Impact of selective licensing schemes for private rental housing on mental health and social outcomes in Greater London, England: a natural experiment study.

OBJECTIVES: To assess primary impact of selective Licensing (SL), an area-based intervention in the private rented housing market, on individual self-reported anxiety and neighbourhood mental health (MHI-Mental Healthcare Index) and secondary impacts on antisocial behaviour (ASB), population turnover and self-reported well-being. DESIGN: Difference-in-difference (DiD) was used to evaluate effects of SL schemes initiated 2012-2018. 921 intervention areas (lower super output areas) were matched 3:1 using propensity scores derived from sociodemographic and housing variables (N=3.684 including controls). Average treatment effect on treated (ATT) was calculated for multiple time period DiD in area-level analyses. Canonical DiD was used for individual-level analysis by year of treatment initiation while adjusting for age, sex, native birth and occupational class. SETTING: Intervention neighbourhoods and control areas in Greater London, UK, 2011-2019. PARTICIPANTS: We sampled 4474 respondents renting privately in intervention areas (N=17 347 including controls) in Annual Population Survey and obtained area-level MHI population data. INTERVENTIONS: Private landlords in SL areas must obtain a licence from the local authority, allow inspection and maintain minimum housing standards. RESULTS: ATT after 5 years was significantly lower for MHI (-7.5%, 95% CI -5.6% to -8.8%) than controls. Antidepressant treatment days per population reduced by -5.4% (95% CI -3.7% to -7.3), mental health benefit receipt by -9.6% (95% CI -14% to -5.5%) and proportion with depression by -12% (95% CI -7.7% to -16.3%). ASB reduced by -15% (95% CI -21% to -8.2%). Population turnover increased by 26.5% (95% CI 22.1% to 30.8%). Sensitivity analysis suggests overlap with effects of London 2012 Olympic regeneration. No clear patterns were observed for self-reported anxiety. CONCLUSIONS: We found associations between SL and reductions in area-based mental healthcare outcomes and ASB, while population turnover increased. A national evaluation of SL is feasible and necessary.

Addressing alcohol-related harms in the local night-time economy: a qualitative process evaluation from a complex systems perspective.

OBJECTIVES: English local authorities (LAs) are interested in reducing alcohol-related harms and may use discretionary powers such as the Late Night Levy (LNL) to do so. This study aims to describe how system stakeholders hypothesise the levy may generate changes and to explore how the system, its actors and the intervention adapt and co-evolve over time. DESIGN: A process evaluation from a complex systems perspective, using qualitative methods. SETTING: A London LA with high densities of residential and commercial properties, which implemented the LNL in 2014. PARTICIPANTS: Data were generated through interviews with LNL implementers and alcohol consumers, observations in bars and during LNL patrols and documentary review. INTERVENTION: The LNL allows LAs to charge late-night alcohol retailers an annual fee (£299-£4440) to manage and police the night-time economy (NTE). RESULTS: When the LNL was being considered, stakeholders from different interest groups advanced diverse opinions about its likely impacts while rarely referencing supporting research evidence. Proponents of the levy argued it could reduce crime and anti-social behaviour by providing additional funds to police and manage the NTE. Critics of the levy hypothesised adverse consequences linked to claims that the intervention would force venues to vary their hours or close, cluster closing times, reduce NTE diversity and undermine public-private partnerships. In the first 2 years, levy-funded patrols developed relationships with the licensed trade and the public. The LNL did not undermine public-private partnerships and while some premises varied their hours, these changes did not undermine the intervention's viability, nor significantly cluster venue closing times, nor obviously damage the area's reputation for having a diverse NTE. CONCLUSIONS: This study applies a framework for process evaluation from a complex systems perspective. The evaluation could be extended to measure alcohol-related outcomes and to consider the interplay between the national and local systems.

Unselected Population Genetic Testing for Personalised Ovarian Cancer Risk Prediction: A Qualitative Study Using Semi-Structured Interviews.

