Whole-school interventions promoting student commitment to school to prevent substance use and violence, and improve educational attainment: a systematic review.

Background: Whole-school interventions modify the school environment to promote health. A subset of these interventions promotes student commitment to school to prevent substance (tobacco, alcohol, other drugs) use and/or violence. A previous review identified the theory of human functioning and school organisation as a comprehensive theory of such interventions, and found evidence that these interventions reduce substance use and/or violence. Objectives: The objectives were to search for, appraise and synthesise evidence to address the following questions: (1) What whole-school interventions promoting student commitment to school to prevent substance use and/or violence have been evaluated, what intervention subtypes are apparent and how closely do these align with the theory of human functioning and school organisation? (2) What factors relating to setting, population and intervention affect implementation? (3) What are the effects on student substance use, violence and educational attainment? (4) What is the cost-effectiveness of such interventions? (5) Are intervention effects mediated by student commitment to school or moderated by setting or population? Data sources: A total of 56 information sources were searched (in January 2020), then an updated search of 48 of these was carried out (in May 2021). Reference lists were also searched and experts were contacted. Review methods: Eligible studies were process/outcome evaluations of whole-school interventions to reduce student violence or substance use among students aged 5-18 years attending schools, via actions aligning with the theory of human functioning and school organisation: modifying teaching to increase engagement, enhancing student-staff relationships, revising school policies, encouraging volunteering or increasing parental involvement. Data extraction and quality assessments used existing tools. Theory and process reports were synthesised qualitatively. Outcome and economic data were synthesised narratively; outcome data were meta-analysed. Results: Searches retrieved 63 eligible reports on 27 studies of 22 interventions. We identified four intervention subtypes focused on student participation in school-wide decisions, improving staff-student relationships, increasing engagement in learning and involving parents. The theories of change of most intervention subtypes aligned closely with the theory of human functioning and school organisation, and informed refinement of an intervention theory of change. Theories of change for interventions increasing learning engagement did not align with this theory, aiming instead to increase school commitment primarily via social skills curricula. Factors influencing the implementation included whether or not interventions were tailorable, workable and well explained. Interventions with action groups comprising staff/students, etc. and providing local data were well implemented. Implementation was also affected by whether or not schools accepted the need for change and staff had the resources for delivery. Meta-analyses suggest small, but significant, intervention effects in preventing violence victimisation and perpetration, and substance use. There was sparse and inconsistent evidence of moderation and some evidence of mediation by student commitment to school. Two economic evaluations suggested that there is the potential for the interventions to be cost-effective. Limitations: The quality of the studies was variable and the economic synthesis was limited to two studies. Conclusions: Whole-school interventions aiming to promote student commitment to school share similar theories of change and factors affecting implementation. They have the potential to contribute to preventing violence and substance use among young people. Future trials should aim to optimise intervention effectiveness by better theorisation, and assess implementation and effect moderators and mediators. Study registration: This study is registered as PROSPERO CRD42019154334. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 17/151/05) and is published in full in Public Health Research; Vol. 12, No. 2. See the NIHR Funding and Awards website for further award information.

Whole-school health interventions aim to modify how schools are run, to promote students' health. Some aim to promote student commitment to school to prevent the important interlinked outcomes of substance (tobacco, alcohol, other drugs) use and violence. We searched for all evaluations of such interventions. We summarised what this research said about the sorts of interventions used, how they are meant to work, what factors affect delivery, whether or not they reduce violence and substance use and whether or not they are worth the money. We found 63 reports on 27 studies of 22 interventions. We identified four subtypes of interventions. These aimed to involve students in school decisions, improve staff­student relationships, increase engagement in learning or involve parents. Most of these interventions were intended to work by making sure schools focused on student needs, or by improving relationships between staff and students, between different areas of learning or between schools and communities. This aimed to make students feel committed to school and therefore avoid violence or substance use. A few aimed to work mostly by teaching students how to avoid violence and substance use. We found that interventions were well implemented if they were tailored for each school and had good materials and support. Interventions were well delivered if they were led by action groups (comprising staff, students, etc.) or provided schools with information on students' needs. Implementation was affected by whether or not schools accepted the need for change and whether or not staff had the necessary time and money to do the work. These interventions appear to have small, but significant, intervention impacts in preventing violence and substance use among young people. There was not consistent evidence of different effects for different students. A small number of studies suggest that such interventions might show economic benefit, but this would need further research. Future research should focus on interventions that are refined to make sure that they can be well delivered.

