Incidence of Clostridioides difficile infection (CDI) related to antibiotic prescribing by GP surgeries in Wales.

BACKGROUND: Clostridioides difficile infection (CDI) is a healthcare-acquired infection (HAI) causing significant morbidity and mortality. Welsh CDI rates are high in comparison with those in England and Scotland. OBJECTIVES: This retrospective ecological study used aggregated disease surveillance data to understand the impact of total and high-risk Welsh GP antibiotic prescribing on total and stratified inpatient/non-inpatient CDI incidence. METHODS: All cases of confirmed CDI, during the financial years 2014-15 to 2017-18, were linked to aggregated rates of antibiotic prescribing in their GP surgery and classified as 'inpatient', 'non-inpatient' or 'unknown' by Public Health Wales. Multivariable negative-binomial regression models, comparing CDI incidence with antibiotic prescribing rates, were adjusted for potential confounders: location; age; social deprivation; comorbidities (estimated from prevalence of key health indicators) and proton pump inhibitor (PPI) prescription rates. RESULTS: There were 4613 confirmed CDI cases, with an incidence (95% CI) of 1.44 (1.40-1.48) per 1000 registered patients. Unadjusted analysis showed that an increased risk of total CDI incidence was associated with higher total antibiotic prescribing [relative risk (RR) (95% CI) = 1.338 (1.170-1.529) per 1000 items per 1000 specific therapeutic group age-sex related GP prescribing units (STAR-PU)] and that high-risk antibiotic classes were positively associated with total CDI incidence. Location, age ≥65 years and diabetes were associated with increased risk of CDI. After adjusting for confounders, prescribing of clindamycin showed a positive association with total CDI incidence [RR (95% CI) = 1.079 (1.001-1.162) log items per 1000 registered patients]. CONCLUSIONS: An increased risk of CDI is demonstrated at a primary care practice population level, reflecting their antibiotic prescribing rates, particularly clindamycin, and population demographics.

Reweighting national survey data for small area behaviour estimates: modelling alcohol consumption in Local Authorities in England.

BACKGROUND: There are likely to be differences in alcohol consumption levels and patterns across local areas within a country, yet survey data is often collected at the national or sub-national/regional level and is not representative for small geographic areas. METHODS: This paper presents a method for reweighting national survey data-the Health Survey for England-by combining survey and routine data to produce simulated locally representative survey data and provide statistics of alcohol consumption for each Local Authority in England. RESULTS: We find a 2-fold difference in estimated mean alcohol consumption between the lightest and heaviest drinking Local Authorities, a 4.5-fold difference in abstention rates, and a 3.5-fold difference in harmful drinking. The method compares well to direct estimates from the data at regional level. CONCLUSIONS: The results have important policy implications in itself, but the reweighted data can also be used to model local policy effects. This method can also be used for other public health small area estimation where locally representative data are not available.

High response and re-infection rates among people who inject drugs treated for hepatitis C in a community needle and syringe programme.

To achieve WHO hepatitis C virus (HCV) elimination targets by 2030, mathematical models suggest there needs to be significant scale-up of treatment among people who inject drugs (PWID). We tested whether people who actively inject drugs can be recruited and treated successfully through a community needle and syringe programme (NSP), and assessed rates of re-infection. 105 HCV RNA positive participants were enrolled prospectively. Participants were recruited from the largest NSP in Dundee over 42 months. 94/105 individuals commenced treatment. Genotype 1 (G1) individuals (n = 37) were treated with peg-interferon+ribavirin+Simepravir/Telaprevir. Genotype 2/3 (G2/3) (n = 57) received peg-interferon+ribavirin. Weekly study visits took place within the NSP. Mean age of participants was 34.0 years (SD 6.9), 71.3% (61/94) were male. One in five (20/94) participants were homeless. 68.1% (64/94) were on OST (opiate substitution therapy) at enrolment; participants injected median 6.5 times/wk. In terms of clinical outcomes, >80% treatment adherence was 71.3% (67/94). There was no difference in SVR-12 rates by genotype: 81.0% (30/37) for G1 and 82.5% (47/55) for G2/3. At 18 months post-treatment, 15/77 participants were reinfected, followed up over 69.8 person-years, yielding a re-infection rate of 21.5/100 person-years (95% CI 13.00-35.65). This trial demonstrates that HCV treatment can be delivered successfully to the target population of treatment as prevention strategies. We report higher rates of re-infection than existing estimates among PWID. Scale-up of HCV treatment should be pursued alongside a comprehensive programme of harm reduction interventions to help minimize re-infection and reduce HCV transmission.