Unselected population-based personalised ovarian cancer (OC) risk assessments combining genetic, epidemiological and hormonal data have not previously been undertaken. We aimed to understand the attitudes, experiences and impact on the emotional well-being of women from the general population who underwent unselected population genetic testing (PGT) for personalised OC risk prediction and who received low-risk (<5% lifetime risk) results. This qualitative study was set within recruitment to a pilot PGT study using an OC risk tool and telephone helpline. OC-unaffected women ≥ 18 years and with no prior OC gene testing were ascertained through primary care in London. In-depth, semi-structured and 1:1 interviews were conducted until informational saturation was reached following nine interviews. Six interconnected themes emerged: health beliefs; decision making; factors influencing acceptability; effect on well-being; results communication; satisfaction. Satisfaction with testing was high and none expressed regret. All felt the telephone helpline was helpful and should remain optional. Delivery of low-risk results reduced anxiety. However, care must be taken to emphasise that low risk does not equal no risk. The main facilitators were ease of testing, learning about children's risk and a desire to prevent disease. Barriers included change in family dynamics, insurance, stigmatisation and personality traits associated with stress/worry. PGT for personalised OC risk prediction in women in the general population had high acceptability/satisfaction and reduced anxiety in low-risk individuals. Facilitators/barriers observed were similar to those reported with genetic testing from high-risk cancer clinics and unselected PGT in the Jewish population.

Assessing the impact of selective licencing schemes for private rental housing on mental health and well-being: protocol for a mixed-method natural experiment study in Greater London, UK.

INTRODUCTION: The UK private rental housing market has poorer quality housing compared with other sectors and is subjected to calls for better regulation. Poor quality housing poses risks to mental and physical health, and housing improvement can potentially benefit health and well-being. Local authorities have powers to implement selective licencing (SL) schemes in specific localities. Such schemes involve landlord registration, payment of licence fees, local authority inspection and requirements that landlords conduct any necessary renovation works to ensure housing standards are met. We aim to evaluate SL in Greater London and to test the feasibility of a national evaluation. METHODS AND ANALYSIS: We will measure individual-level and area-level impacts of SL in Greater London between 2011 and 2019. A difference-in-differences approach with propensity score-matched controls will be used. We propose to exploit data from the Annual Population Survey (APS) and health and social benefit registers to measure mental health and well-being at individual (self-reported anxiety) and area (Small Area Mental Health Index) level. We estimate 633 APS participants in our intervention groups compared with 1899 participants in control areas (1:3 ratio of intervention to control). Secondary outcomes will be self-reported well-being and residential stability at the individual level and incidence of police-recorded antisocial behaviour calls and population turnover at the area level. The study size of the area-level analyses will be 3684 lower layer super output areas (including controls). Qualitative semistructured interviews with lead implementers in several London boroughs will produce insights into variations and commonalities between schemes. ETHICS AND DISSEMINATION: Ethical approval was obtained from London School of Hygiene and Tropical Medicine's Ethics Committee (reference number 26481) and London Borough of Hackney. All interviewees will be asked for informed written consent. Study findings will be published in a peer-reviewed journal.

Surgical decision making in premenopausal BRCA carriers considering risk-reducing early salpingectomy or salpingo-oophorectomy: a qualitative study.

BACKGROUND: Acceptance of the role of the fallopian tube in 'ovarian' carcinogenesis and the detrimental sequelae of surgical menopause in premenopausal women following risk-reducing salpingo-oophorectomy (RRSO) has resulted in risk-reducing early-salpingectomy with delayed oophorectomy (RRESDO) being proposed as an attractive alternative risk-reducing strategy in women who decline/delay oophorectomy. We present the results of a qualitative study evaluating the decision-making process among BRCA carriers considering prophylactic surgeries (RRSO/RRESDO) as part of the multicentre PROTECTOR trial (ISRCTN:25173360). METHODS: In-depth semistructured 1:1 interviews conducted using a predeveloped topic-guide (development informed by literature review and expert consultation) until informational saturation reached. Wording and sequencing of questions were left open with probes used to elicit additional information. All interviews were audio-recorded, transcribed verbatim, transcripts analysed using an inductive theoretical framework and data managed using NVIVO-v12. RESULTS: Informational saturation was reached following 24 interviews. Seven interconnected themes integral to surgical decision making were identified: fertility/menopause/cancer risk reduction/surgical choices/surgical complications/sequence of ovarian-and-breast prophylactic surgeries/support/satisfaction. Women for whom maximising ovarian cancer risk reduction was relatively more important than early menopause/quality-of-life preferred RRSO, whereas those more concerned about detrimental impact of menopause chose RRESDO. Women managed in specialist familial cancer clinic settings compared with non-specialist settings felt they received better quality care, improved hormone replacement therapy access and were more satisfied. CONCLUSION: Multiple contextual factors (medical, physical, psychological, social) influence timing of risk-reducing surgeries. RRESDO offers women delaying/declining premenopausal oophorectomy, particularly those concerned about menopausal effects, a degree of ovarian cancer risk reduction while avoiding early menopause. Care of high-risk women should be centralised to centres with specialist familial gynaecological cancer risk management services to provide a better-quality, streamlined, holistic multidisciplinary approach.