Observation versus screening spinal MRI and pre-emptive treatment for spinal cord compression in patients with castration-resistant prostate cancer and spinal metastases in the UK (PROMPTS): an open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Early diagnosis of malignant spinal cord compression (SCC) is crucial because pretreatment neurological status is the major determinant of outcome. In metastatic castration-resistant prostate cancer, SCC is a clinically significant cause of disease-related morbidity and mortality. We investigated whether screening for SCC with spinal MRI, and pre-emptive treatment if radiological SCC (rSCC) was detected, reduced the incidence of clinical SCC (cSCC) in asymptomatic patients with metastatic castration-resistant prostate cancer and spinal metastasis. METHODS: We did a parallel-group, open-label, randomised, controlled, phase 3, superiority trial. Patients with metastatic castration-resistant prostate cancer were recruited from 45 National Health Service hospitals in the UK. Eligible patients were aged at least 18 years, with an Eastern Co-operative Oncology Group performance status of 0-2, asymptomatic spinal metastasis, no previous SCC, and no spinal MRI in the past 12 months. Participants were randomly assigned (1:1), using a minimisation algorithm with a random element (balancing factors were treatment centre, alkaline phosphatase [normal vs raised, with the upper limit of normal being defined at each participating laboratory], number of previous systemic treatments [first-line vs second-line or later], previous spinal treatment, and imaging of thorax and abdomen), to no MRI (control group) or screening spinal MRI (intervention group). Serious adverse events were monitored in the 24 h after screening MRI in the intervention group. Participants with screen-detected rSCC were offered pre-emptive treatment (radiotherapy or surgical decompression was recommended per treating physician's recommendation) and 6-monthly spinal MRI. All patients were followed up every 3 months, and then at month 30 and 36. The primary endpoint was time to and incidence of confirmed cSCC in the intention-to-treat population (defined as all patients randomly assigned), with the primary timepoint of interest being 1 year after randomisation. The study is registered with ISRCTN, ISRCTN74112318, and is now complete. FINDINGS: Between Feb 26, 2013, and April 25, 2017, 420 patients were randomly assigned to the control (n=210) or screening MRI (n=210) groups. Median age was 74 years (IQR 68 to 79), 222 (53%) of 420 patients had normal alkaline phosphatase, and median prostate-specific antigen concentration was 48 ng/mL (IQR 17 to 162). Screening MRI detected rSCC in 61 (31%) of 200 patients with assessable scans in the intervention group. As of data cutoff (April 23, 2020), at a median follow-up of 22 months (IQR 13 to 31), time to cSCC was not significantly improved with screening (hazard ratio 0·64 [95% CI 0·37 to 1·11]; Gray's test p=0·12). 1-year cSCC rates were 6·7% (95% CI 3·8-10·6; 14 of 210 patients) for the control group and 4·3% (2·1-7·7; nine of 210 patients) for the intervention group (difference -2·4% [95% CI -4·2 to 0·1]). Median time to cSCC was not reached in either group. No serious adverse events were reported within 24 h of screening. INTERPRETATION: Despite the substantial incidence of rSCC detected in the intervention group, the rate of cSCC in both groups was low at a median of 22 months of follow-up. Routine use of screening MRI and pre-emptive treatment to prevent cSCC is not warranted in patients with asymptomatic castration-resistant prostate cancer with spinal metastasis. FUNDING: Cancer Research UK.

A high-dose 24-hour tranexamic acid infusion for the treatment of significant gastrointestinal bleeding: HALT-IT RCT.

BACKGROUND: Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias. OBJECTIVE: The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding. DESIGN: A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat. SETTING: The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine. PARTICIPANTS: Adults with significant upper or lower gastrointestinal bleeding (n = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery. INTERVENTION: Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo. MAIN OUTCOME MEASURES: The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit. RESULTS: A total of 12,009 patients were allocated to receive tranexamic acid (n = 5994, 49.9%) or the matching placebo (n = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid. CONCLUSIONS: Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding. FUTURE WORK: These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes. LIMITATIONS: Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.

Acute gastrointestinal bleeding (bleeding from the gut) is a common emergency and an important cause of death and illness worldwide. In the UK, more than 65,000 people each year are admitted to hospital because of acute gastrointestinal bleeding; approximately 10% of them die within 30 days. Gastrointestinal bleeding is also common in low- and middle-income countries. The care of patients with gastrointestinal bleeding has improved in recent decades, but death rates remain high. Gastrointestinal bleeding is often caused by stomach ulcers, but also by liver damage owing to alcohol or hepatitis C infection. An effective and affordable treatment for gastrointestinal bleeding could save many lives and may reduce the need for blood transfusions, which is important because blood is a scarce resource in some health-care settings. Tranexamic acid, also known as TXA, is a cheap drug that reduces bleeding in other conditions. It helps blood to clot, thereby decreasing bleeding. A trial in bleeding accident victims found that tranexamic acid reduced the chances of bleeding to death, without any increase in side effects. We wanted to find out if tranexamic acid safely improves outcomes in patients with gastrointestinal bleeding, particularly to prevent deaths. To investigate this, the HALT-IT (Haemorrhage ALleviation with Tranexamic acid ­ Intestinal system) trial studied 12,009 patients with significant gastrointestinal bleeding in 164 hospitals across 15 countries. Half of the patients received tranexamic acid and the other half received a dummy drug, called a placebo. The treatments were assigned randomly and given in addition to all other treatments needed. Neither the patient nor the doctor knew which treatment a patient received. The trial showed that tranexamic acid did not reduce deaths from gastrointestinal bleeding. Instead, tranexamic acid was linked to an increased risk of complications, including unwanted blood clots (such as deep-vein thrombosis) and seizures. The economic analysis indicated that giving tranexamic acid to patients with gastrointestinal bleeding does not represent value for money for the NHS.