Hepatitis C elimination among people who inject drugs: Challenges and recommendations for action within a health systems framework.

The burden of hepatitis C infection is considerable among people who inject drugs (PWID), with an estimated prevalence of 39%, representing an estimated 6.1 million people who have recently injected drugs living with hepatitis C infection. As such, PWID are a priority population for enhancing prevention, testing, linkage to care, treatment and follow-up care in order to meet World Health Organization (WHO) hepatitis C elimination goals by 2030. There are many barriers to enhancing hepatitis C prevention and care among PWID including poor global coverage of harm reduction services, restrictive drug policies and criminalization of drug use, poor access to health services, low hepatitis C testing, linkage to care and treatment, restrictions for accessing DAA therapy, and the lack of national strategies and government investment to support WHO elimination goals. On 5 September 2017, the International Network of Hepatitis in Substance Users (INHSU) held a roundtable panel of international experts to discuss remaining challenges and future priorities for action from a health systems perspective. The WHO health systems framework comprises six core components: service delivery, health workforce, health information systems, medical procurement, health systems financing, and leadership and governance. Communication has been proposed as a seventh key element which promotes the central role of affected community engagement. This review paper presents recommended strategies for eliminating hepatitis C as a major public health threat among PWID and outlines future priorities for action within a health systems framework.

Cannabis use and the risk of tuberculosis: a systematic review.

BACKGROUND: Cannabis has been identified as a possible risk factor in some tuberculosis (TB) outbreaks. As the most widely used (largely) illegal substance in Western countries this may be an important public health concern. We aim to systematically review the evidence on the association between cannabis use and TB (latent infection and active disease) to inform ongoing and future TB prevention and control strategies. METHODS: We conducted a systematic review. We searched Ovid Medline, Embase and PsycInfo, together with the World Health Organization website and Google Scholar, for all years to January 2018. Reference lists and conference abstracts were hand-searched, a forward citation search was conducted on the Web of Science, and experts were contacted. Two authors independently screened studies for inclusion, extracted data and assessed risk of bias using an adapted version of ROBINS-I ("Risk of Bias in Non-randomised Studies - of Interventions"). Data were narratively synthesised. RESULTS: Of 377 records identified, 11 studies were eligible. Study designs were heterogeneous. Six studies utilised a relevant comparator group. Four of these investigated the association between cannabis use and latent TB infection; all provided some evidence of an association, although only two of these had adjusted for confounders. The remaining two comparator studies investigated the association between cannabis use and active TB disease; neither found evidence of an association after adjusting for confounding. All six studies were at "Serious" risk of bias. The five studies which did not utilise a relevant comparator group were all indicative of TB outbreaks occurring among cannabis users, but the quality of the evidence was very weak. CONCLUSIONS: Evidence for an association between cannabis use and TB acquisition is weak. The topic warrants further robust primary research including the collection of consistent and accurate exposure information, including cannabis use practices, dose and frequency, and adjustment for confounders.

Alcohol Use in Adolescence and Later Working Memory: Findings From a Large Population-Based Birth Cohort.

AIMS: The study aimed to examine the association between adolescent alcohol use and working memory (WM) using a large population sample. METHODS: Data from the Avon Longitudinal Study of Parents and Children were used to investigate the association between alcohol use at age 15 years and WM 3 years later, assessed using the N-back task (N ~ 3300). A three-category ordinal variable captured mutually exclusive alcohol groupings ranging in order of severity (i.e. low alcohol users, frequent drinkers and frequent/binge drinkers). Differential dropout was accounted for using multiple imputation and inverse probability weighting. Adjustment was made for potential confounders. RESULTS: There was evidence of an association between frequent/binge drinking (compared to the low alcohol group) and poorer performance on the 3-back task after adjusting for sociodemographic confounding variables, WM at age 11 years, and experience of a head injury/unconsciousness before age 11 years (ß = -0.23, 95% CI = -0.37 to -0.09, P = 0.001). However, this association was attenuated (ß = -0.12, 95% CI = -0.27 to 0.03, P = 0.11) when further adjusted for baseline measures of weekly cigarette tobacco and cannabis use. Weaker associations were found for the less demanding 2-back task. We found no evidence to suggest frequent drinking was associated with performance on either task. CONCLUSIONS: We found weak evidence of an association between sustained heavy alcohol use in mid-adolescence and impaired WM 3 years later. Although we cannot fully rule out the possibility of reverse causation, several potential confounding variables were included to address the directionality of the relationship between WM and alcohol use problems.