Evaluation of public health interventions from a complex systems perspective: A research methods review.

INTRODUCTION: Applying a complex systems perspective to public health evaluation may increase the relevance and strength of evidence to improve health and reduce health inequalities. In this review of methods, we aimed to: (i) classify and describe different complex systems methods in evaluation applied to public health; and (ii) examine the kinds of evaluative evidence generated by these different methods. METHODS: We adapted critical review methods to identify evaluations of public health interventions that used systems methods. We conducted expert consultation, searched electronic databases (Scopus, MEDLINE, Web of Science), and followed citations of relevant systematic reviews. Evaluations were included if they self-identified as using systems- or complexity-informed methods and if they evaluated existing or hypothetical public health interventions. Case studies were selected to illustrate different types of complex systems evaluation. FINDINGS: Seventy-four unique studies met our inclusion criteria. A framework was developed to map the included studies onto different stages of the evaluation process, which parallels the planning, delivery, assessment, and further delivery phases of the interventions they seek to inform; these stages include: 1) theorising; 2) prediction (simulation); 3) process evaluation; 4) impact evaluation; and 5) further prediction (simulation). Within this framework, we broadly categorised methodological approaches as mapping, modelling, network analysis and 'system framing' (the application of a complex systems perspective to a range of study designs). Studies frequently applied more than one type of systems method. CONCLUSIONS: A range of complex systems methods can be utilised, adapted, or combined to produce different types of evaluative evidence. Further methodological innovation in systems evaluation may generate stronger evidence to improve health and reduce health inequalities in our complex world.

Applying a complex systems perspective to alcohol consumption and the prevention of alcohol-related harms in the 21st century: a scoping review.

BACKGROUND AND AIMS: A complex systems perspective has been advocated to explore multi-faceted factors influencing public health issues, including alcohol consumption and associated harms. This scoping review aimed to identify studies that applied a complex systems perspective to alcohol consumption and the prevention of alcohol-related harms in order to summarize their characteristics and identify evidence gaps. METHODS: Studies published between January 2000 and September 2020 in English were located by searching for terms synonymous with 'complex systems' and 'alcohol' in the Scopus, MEDLINE, Web of Science and Embase databases, and through handsearching and reference screening of included studies. Data were extracted on each study's aim, country, population, alcohol topic, system levels, funding, theory, methods, data sources, time-frames, system modifications and type of findings produced. RESULTS: Eighty-seven individual studies and three systematic reviews were identified, the majority of which were conducted in the United States or Australia in the general population, university students or adolescents. Studies explored types and patterns of consumption behaviour and the local environments in which alcohol is consumed. Most studies focused on individual and local interactions and influences, with fewer examples exploring the relationships between these and regional, national and international subsystems. The body of literature is methodologically diverse and includes theory-led approaches, dynamic simulation models and social network analyses. The systematic reviews focused on primary network studies. CONCLUSIONS: The use of a complex systems perspective has provided a variety of ways of conceptualizing and analyzing alcohol use and harm prevention efforts, but its focus ultimately has remained on predominantly individual- and/or local-level systems. A complex systems perspective represents an opportunity to address this gap by also considering the vertical dimensions that constrain, shape and influence alcohol consumption and related harms, but the literature to date has not fully captured this potential.

Qualitative process evaluation from a complex systems perspective: A systematic review and framework for public health evaluators.