Causes of hospitalisation among a cohort of people with HIV from a London centre followed from 2011 to 2018.

BACKGROUND: We describe the spectrum of ICD-10 classified causes for hospitalisations occurring between 2011 and 2018 in a cohort of people living with HIV (PLHIV). METHODS: This sub-study includes 798 PLHIV participating in the Antiretroviral, Sexual Transmission Risk and Attitudes (ASTRA) questionnaire study who were recruited from a large London centre. A medical record review identified the occurrence and causes of hospitalisation from the date of questionnaire completion (February-December 2011) until 1 June 2018. Up to five causes were classified by an HIV clinician using the ICD-10 system. RESULTS: There were 274 hospitalisations in 153 people (rate = 5.8/100 person-years; 95% CI: 5.1, 6.5). Causes were wide-ranging; the most common were circulatory (16.8%), digestive (13.1%), respiratory (11.7%), infectious diseases (11.0%), injury/poisoning (10.6%), genitourinary diseases (9.9%) and neoplasms (9.1%). A tenth (27/274) of hospitalisations were related to at least one AIDS-defining illness. Median duration of hospitalisation was 5 days (IQR 2-9). At the time of hospitalisation, median CD4 count was high (510 cells/µl; IQR: 315-739), while median CD4 nadir was relatively low (113 cells/µl; IQR: 40-239). At admission, half of individuals (51%) had a previous AIDS-defining illness and 21% had viral load > 50 copies/ml. Individuals admitted for infectious diseases were particularly likely to have unfavourable HIV-related clinical characteristics (low CD4, viral non-suppression, not on antiretroviral therapy (ART), previous AIDS). CONCLUSIONS: In the modern combination antiretroviral therapy era, the spectrum of causes of hospitalisation in PLHIV in the UK is wide-ranging, highlighting the importance of holistic care for PLHIV, including prevention, early detection and treatment of comorbidities.

Costs and cost-effectiveness of cervical cancer screening strategies in women living with HIV in Burkina Faso: The HPV in Africa Research Partnership (HARP) study.

INTRODUCTION: This study estimated the costs and incremental cost per case detected of screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) attending HIV clinics in Burkina Faso. METHODS: The direct healthcare provider costs of screening tests (visual inspection with acetic acid (VIA), VIA combined visual inspection with Lugol's iodine (VIA/VILI), cytology and a rapid HPV DNA test (careHPV)) and confirmatory tests (colposcopy, directed biopsy and systematic four-quadrant (4Q) biopsy) were collected alongside the HPV in Africa Research Partnership (HARP) study. A model was developed for a hypothetical cohort of 1000 WLHIV using data on CIN2+ prevalence and the sensitivity of the screening tests. Costs are reported in USD (2019). RESULTS: The study enrolled 554 WLHIV with median age 36 years (inter-quartile range, 31-41) and CIN2+ prevalence of 5.8%. The average cost per screening test ranged from US$3.2 for VIA to US$24.8 for cytology. Compared to VIA alone, the incremental cost per CIN2+ case detected was US$48 for VIA/VILI and US$814 for careHPV. Despite higher costs, careHPV was more sensitive for CIN2+ cases detected compared to VIA/VILI (97% and 56%, respectively). The cost of colposcopy was US$6.6 per person while directed biopsy was US$33.0 and 4Q biopsy was US$48.0. CONCLUSION: Depending on the willingness to pay for the detection of a case of cervical cancer, decision makers in Burkina Faso can consider a variety of cervical cancer screening strategies for WLHIV. While careHPV is more costly, it has the potential to be cost-effective depending on the willingness to pay threshold. Future research should explore the lifetime costs and benefits of cervical cancer screening to enable comparisons with interventions for other diseases.

Prospective association of social circumstance, socioeconomic, lifestyle and mental health factors with subsequent hospitalisation over 6-7 year follow up in people living with HIV.