Investigating local policy drivers for alcohol harm prevention: a comparative case study of two local authorities in England.

BACKGROUND: The considerable challenges associated with implementing national level alcohol policies have encouraged a renewed focus on the prospects for local-level policies in the UK and elsewhere. We adopted a case study approach to identify the major characteristics and drivers of differences in the patterns of local alcohol policies and services in two contrasting local authority (LA) areas in England. METHODS: Data were collected via thirteen semi-structured interviews with key informants (including public health, licensing and trading standards) and documentary analysis, including harm reduction strategies and statements of licensing policy. A two-stage thematic analysis was used to categorize all relevant statements into seven over-arching themes, by which document sources were then also analysed. RESULTS: Three of the seven over-arching themes (drink environment, treatment services and barriers and facilitators), provided for the most explanatory detail informing the contrasting policy responses of the two LAs: LA1 pursued a risk-informed strategy via a specialist police team working proactively with problem premises and screening systematically to identify riskier drinking. LA2 adopted a more upstream regulatory approach around restrictions on availability with less emphasis on co-ordinated screening and treatment measures. CONCLUSION: New powers over alcohol policy for LAs in England can produce markedly different policies for reducing alcohol-related harm. These difference are rooted in economic, opportunistic, organisational and personnel factors particular to the LAs themselves and may lead to closely tailored solutions in some policy areas and poorer co-ordination and attention in others.

Childhood internalizing symptoms are negatively associated with early adolescent alcohol use.

BACKGROUND: The relationship between childhood internalizing problems and early adolescent alcohol use has been infrequently explored and remains unclear. METHODS: We employed growth mixture modeling of internalizing symptoms for a large, population-based sample of U.K. children (the Avon Longitudinal Study of Parents and Children Cohort) to identify trajectories of childhood internalizing symptoms from age 4 through age 11.5. We then examined the relationship between membership in each trajectory and alcohol use in early adolescence (reported at age 13.8). RESULTS: Overall, children experiencing elevated levels of internalizing symptoms were less likely to use alcohol in early adolescence. This finding held true across all internalizing trajectories; that is, those exhibiting increasing levels of internalizing symptoms over time, and those whose symptoms desisted over time, were both less likely to use alcohol than their peers who did not exhibit internalizing problems. CONCLUSIONS: We conclude that childhood internalizing symptoms, unlike adolescent symptoms, are negatively associated with early adolescent alcohol experimentation. Additional studies are warranted to follow up on our preliminary evidence that symptoms of phobia and separation anxiety drive this effect.

Dimensions of parental alcohol use/problems and offspring temperament, externalizing behaviors, and alcohol use/problems.

BACKGROUND: Alcohol consumption (AC) and alcohol problems (AP) are complex traits. How many factors reflecting parental AC and AP are present in the large prospectively followed Avon Longitudinal Study of Parents and Children cohort? Would these factors be uniquely associated with various temperamental and alcohol-related outcomes in the children? METHODS: We factor-analyzed multiple items reflecting maternal and paternal AC and AP measured over a 12-year period from before the birth of the child (n = 14,093 families). We examined, by linear regression controlling for socioeconomic status, the relationship between scales derived from these factors and offspring early childhood temperament, externalizing traits, and adolescent AC and AP (ns ranging from 9,732 to 3,454). RESULTS: We identified 5 coherent factors: typical maternal AC, maternal AC during pregnancy, maternal AP, paternal AC, and paternal AP. In univariate analyses, maternal and paternal AC and AP were modestly and significantly associated with low shyness, sociability, hyperactivity, and conduct problems in childhood and early adolescence; delinquent behavior at age 15; and AC and AP at ages 15 and 18. AC and AP at age 18 were more strongly predicted by parental factors than at age 15. Maternal AC during pregnancy uniquely predicted externalizing traits at ages 4, 13, and 15. CONCLUSIONS: Parental AC and AP are complex multidimensional traits that differ in their association with a range of relevant measures in their children. Controlling for background AC and AP, self-reported levels of maternal AC during pregnancy uniquely predicted externalizing behaviors in childhood and adolescence.

Adolescent alcohol use is predicted by childhood temperament factors before age 5, with mediation through personality and peers.

