is powered to detect a doubling of the outcome measure from an estimated 2.5/1,000 patients at baseline. Formal evaluation points will be at baseline, mid-point and end-point of the 18-month implementation period. We will present the ratio (plus 95% confidence interval) of the proportion of patients receiving intervention in the implementation cities with the proportions in the comparator cities. Full process evaluation will be undertaken, coupled with an analysis of potential contextual, financial and political-economy influencing factors. Discussion: This multi-country study will test the extent to which embedding PHC-based prevention and management of alcohol use disorder with supportive municipal action leads to improved scale-up of more patients with heavy drinking receiving appropriate advice and treatment.