BACKGROUND: Predictors of hospitalisation in people with HIV (PLHIV) in the contemporary treatment era are not well understood. METHODS: This ASTRA sub-study used clinic data linkage and record review to determine occurrence of hospitalisations among 798 PLHIV from baseline questionnaire (February to December 2011) until 1 June 2018. Associations of baseline social circumstance, socioeconomic, lifestyle, mental health, demographic and clinical factors with repeated all-cause hospitalisation from longitudinal data were investigated using Prentice-Williams-Peterson models. Associations were also assessed in 461 individuals on antiretroviral therapy (ART) with viral load ≤50 copies/ml and CD4 count ≥500 cells/ µl. FINDINGS: Rate of hospitalisation was 5.8/100 person-years (95% CI: 5.1-6.5). Adjusted for age, demographic group and time with diagnosed HIV, the following social circumstance, socioeconomic, lifestyle and mental health factors predicted hospitalisation: no stable partner (adjusted hazard ratio (aHR)=1.59; 95% CI=1.16-2.20 vs living with partner); having children (aHR=1.50; 1.08-2.10); non-employment (aHR=1.56; 1.07-2.27 for unemployment; aHR=2.39; 1.70-3.37 for sick/disabled vs employed); rented housing (aHR=1.72; 1.26-2.37 vs homeowner); not enough money for basic needs (aHR=1.82; 1.19-2.78 vs enough); current smoking (aHR=1.39; 1.02-1.91 vs never); recent injection-drug use (aHR=2.11; 1.30-3.43); anxiety symptoms (aHRs=1.39; 1.01-1.91, 2.06; 1.43-2.95 for mild and moderate vs none/minimal); depressive symptoms (aHRs=1.67; 1.17-2.38, 1.91; 1.30-2.78 for moderate and severe vs none/minimal); treated/untreated depression (aHRs=1.65; 1.03-2.64 for treated depression only, 1.87; 1.39-2.52 for depressive symptoms only; 1.53; 1.05-2.24; for treated depression and depressive symptoms, versus neither). Associations were broadly similar in those with controlled HIV and high CD4. INTERPRETATION: Social circumstance, socioeconomic disadvantage, adverse lifestyle factors and poorer mental health are strong predictors of hospitalisation in PLHIV, highlighting the need for targeted interventions and care. FUNDING: British HIV Association (BHIVA) Research Award (2017); SMR funded by a PhD fellowship from the Royal Free Charity.

An Economic Evaluation of the Cost-Effectiveness of Opt-Out Hepatitis B and Hepatitis C Testing in an Emergency Department Setting in the United Kingdom.

OBJECTIVES: The prevalence of hepatitis is high in emergency department (ED) attendees in the United Kingdom, with a prevalence of up to 2% for hepatitis B (HBV) HBsAg, and 2.9% for hepatitis C (HCV) RNA. The aim of this paper is to perform an economic evaluation of opt-out ED-based HCV and HBV testing. METHODS: A Markov model was developed to analyze the cost-effectiveness of opt-out HCV and HBV testing in EDs in the UK. The model used data from UK studies of ED testing to parameterize the HCV and HBV prevalence (1.4% HCV RNA, 0.84% HBsAg), test costs, and intervention effects (contact rates and linkage to care). For HCV, we used an antibody test cost of £3.64 and RNA test cost of £68.38, and assumed direct-acting antiviral treatment costs of £10 000. For HBV, we used a combined HBsAg and confirmatory test cost of £5.79. We also modeled the minimum prevalence of HCV (RNA-positive) and HBV (HBsAg) required to make ED testing cost-effective at a £20 000 willingness to pay per quality-adjusted life-year threshold. RESULTS: In the base case, ED testing was highly cost-effective, with HCV and HBV testing costing £8019 and £9858 per quality-adjusted life-year gained, respectively. HCV and HBV ED testing remained cost-effective at 0.25% HCV RNA or HBsAg prevalence or higher. CONCLUSIONS: Emergency department testing for HCV and HBV is highly likely to be cost-effective in many areas across the UK depending on their prevalence. Ongoing studies will help evaluate ED testing across different regions to inform testing guidelines.

The clinical and cost-effectiveness of supplemental parenteral nutrition in oncology.