BACKGROUND: Very few studies chart developmental pathways from early childhood to adolescent alcohol-related outcomes. We test whether measures of temperament collected from mothers at multiple assessments from 6 months through 5 years predict alcohol-related outcomes in mid-adolescence, the developmental pathways that mediate these effects, and whether there are gender differences in pathways of risk. METHODS: Structural models were fit to longitudinal data from the Avon Longitudinal Study of Parents and Children, an epidemiological sample of pregnant women with delivery dates between April 1991 and December 1992, with children followed longitudinally. Temperamental characteristics were assessed at 6 time points from 6 to 69 months of age. Alcohol use and problems were assessed at age 15.5. Analyses here utilize data from 6,504 boys and 6,143 girls. RESULTS: Childhood temperament prior to age 5 predicted adolescent alcohol use and problems at age 15.5 years, even after controlling for socio-demographic factors and parental alcohol problems. In both boys and girls, 2 largely uncorrelated and distinct temperament styles-children who were rated as having consistent emotional and conduct difficulties through age 5, and children who were rated as consistently sociable through age 5-both showed elevated rates of alcohol problems at age 15.5, but via different mediational pathways. In both genders, the association between emotional and conduct difficulties and alcohol problems was mediated through reduced conscientiousness and lower emotional stability. The association between sociability and alcohol problems was mediated through increased extraversion and sensation-seeking for both genders. Boys also showed mediation for sociability and alcohol outcomes through friendship characteristics, and girls through lower conscientiousness and reduced emotional stability. CONCLUSIONS: Our findings support multiple pathways to alcohol consumption and problems in adolescence. Some of these pathways are shared in boys and girls, while other risk factors are more salient in one gender or the other.

Use of core modification in the discovery of CC214-2, an orally available, selective inhibitor of mTOR kinase.

We report here the discovery of a novel series of selective mTOR kinase inhibitors and the identification of CC214-2, a compound with demonstrated anti-tumor activity upon oral dosing in a PC3 prostate cancer xenograft model. A series of 4,6-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones were discovered through a core modification of our original compound series. Analogs from this series have excellent mTOR potency and maintain selectivity over the related PI3Kα lipid kinase. Compounds such as CC214-2 were found to block both mTORC1(pS6) and mTORC2(pAktS473) signaling in PC3 cancer cells, in vitro and in vivo.

Development of a Brief Intervention for Emergency Department Attendees Presenting With Self-Harm and Co-Occurring Substance Use Problems.

Background: People who present to the emergency department with self-harm and co-occurring substance use problems often have difficulty accessing effective care. Aims: To develop a brief psychosocial intervention for this population, which would be suitable for testing in a future randomized controlled trial. Methods: A modified Delphi method was used. A 34-item, 3-round, online Delphi survey was informed by a literature review and stakeholder telephone discussions (n = 17). Two panels consisting of people with lived experience (PWLE: n = 15) and people with occupational experience (PWOE: n = 21) participated in the survey. The threshold for consensus was a pooled agreement rate across the two panels of 80% or more. Results: Expert consensus was achieved for 22 items. The new intervention consists of weekly follow-up phone calls for up to 1 month, delivered by Liaison Psychiatry practitioners, in which both self-harm and substance use problems are explored and addressed, and patients are supported in accessing community services. Limitations: Some stakeholder ideas regarding intervention components could not be included as survey options due to anticipated difficulties with implementation. Conclusions: The key elements of a brief psychosocial intervention for self-harm and co-occurring substance use problems have been agreed. Feasibility testing is currently underway.

Practitioner and digitally delivered interventions for reducing hazardous and harmful alcohol consumption in people not seeking alcohol treatment: a systematic review and network meta-analysis.