BACKGROUND: Public health evaluation methods have been criticized for being overly reductionist and failing to generate suitable evidence for public health decision-making. A "complex systems approach" has been advocated to account for real world complexity. Qualitative methods may be well suited to understanding change in complex social environments, but guidance on applying a complex systems approach to inform qualitative research remains limited and underdeveloped. This systematic review aims to analyze published examples of process evaluations that utilize qualitative methods that involve a complex systems perspective and proposes a framework for qualitative complex system process evaluations. METHODS AND FINDINGS: We conducted a systematic search to identify complex system process evaluations that involve qualitative methods by searching electronic databases from January 1, 2014-September 30, 2019 (Scopus, MEDLINE, Web of Science), citation searching, and expert consultations. Process evaluations were included if they self-identified as taking a systems- or complexity-oriented approach, integrated qualitative methods, reported empirical findings, and evaluated public health interventions. Two reviewers independently assessed each study to identify concepts associated with the systems thinking and complexity science traditions. Twenty-one unique studies were identified evaluating a wide range of public health interventions in, for example, urban planning, sexual health, violence prevention, substance use, and community transformation. Evaluations were conducted in settings such as schools, workplaces, and neighborhoods in 13 different countries (9 high-income and 4 middle-income). All reported some utilization of complex systems concepts in the analysis of qualitative data. In 14 evaluations, the consideration of complex systems influenced intervention design, evaluation planning, or fieldwork. The identified studies used systems concepts to depict and describe a system at one point in time. Only 4 evaluations explicitly utilized a range of complexity concepts to assess changes within the system resulting from, or co-occurring with, intervention implementation over time. Limitations to our approach are including only English-language papers, reliance on study authors reporting their utilization of complex systems concepts, and subjective judgment from the reviewers relating to which concepts featured in each study. CONCLUSION: This study found no consensus on what bringing a complex systems perspective to public health process evaluations with qualitative methods looks like in practice and that many studies of this nature describe static systems at a single time point. We suggest future studies use a 2-phase framework for qualitative process evaluations that seek to assess changes over time from a complex systems perspective. The first phase involves producing a description of the system and identifying hypotheses about how the system may change in response to the intervention. The second phase involves following the pathway of emergent findings in an adaptive evaluation approach.

Yes, not now, or never: an analysis of reasons for refusing or accepting emergency department-based take-home naloxone.

OBJECTIVE: Take-home naloxone (THN) reduces deaths from opioid overdose. To increase THN distribution to at-risk emergency department (ED) patients, we explored reasons for patients' refusing or accepting THN. METHODS: In an urban teaching hospital ED, we identified high opioid overdose risk patients according to pre-specified criteria. We offered eligible patients THN and participation in researcher-administered surveys, which inquired about reasons to refuse or accept THN and about THN dispensing location preferences. We analyzed refusal and acceptance reasons in open-ended responses, grouped reasons into categories (absolute versus conditional refusals,) then searched for associations between patient characteristics and reasons. RESULTS: Of 247 patients offered THN, 193 (78.1%) provided reasons for their decision. Of those included, 69 (35.2%) were female, 91 (47.2%) were under age 40, 61 (31.6%) were homeless, 144 (74.6%) reported injection drug use (IDU), and 131 (67.9%) accepted THN. Of 62 patients refusing THN, 19 (30.7%) felt "not at risk" for overdose, while 28 (45.2%) gave conditional refusal reasons: "too sick," "in a rush," or preference to get THN elsewhere. Non-IDU was associated with stating "not at risk," while IDU, homelessness, and age under 40 were associated with conditional refusals. Among acceptances, 86 (65.7%) mentioned saving others as a reason. Most respondents preferred other dispensing locations beside the ED, whether or not they accepted ED THN. CONCLUSION: ED patients refusing THN felt "not at risk" for overdose or felt their ED visit was not the right time or place for THN. Most accepting THN wanted to save others.