BACKGROUND: Clinical guidelines recommend that parenteral nutrition (PN) is added to enteral nutrition (EN; supplemental parenteral nutrition (SPN)) in order to meet energy and protein needs in patients with cancer when EN alone is insufficient. However, although cancer-related malnutrition is common, there is poor awareness of the value of nutritional care, resulting in SPN being chronically underused. METHODS: We performed a targeted literature review and exploratory cost-utility analysis to gather evidence on the clinical effectiveness of SPN, and to estimate the potential cost-effectiveness of SPN versus EN alone in an example cancer setting. RESULTS: The literature review identified studies linking SPN with malnutrition markers, and studies linking malnutrition markers with clinical outcomes. SPN was linked to improvements in body mass index (BMI), fat-free mass, phase angle (PhA) and prealbumin. Of these markers, BMI and PhA were strong predictors of survival. By combining published data, we generated indirect estimates of the overall survival HR associated with SPN; these ranged from 0.80 to 0.99 (mode 0.87). In patients with Stage IV inoperable pancreatic cancer, the incremental cost-effectiveness ratio versus EN alone was estimated to be £41 350 or £91 501 depending on whether nursing and home delivery costs for EN and SPN were combined or provided separately. CONCLUSION: Despite a lack of direct evidence, the results of the literature review demonstrate that SPN may provide important clinical and quality of life benefits to patients with cancer. The potential for any improvement in outcomes in the modelled patient population is very limited, so cost-effectiveness may be greater in patients with less severe disease and other types of cancer.

Cost-Effectiveness of One-Time Birth Cohort Screening for Hepatitis C as Part of the National Health Service Health Check Program in England.

BACKGROUND AND OBJECTIVES: Birth cohort screening for the hepatitis C virus (HCV) has been implemented in the US, but there is little evidence of its cost-effectiveness in England. We aim to evaluate the cost-effectiveness of one-time HCV screening for individuals born between 1950 and 1979 as part of the National Health Service health check in England, a health check for adults aged 40 to 74 years in primary care. METHODS: A Markov model was developed to analyze add-on HCV testing to the National Health Service health check for individuals in birth cohorts between 1950 and 1979, versus current background HCV testing only, over a lifetime horizon. The model used data from a back-calculation model of the burden of HCV in England, sentinel surveillance of HCV testing, and published literature. Results are presented from a health service perspective in pounds in 2017, as incremental cost-effectiveness ratios per quality-adjusted life years gained. RESULTS: The base-case incremental cost-effectiveness ratios ranged from £7648 to £24 434, and £18 681 to £46 024, across birth cohorts when considering 2 sources of HCV transition probabilities. The intervention is most likely to be cost-effective for those born in the 1970s, and potentially cost-effective for those born from 1955 to 1969. The model results were most sensitive to the source of HCV transition probabilities, the probability of referral and receiving treatment, and the HCV prevalence among testers. The maximum value of future research across all birth cohorts was £11.3 million at £20 000 per quality-adjusted life years gained. CONCLUSION: Birth cohort screening is likely to be cost-effective for younger birth cohorts, although considerable uncertainty exists for other birth cohorts. Further studies are warranted to reduce uncertainty in cost-effectiveness and consider the acceptability of the intervention.

A Cost-effectiveness Analysis of Multigene Testing for All Patients With Breast Cancer.

Importance: Moving to multigene testing for all women with breast cancer (BC) could identify many more mutation carriers who can benefit from precision prevention. However, the cost-effectiveness of this approach remains unaddressed. Objective: To estimate incremental lifetime effects, costs, and cost-effectiveness of multigene testing of all patients with BC compared with the current practice of genetic testing (BRCA) based on family history (FH) or clinical criteria. Design, Setting, and Participants: This cost-effectiveness microsimulation modeling study compared lifetime costs and effects of high-risk BRCA1/BRCA2/PALB2 (multigene) testing of all unselected patients with BC (strategy A) with BRCA1/BRCA2 testing based on FH or clinical criteria (strategy B) in United Kingdom (UK) and US populations. Data were obtained from 11 836 patients in population-based BC cohorts (regardless of FH) recruited to 4 large research studies. Data were collected and analyzed from January 1, 2018, through June 8, 2019. The time horizon is lifetime. Payer and societal perspectives are presented. Probabilistic and 1-way sensitivity analyses evaluate model uncertainty. Interventions: In strategy A, all women with BC underwent BRCA1/BRCA2/PALB2 testing. In strategy B, only women with BC fulfilling FH or clinical criteria underwent BRCA testing. Affected BRCA/PALB2 carriers could undertake contralateral preventive mastectomy; BRCA carriers could choose risk-reducing salpingo-oophorectomy (RRSO). Relatives of mutation carriers underwent cascade testing. Unaffected relative carriers could undergo magnetic resonance imaging or mammography screening, chemoprevention, or risk-reducing mastectomy for BC risk and RRSO for ovarian cancer (OC) risk. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained and compared with standard £30 000/QALY and $100 000/QALY UK and US thresholds, respectively. Incidence of OC, BC, excess deaths due to heart disease, and the overall population effects were estimated. Results: BRCA1/BRCA2/PALB2 multigene testing for all patients detected with BC annually would cost £10 464/QALY (payer perspective) or £7216/QALY (societal perspective) in the United Kingdom or $65 661/QALY (payer perspective) or $61 618/QALY (societal perspective) in the United States compared with current BRCA testing based on clinical criteria or FH. This is well below UK and US cost-effectiveness thresholds. In probabilistic sensitivity analysis, unselected multigene testing remained cost-effective for 98% to 99% of UK and 64% to 68% of US health system simulations. One year's unselected multigene testing could prevent 2101 cases of BC and OC and 633 deaths in the United Kingdom and 9733 cases of BC and OC and 2406 deaths in the United States. Correspondingly, 8 excess deaths due to heart disease occurred in the United Kingdom and 35 in the United States annually. Conclusions and Relevance: This study found unselected, high-risk multigene testing for all patients with BC to be extremely cost-effective compared with testing based on FH or clinical criteria for UK and US health systems. These findings support changing current policy to expand genetic testing to all women with BC.