AIM: To compare the effectiveness of practitioner versus digitally delivered interventions for reducing hazardous and harmful alcohol consumption. DESIGN: Systematic review and network meta-analysis comprising comprehensive search for randomised controlled trials, robust screening and selection methods and appraisal with the Cochrane Risk of Bias tool. Network meta-analyses were conducted in Stata using random effects, frequentist models. The confidence in network meta-analysis (CINeMA) tool was used to assess confidence in effect sizes. SETTING: Online or community or health settings where the intervention was immediately accessible without referral. PARTICIPANTS: Non treatment-seeking hazardous or harmful drinkers. MEASUREMENTS: Primary outcome was mean difference in alcohol consumption (g/wk); secondary outcome was number of single high intensity drinking episodes. Baseline consumption was analysed as a covariate. FINDINGS: Of 201 included trials (94 753 participants), 152 reported a consumption outcome that could be converted to grams/week; 104 reported number of single high intensity drinking episodes. At 1 and 6 months, practitioner delivered interventions reduced consumption more than digitally delivered interventions (1 month: -23 g/wk (95% CI, -43 to -2); 6 months: -14 g/wk [95% CI, -25 to -3]). At 12 months there was no evidence of difference between practitioner and digitally delivered interventions (-6 g/wk [95% CI, -24 to 12]). There was no evidence of a difference in single high intensity drinking episodes between practitioner and digitally delivered interventions at any time point. Effect sizes were small, but could impact across a population with relatively high prevalence of hazardous and harmful drinking. Heterogeneity was a concern. Some inconsistency was indicated at 1 and 6 months, but little evidence was apparent at 12 months. CONCLUSION: Practitioner delivered interventions for reducing hazardous and harmful alcohol consumption are more effective than digitally delivered interventions up to 6 months; at 12 months there is no evidence of a difference.

The effectiveness of psychosocial interventions at reducing the frequency of alcohol and drug use in parents: findings of a Cochrane Review and meta-analyses.

BACKGROUND AND AIM: Parental substance use is a major public health and safeguarding concern. There have been a number of trials examining interventions targeting this risk factor. We aimed to estimate the effectiveness of psychosocial interventions at reducing parental substance use. DESIGN: We used systematic methods to identify trials; pooling data using a random-effects model. Moderator analyses examined influence of parent gender, presence of child in treatment and intervention type. SETTING: No restrictions on setting. PARTICIPANTS: Substance using parents of children below the age of 21 years. INTERVENTIONS: Psychosocial interventions including those that targeted drug and alcohol use only, and drug and alcohol use in combination with associated issues. MEASUREMENTS: Frequency of alcohol use and frequency of drug use. FINDINGS: We included eight unique studies with a total of 703 participants. Psychosocial interventions were more effective at reducing the frequency of parental alcohol use than comparison conditions at 6-month [standardized mean difference (SMD) = - 0.32, 95% confidence interval (CI) = -0.51 to -0.13, P = 0.001] and 12-month follow-up (SMD = -0.25, 95% CI = -0.47 to -0.03, P = 0.02) and frequency of parental drug use at 12 months only (SMD = -0.21, 95% CI = -0.41 to -0.01, P = 0.04). Integrated interventions which combined both parenting and substance use targeted components were effective at reducing the frequency of alcohol use (6 months: SMD = -0.56, 95% CI = -0.96 to -0.016, P = 0.006; 12 months: SMD = -0.42, 95% CI = -0.82 to -0.03, P = 0.04) and drug use (6 months: SMD = -0.39, 95% CI = -0.75 to -0.03, P = 0.04; 12 months: SMD = -0.43, 95% CI = -0.80 to -0.07, P = 0.02). Interventions targeting only substance use or parenting skills were not effective at reducing frequency of alcohol or drug use at either time-point. CONCLUSION: Psychosocial interventions should target both parenting and substance use in an integrated intervention.

Interventions to prevent HIV and Hepatitis C among people who inject drugs: Latest evidence of effectiveness from a systematic review (2011 to 2020).

BACKGROUND: Hepatitis C virus (HCV) and HIV remain prevalent among people who inject drugs (PWID) and transmission is usually associated with injecting risk behaviour (IRB). We update a 2011 review of reviews (RoR) to assess the latest evidence on the effectiveness of harm reduction interventions - drug treatment (including opioid agonist therapy [OAT]), needle and syringe programmes (NSP) and other interventions - in the prevention of HCV and HIV transmission, and related measures of infection risk (IRB and injecting frequency [IF]), among PWID. METHODS: We undertook an initial search for systematic reviews (i.e. an Overview of Reviews [OoR]) and subsequent systematic searches for primary studies where required. Where there was sufficient evidence based on synthesis of multiple robust studies for an intervention effect in the 2011 RoR, new evidence was not sought. Medline, CINAHL, The Cochrane Library, EMBASE, PsycINFO and Web of Science were searched (2011-2020). Two reviewers screened papers, extracted data, and graded reviews/studies. We classified evidence as 'sufficient', 'tentative', 'insufficient', or 'no evidence'. RESULTS: We screened 8513 reviews and 7133 studies, with 27 and 61 identified as relevant, respectively. The level of evidence increased since the 2011 RoR and is now 'sufficient' for OAT (regarding all outcomes), NSP (for reducing HIV transmission and IRB), and combination OAT/NSP (for reducing HCV transmission). There is also now sufficient evidence for in-prison OAT, psychosocial interventions, pharmacy-based NSP and provision of sterile drug preparation equipment for reducing IRB. CONCLUSION: There is now a strong body of empirical evidence for the effectiveness of OAT and NSP, alone and in combination, in reducing IRB, and HCV and HIV transmission. However, there is still a relative lack of evidence for other interventions, including heroin-assisted treatment, pharmacological treatment for stimulant dependence, contingency management, technology-based interventions, low dead space syringes and drug consumption rooms on HCV or HIV risk.