Universal screening at age 1-2 years as an adjunct to cascade testing for familial hypercholesterolaemia in the UK: A cost-utility analysis.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is widely underdiagnosed. Cascade testing (CT) of relatives has been shown to be feasible, acceptable and cost-effective in the UK, but requires a supply of index cases. Feasibility of universal screening (US) at age 1-2 years was recently demonstrated. We examined whether this would be a cost-effective adjunct to CT in the UK, given the current and plausible future undiagnosed FH prevalence. METHODS: Seven cholesterol and/or mutation-based US ±â€¯reverse cascade testing (RCT) alternatives were compared with no US in an incremental analysis with a healthcare perspective. A decision model was used to estimate costs and outcomes for cohorts exposed to the US component of each strategy. RCT case ascertainment was modelled using recent UK CT data, and probabilistic Markov models estimated lifetime costs and health outcomes for the cohorts screened under each alternative. 1000 Monte Carlo simulations were run for each model, and average outcomes reported. Further uncertainty was explored deterministically. Threshold analysis investigated the association between undiagnosed FH prevalence and cost-effectiveness. RESULTS: A strategy involving cholesterol screening followed by diagnostic genetic testing and RCT was the most cost-effective modelled (incremental cost-effectiveness ratio (ICER) versus no US £12,480/quality adjusted life year (QALY); probability of cost-effectiveness 96·8% at £20,000/QALY threshold). Cost-effectiveness was robust to both deterministic sensitivity analyses and threshold analyses that modelled ongoing case ascertainment at theoretical maximum levels. CONCLUSIONS: These findings support implementation of universal cholesterol screening followed by diagnostic genetic testing and RCT for FH, under a UK conventional willingness-to-pay threshold.

A Mixed-Methods Evaluation of a Community-Based Glaucoma Check Service in Hackney, London, UK.

PURPOSE: To evaluate the uptake, feasibility and acceptability of a general practice-based optometrist-led glaucoma check service. The service targeted people of black Caribbean and black African descent aged 40-65 years, resident in Hackney, London, United Kingdom. METHODS: The study used a mixed-method design, including analysis of service data, prospective audit of secondary care referrals patient survey, cost-consequence analysis, and interviews with staff involved in developing and implementing the service. RESULTS: A total of 3040 patients were invited to undergo the free check; 595 (19.6%) booked an appointment and 461 (15.2%) attended. Overall, 31 patients (6.8%) were referred to secondary care, of whom 22 attended and were assessed for glaucoma. Four were diagnosed with glaucoma and eight with suspected glaucoma, i.e. 2.6% of patients who underwent the check. The cost per patient identified with suspected or confirmed glaucoma was £9,013. Staff who were interviewed suggested that patients who attended might be those who routinely attended optometrist appointments, however only 62.4% of survey respondents reported having had an eye examination in the previous two years, and 11.4% of women and 16.0% of men reported never having had an eye examination. CONCLUSION: This study represents one possible configuration for a glaucoma case-finding service, and it contributes to a wider debate about whether screening, targeted or otherwise, should be offered in the UK. Our findings suggest that general practice is an acceptable setting and that such a service may reach some people not previously engaged with primary eye care services.

Factors Associated With Participation in an Emergency Department-Based Take-Home Naloxone Program for At-Risk Opioid Users.

STUDY OBJECTIVE: Although the World Health Organization recommends take-home naloxone to address the increasing global burden of opioid-related deaths, few emergency departments (EDs) offer a take-home naloxone program. We seek to determine the take-home naloxone acceptance rate among ED patients at high risk of opioid overdose and to examine factors associated with acceptance. METHODS: At a single urban ED, consecutive eligible patients at risk of opioid overdose were invited to complete a survey about opioid use, overdose experience, and take-home naloxone awareness, and then offered take-home naloxone. The primary outcome was acceptance of take-home naloxone, including the kit and standardized patient training. Univariate and multivariable logistic analyses were used to evaluate factors associated with acceptance. RESULTS: Of 241 eligible patients approached, 201 (83.4%) completed the questionnaire. Three-quarters of respondents used injection drugs, 37% were women, and 26% identified as "Indigenous." Of 201 respondents, 137 (68.2%; 95% confidence interval [CI] 61.7% to 74.7%) accepted take-home naloxone. Multivariable analysis revealed that factors associated with take-home naloxone acceptance included witnessing overdose in others (odds ratio [OR] 4.77; 95% CI 2.25 to 10.09), concern about own overdose death (OR 3.71; 95% CI 1.34 to 10.23), female sex (OR 2.50; 95% CI 1.21 to 5.17), and injection drug use (OR 2.22; 95% CI 1.06 to 4.67). CONCLUSION: A two-thirds ED take-home naloxone acceptance rate in patients using opioids should encourage all EDs to dispense take-home naloxone. ED-based take-home naloxone programs have the potential to improve access to take-home naloxone and awareness in individuals most vulnerable to overdoses.

Consequences of removing cheap, super-strength beer and cider: a qualitative study of a UK local alcohol availability intervention.