Cost-utility of screening for depression among asylum seekers: a modelling study in Germany.

BACKGROUND: Asylum seekers have a high burden of mental illness owing to traumatic experiences before, during and after flight. Screening has been suggested to identify asylum seekers with psychosocial needs. However, little is known about the costs of screening relative to expected gains. We assessed the cost-utility of population-based screening for depression in German asylum reception centres compared to case-finding by self-referral. METHODS: Explorative modelling study using a decision tree over 15 months to estimate the incremental cost per quality-adjusted life-year gained. Data points were taken from the published literature. Deterministic and probabilistic sensitivity analyses were used to address uncertainty around parameter estimates. Value of information analyses were performed to indicate the value of future research. RESULTS: The model demonstrates a high probability (p = 83%) of the screening intervention being cost-effective at a Є 50,000/QALY threshold. Cost-utility depends on the process of care following screening: when acceptability and adherence parameters were decreased by 40%, the resulting ICER increased by 27-131%. Eliminating uncertainty was most valuable for the screening process and cost parameters, at Є 3·0 and Є 4·4 million respectively. CONCLUSIONS: Screening asylum seekers for depression may be a cost-effective strategy to identify those in need of care. However, there is considerable value in conducting further research in this area, especially regarding resource requirements and the process of care following screening.

Preferences for HIV testing services among men who have sex with men in the UK: A discrete choice experiment.

BACKGROUND: In the UK, approximately 4,200 men who have sex with men (MSM) are living with HIV but remain undiagnosed. Maximising the number of high-risk people testing for HIV is key to ensuring prompt treatment and preventing onward infection. This study assessed how different HIV test characteristics affect the choice of testing option, including remote testing (HIV self-testing or HIV self-sampling), in the UK, a country with universal access to healthcare. METHODS AND FINDINGS: Between 3 April and 11 May 2017, a cross-sectional online-questionnaire-based discrete choice experiment (DCE) was conducted in which respondents who expressed an interest in online material used by MSM were asked to imagine that they were at risk of HIV infection and to choose between different hypothetical HIV testing options, including the option not to test. A variety of different testing options with different defining characteristics were described so that the independent preference for each characteristic could be valued. The characteristics included where each test is taken, the sampling method, how the test is obtained, whether infections other than HIV are tested for, test accuracy, the cost of the test, the infection window period, and how long it takes to receive the test result. Participants were recruited and completed the instrument online, in order to include those not currently engaged with healthcare services. The main analysis was conducted using a latent class model (LCM), with results displayed as odds ratios (ORs) and probabilities. The ORs indicate the strength of preference for one characteristic relative to another (base) characteristic. In total, 620 respondents answered the DCE questions. Most respondents reported that they were white (93%) and were either gay or bisexual (99%). The LCM showed that there were 2 classes within the respondent sample that appeared to have different preferences for the testing options. The first group, which was likely to contain 86% of respondents, had a strong preference for face-to-face tests by healthcare professionals (HCPs) compared to remote testing (OR 6.4; 95% CI 5.6, 7.4) and viewed not testing as less preferable than remote testing (OR 0.10; 95% CI 0.09, 0.11). In the second group, which was likely to include 14% of participants, not testing was viewed as less desirable than remote testing (OR 0.56; 95% CI 0.53, 0.59) as were tests by HCPs compared to remote testing (OR 0.23; 95% CI 0.15, 0.36). In both classes, free remote tests instead of each test costing £30 was the test characteristic with the largest impact on the choice of testing option. Participants in the second group were more likely to have never previously tested and to be non-white than participants in the first group. The main study limitations were that the sample was recruited solely via social media, the study advert was viewed only by people expressing an interest in online material used by MSM, and the choices in the experiment were hypothetical rather than observed in the real world. CONCLUSIONS: Our results suggest that preferences in the context we examined are broadly dichotomous. One group, containing the majority of MSM, appears comfortable testing for HIV but prefers face-to-face testing by HCPs rather than remote testing. The other group is much smaller, but contains MSM who are more likely to be at high infection risk. For these people, the availability of remote testing has the potential to significantly increase net testing rates, particularly if provided for free.