Prevention of HIV infection for people who inject drugs: why individual, structural, and combination approaches are needed.

HIV can spread rapidly between people who inject drugs (through injections and sexual transmission), and potentially the virus can pass to the wider community (by sexual transmission). Here, we summarise evidence on the effectiveness of individual-level approaches to prevention of HIV infection; review global and regional coverage of opioid substitution treatment, needle and syringe programmes, and antiretroviral treatment; model the effect of increased coverage and a combination of these three approaches on HIV transmission and prevalence in injecting drug users; and discuss evidence for structural-level interventions. Each intervention alone will achieve modest reductions in HIV transmission, and prevention of HIV transmission necessitates high-coverage and combined approaches. Social and structural changes are potentially beneficial components in a combined-intervention strategy, especially when scale-up is difficult or reductions in HIV transmission and injection risk are difficult to achieve. Although further evidence is needed on how to optimise combinations of interventions in different settings and epidemics, we know enough now about which actions are effective: the challenge is to deliver these well and to scale.

Discovery and SAR exploration of a novel series of imidazo[4,5-b]pyrazin-2-ones as potent and selective mTOR kinase inhibitors.

We report here the discovery of a novel series of selective mTOR kinase inhibitors. A series of imidazo[4,5-b]pyrazin-2-ones, represented by screening hit 1, was developed into lead compounds with excellent mTOR potency and exquisite kinase selectivity. Potent compounds from this series show >1000-fold selectivity over the related PI3Kα lipid kinase. Further, compounds such as 2 achieve mTOR pathway inhibition, blocking both mTORC1 and mTORC2 signaling, in PC3 cancer cells as measured by inhibition of pS6 and pAkt (S473).

High COVID-19 transmission potential associated with re-opening universities can be mitigated with layered interventions.

Controlling COVID-19 transmission in universities poses challenges due to the complex social networks and potential for asymptomatic spread. We developed a stochastic transmission model based on realistic mixing patterns and evaluated alternative mitigation strategies. We predict, for plausible model parameters, that if asymptomatic cases are half as infectious as symptomatic cases, then 15% (98% Prediction Interval: 6-35%) of students could be infected during the first term without additional control measures. First year students are the main drivers of transmission with the highest infection rates, largely due to communal residences. In isolation, reducing face-to-face teaching is the most effective intervention considered, however layering multiple interventions could reduce infection rates by 75%. Fortnightly or more frequent mass testing is required to impact transmission and was not the most effective option considered. Our findings suggest that additional outbreak control measures should be considered for university settings.

Psychosocial Interventions to Improve Psychological, Social and Physical Wellbeing in Family Members Affected by an Adult Relative's Substance Use: A Systematic Search and Review of the Evidence.

It is estimated that over 100 million people worldwide are affected by the substance use of a close relative and often experience related adverse health and social outcomes. There is a growing body of literature evaluating psychosocial interventions intended to reduce these adverse outcomes. We searched the international literature, using rigorous systematic methods to search and review the evidence for effective interventions to improve the wellbeing of family members affected by the substance use of an adult relative. We synthesised the evidence narratively by intervention type, in line with the systematic search and review approach. Sixty-five papers (from 58 unique trials) meeting our inclusion criteria were identified. Behavioural interventions delivered conjointly with the substance user and the affected family members were found to be effective in improving the social wellbeing of family members (reducing intimate partner violence, enhancing relationship satisfaction and stability and family functioning). Affected adult family members may derive psychological benefit from an adjacent individually focused therapeutic intervention component. No interventions fully addressed the complex multidimensional adversities experienced by many families affected by substance use. Further research is needed to determine the effect of a multi-component psychosocial intervention, which seeks to support both the substance user and the affected family member.