OBJECTIVES: Increasingly, English local authorities have encouraged the implementation of an intervention called 'Reducing the Strength' (RtS) whereby off-licences voluntarily stop selling inexpensive 'super-strength' (≥6.5% alcohol by volume (ABV)) beers and ciders. We conceptualised RtS as an event within a complex system in order to identify pathways by which the intervention may lead to intended and unintended consequences. DESIGN: A qualitative study including a focus group and semistructured interviews. SETTING: An inner-London local authority characterised by a high degree of residential mobility, high levels of social inequality and a large homeless population. Intervention piloted in three areas known for street drinking with a high alcohol outlet density. PARTICIPANTS: Alcohol service professionals, homeless hostel employees, street-based services managers and hostel dwelling homeless alcohol consumers (n=30). RESULTS: Participants describe a range of potential substitution behaviours to circumvent alcohol availability restrictions including consuming different drinks, finding alternative shops, using drugs or committing crimes to purchase more expensive drinks. Service providers suggested the intervention delivered in this local authority missed opportunities to encourage engagement between the council, alcohol services, homeless hostels and off-licence stores. Some participants believed small-scale interventions such as RtS may facilitate new forms of engagement between public and private sector interests and contribute to long-term cultural changes around drinking, although they may also entrench the view that 'problem drinking' only occurs in certain population groups. CONCLUSIONS: RtS may have limited individual-level health impacts if the target populations remain willing and able to consume alternative means of intoxication as a substitute for super-strength products. However, RtS may also lead to wider system changes not directly related to the consumption of super-strengths and their assumed harms.

The views of genitourinary medicine (GUM) clinic users on unlinked anonymous testing for HIV: evidence from a pilot study of clinics in two English cities.

A study was undertaken of the views of users of two genitourinary medicine (GUM) clinics in England on unlinked anonymous testing (UAT) for HIV. The UAT programme measures the prevalence of HIV in the population, including undiagnosed prevalence, by testing residual blood (from samples taken for clinical purposes) which is anonymised and irreversibly unlinked from the source. 424 clinic users completed an anonymous questionnaire about their knowledge of, and attitudes towards, UAT. Only 1/7 (14%) were aware that blood left over from clinical testing may be tested anonymously for HIV. A large majority (89%) said they would agree to their blood being tested, although 74% wanted the opportunity to consent. These findings indicate broad support for UAT of blood in a group of patients whose samples are included in the HIV surveillance programme. The findings suggest the need for greater attention to be given to the provision of information and, if replicated in a larger survey, may justify a reappraisal of UK policy on UAT.

Cost-effectiveness analysis of the genetic screening program for familial hypercholesterolemia in The Netherlands.

Familial hypercholesterolemia (FH) is associated with pronounced atherosclerosis leading to premature cardiovascular disease and untimely death. Despite the availability of effective preventative drug treatments, many affected individuals remain undiagnosed and untreated until they become symptomatic with cardiovascular disease. To assess the cost-effectiveness of systematic genetic screening of family members of persons diagnosed with FH, an analysis was conducted using data from a nationwide screening program for the identification of individuals with FH, instituted in The Netherlands in 1994, and from other sources. There was DNA testing of families with a known genetic defect to identify new cases of FH in the presymptomatic stage of the disease. After identification, most newly identified patients were started on cholesterol-lowering statin treatment. On average, new cases diagnosed by the screening program gained 3.3 years of life each. Twenty-six myocardial infarctions would be avoided for every 100 persons treated with statins between the ages of 18 and 60 years. The average total lifetime incremental costs, over all age ranges and both sexes, including costs for screening and testing, lifetime drug treatment, and treatment of cardiovascular events, was US dollars 7500 per new case identified. Cost per life-year gained was US dollars 8700. Therefore, systematic genetic screening of family members of persons diagnosed with FH is cost-effective in The Netherlands and should be considered for other settings.

A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia.