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.

Cost-effectiveness of screening for HIV in primary care: a health economics modelling analysis.

BACKGROUND: Early HIV diagnosis reduces morbidity, mortality, the probability of onward transmission, and their associated costs, but might increase cost because of earlier initiation of antiretroviral treatment (ART). We investigated this trade-off by estimating the cost-effectiveness of HIV screening in primary care. METHODS: We modelled the effect of the four-times higher diagnosis rate observed in the intervention arm of the RHIVA2 randomised controlled trial done in Hackney, London (UK), a borough with high HIV prevalence (≥0·2% adult prevalence). We constructed a dynamic, compartmental model representing incidence of infection and the effect of screening for HIV in general practices in Hackney. We assessed cost-effectiveness of the RHIVA2 trial by fitting model diagnosis rates to the trial data, parameterising with epidemiological and behavioural data from the literature when required, using trial testing costs and projecting future costs of treatment. FINDINGS: Over a 40 year time horizon, incremental cost-effectiveness ratios were £22 201 (95% credible interval 12 662-132 452) per quality-adjusted life-year (QALY) gained, £372 207 (268 162-1 903 385) per death averted, and £628 874 (434 902-4 740 724) per HIV transmission averted. Under this model scenario, with UK cost data, RHIVA2 would reach the upper National Institute for Health and Care Excellence cost-effectiveness threshold (about £30 000 per QALY gained) after 33 years. Scenarios using cost data from Canada (which indicate prolonged and even higher health-care costs for patients diagnosed late) suggest this threshold could be reached in as little as 13 years. INTERPRETATION: Screening for HIV in primary care has important public health benefits as well as clinical benefits. We predict it to be cost-effective in the UK in the medium term. However, this intervention might be cost-effective far sooner, and even cost-saving, in settings where long-term health-care costs of late-diagnosed patients in high-prevalence regions are much higher (≥60%) than those of patients diagnosed earlier. Screening for HIV in primary care is cost-effective and should be promoted. FUNDING: NHS City and Hackney, UK Department of Health, National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care.

Long-Term Secondary Care Costs of Endometrial Cancer: A Prospective Cohort Study Nested within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

BACKGROUND: There is limited evidence on the costs of Endometrial Cancer (EC) by stage of disease. We estimated the long-term secondary care costs of EC according to stage at diagnosis in an English population-based cohort. METHODS: Women participating in UKCTOCS and diagnosed with EC following enrolment (2001-2005) and prior to 31st Dec 2009 were identified to have EC through multiple sources. Survival was calculated through data linkage to death registry. Costs estimates were derived from hospital records accessed from Hospital Episode Statistics (HES) with additional patient level covariates derived from case notes and patient questionnaires. Missing and censored data was imputed using Multiple Imputation. Regression analysis of cost and survival was undertaken. RESULTS: 491 of 641 women with EC were included. Five year total costs were strongly dependent on stage, ranging from £9,475 (diagnosis at stage IA/IB) to £26,080 (diagnosis at stage III). Stage, grade and BMI were the strongest predictors of costs. The majority of costs for stage I/II EC were incurred in the first six months after diagnosis while for stage III / IV considerable costs accrued after the first six months. CONCLUSIONS: In addition to survival advantages, there are significant cost savings if patients with EC are detected earlier.

Is increased hepatitis C virus case-finding combined with current or 8-week to 12-week direct-acting antiviral therapy cost-effective in UK prisons? A prevention benefit analysis.