BACKGROUND: Familial hypercholesterolaemia (FH) affects approximately 1 in 500 people (10 million world-wide) and the elevated serum cholesterol concentrations lead to a more than 50% risk of fatal or non-fatal coronary heart disease by age 50 years in men and at least 30% in women aged 60 years. Based on a systematic literature search, we review the natural history of FH, describe the diagnostic criteria, and consider the effectiveness of treatment. METHODS: A comprehensive review was conducted of the literature on the diagnosis of FH, the morbidity and mortality related to treated and untreated FH, and the evidence on the effectiveness of treatment of FH in adults and children. Treatment options have changed since statin treatment became available, and we have not considered pre-statin therapy studies of treatment effectiveness. FINDINGS AND DISCUSSION: A clinical diagnosis of FH is widely used, but a definitive diagnosis can be made by genetic screening, although mutations are currently only detected in 30-50% of patients with a clinical diagnosis. Under-diagnosis of FH has been reported world-wide ranging from less than 1% to 44%. The relative risk of death of FH patients not treated with statins is between three and fourfold but treatment is effective, and delays or prevents the onset of coronary heart disease. Early detection and treatment is important. Aggressive LDL therapy is more effective in the regression of the carotid intima media thickness than conventional LDL therapy. Diagnosis at birth is problematic, and should be delayed until at least 2 years of age. Statins are not generally recommended for the treatment of children up to adolescence. Resins may be used but poor adherence is a problem. Technical advances in mutation detection, and the identification of other genes that cause FH, are likely to have important implications for the cost effectiveness of genetic diagnosis of FH.

Comparing costs and benefits over a 10 year period of strategies for familial hypercholesterolaemia screening.

BACKGROUND: Approximately 110,000 people in the United Kingdom are affected with familial hypercholesterolaemia (FH). At least 75 per cent are undiagnosed. Treatment with statins is effective but effective primary prevention requires early diagnosis. The best strategy to achieve this is unclear. This paper compares the costs and benefits over a 10 year period of two strategies found in our previous modelling: population screening of 16-year-olds or tracing family members of affected patients. METHODS: Computer modelling of time-limited data was conducted. The number available for screening and the potential new cases in England and Wales aged 16-54 years were estimated. The costs (of screening and treatment) and benefits (deaths averted) that might be accrued over 10 years were assessed. RESULTS: Screening 16-year-olds results in 470 new diagnoses, and over 10 subsequent years averts 11.7 deaths at a cost of 6,176,648 pounds sterling, giving a cost per case identified and treated of 13,141 pounds sterling (including a 10 year drug cost of 1,584,918 pounds sterling). By contrast, screening first-degree relatives of known uases results in 13,248 new diagnoses, 560 deaths averted over 10 years, at a cost of 46,430,681 pounds sterling giving a cost per case identified and treated of 3,505 pounds sterling (including 10 year drug cost of 44,645,760 pounds sterling). The cost per death averted would be 3,187 pounds sterling. CONCLUSIONS: Although the two approaches appear similar in cost-effectiveness over a lifetime, the shorter-term (10 year) cost-effectiveness clearly favours family tracing. This represents good value for money compared with common medical interventions, and suggests that pilot FH family tracing programmes should be conducted.

Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia.

OBJECTIVES: To assess the cost effectiveness of strategies to screen for and treat familial hypercholesterolaemia. DESIGN: Cost effectiveness analysis. A care pathway for each patient was delineated and the associated probabilities, benefits, and costs were calculated. PARTICIPANTS: Simulated population aged 16-54 years in England and Wales. INTERVENTIONS: Identification and treatment of patients with familial hypercholesterolaemia by universal screening, opportunistic screening in primary care, screening of people admitted to hospital with premature myocardial infarction, or tracing family members of affected patients. MAIN OUTCOME MEASURE: Cost effectiveness calculated as cost per life year gained (extension of life expectancy resulting from intervention) including estimated costs of screening and treatment. RESULTS: Tracing of family members was the most cost effective strategy (3097 pounds sterling (euros 5066, $4479) per life year gained) as 2.6 individuals need to be screened to identify one case at a cost of 133 pounds sterling per case detected. If the genetic mutation was known within the family then the cost per life year gained (4914 pounds sterling ) was only slightly increased by genetic confirmation of the diagnosis. Universal population screening was least cost effective (13 029 pounds sterling per life year gained) as 1365 individuals need to be screened at a cost of 9754 pounds sterling per case detected. For each strategy it was more cost effective to screen younger people and women. Targeted strategies were more expensive per person screened, but the cost per case detected was lower. Population screening of 16 year olds only was as cost effective as family tracing (2777 pounds sterling with a clinical confirmation). CONCLUSIONS: Screening family members of people with familial hypercholesterolaemia is the most cost effective option for detecting cases across the whole population.