UNLABELLED: Prisoners have a high prevalence of hepatitis C virus (HCV), but case-finding may not have been cost-effective because treatment often exceeded average prison stay combined with a lack of continuity of care. We assessed the cost-effectiveness of increased HCV case-finding and treatment in UK prisons using short-course therapies. A dynamic HCV transmission model assesses the cost-effectiveness of doubling HCV case-finding (achieved through introducing opt-out HCV testing in UK pilot prisons) and increasing treatment in UK prisons compared to status quo voluntary risk-based testing (6% prison entrants/year), using currently recommended therapies (8-24 weeks) or interferon (IFN)-free direct-acting antivirals (DAAs; 8-12 weeks, 95% sustained virological response, £3300/week). Costs (British pounds, £) and health utilities (quality-adjusted life years) were used to calculate mean incremental cost-effectiveness ratios (ICERs). We assumed 56% referral and 2.5%/25% of referred people who inject drugs (PWID)/ex-PWID treated within 2 months of diagnosis in prison. PWID and ex-PWID or non-PWID are in prison an average 4 and 8 months, respectively. Doubling prison testing rates with existing treatments produces a mean ICER of £19,850/quality-adjusted life years gained compared to current testing/treatment and is 45% likely to be cost-effective under a £20,000 willingness-to-pay threshold. Switching to 8-week to 12-week IFN-free DAAs in prisons could increase cost-effectiveness (ICER £15,090/quality-adjusted life years gained). Excluding prevention benefit decreases cost-effectiveness. If >10% referred PWID are treated in prison (2.5% base case), either treatment could be highly cost-effective (ICER<£13,000). HCV case-finding and IFN-free DAAs could be highly cost-effective if DAA cost is 10% lower or with 8 weeks' duration. CONCLUSIONS: Increased HCV testing in UK prisons (such as through opt-out testing) is borderline cost-effective compared to status quo voluntary risk-based testing under a £20,000 willingness to pay with current treatments but likely to be cost-effective if short-course IFN-free DAAs are used and could be highly cost-effective if PWID treatment rates were increased. (Hepatology 2016;63:1796-1808).

What do we know about the cost-effectiveness of HIV preexposure prophylaxis, and is it affordable?

PURPOSE OF REVIEW: The WHO recommends preexposure prophylaxis (PrEP) in populations at substantial risk of HIV. Despite a number of randomized controlled trials demonstrating its efficacy, and several ongoing implementation projects, PrEP is currently only available in a few countries. Modelling studies can provide useful insights into the long-term impact of introducing PrEP in different subgroups of the population. The review summarizes studies that either evaluated the cost-effectiveness or the cost of introducing PrEP, focusing on seven published in the last year. RECENT FINDINGS: These studies used a number of different types of models and investigated the introduction of PrEP in different settings. Among men having sex with men (MSM) in North America, PrEP ranged from being cost-saving (while benefiting population health) to costing US $160,000/quality-adjusted life-year gained. Among heterosexual sero-different couples, it varied from around US $5000 to US $10,000/disability-adjusted life-year averted, when PrEP was used until 6 or 12 months after the HIV-positive partner had initiated antiretroviral therapy (ART) in, respectively, Uganda and South Africa. SUMMARY: Future cost-effectiveness studies of PrEP should consider the HIV incidence, the level of uptake, the effect of its introduction on alternative prevention approaches, and the budget impact of rolling it out.

A review of economic evaluations of diagnostic strategies using imaging in men at risk of prostate cancer.

PURPOSE OF REVIEW: The role of imaging, particularly MRI, in diagnosing clinically significant prostate cancer is the focus of a rapidly developing body of clinical research. We identified five economic evaluations of multiparametric magnetic resonance imaging (mpMRI) for diagnosing prostate cancer which report very different results. This review aims to explain why the reported cost-effectiveness of mpMRI varies so widely. FINDINGS: The studies evaluate the cost-effectiveness of mpMRI within different clinical pathways; before biopsy and after a negative biopsy. Although there were important differences in the questions posed, the studies also employed different assumptions about the impact of prostate cancer and its treatment on survival and quality of life. SUMMARY: This review highlights the need for a better standard of reporting around key modelling assumptions. Also, a wider range of sensitivity analyses should explore the impact of these structural assumptions on the model results, in addition to the more commonly acknowledged uncertainty around data inputs for the model parameters.

Focal therapy: patients, interventions, and outcomes--a report from a consensus meeting.

BACKGROUND: Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. OBJECTIVE: To gather expert opinion on patient selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. DESIGN, SETTING, AND PARTICIPANTS: Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. RESULTS AND LIMITATIONS: Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging-targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3+3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. CONCLUSIONS: The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy. PATIENT SUMMARY: In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer.

Multiparametric MRI followed by targeted prostate biopsy for men with suspected prostate cancer: a clinical decision analysis.

OBJECTIVE: To compare the diagnostic outcomes of the current approach of transrectal ultrasound (TRUS)-guided biopsy in men with suspected prostate cancer to an alternative approach using multiparametric MRI (mpMRI), followed by MRI-targeted biopsy if positive. DESIGN: Clinical decision analysis was used to synthesise data from recently emerging evidence in a format that is relevant for clinical decision making. POPULATION: A hypothetical cohort of 1000 men with suspected prostate cancer. INTERVENTIONS: mpMRI and, if positive, MRI-targeted biopsy compared with TRUS-guided biopsy in all men. OUTCOME MEASURES: We report the number of men expected to undergo a biopsy as well as the numbers of correctly identified patients with or without prostate cancer. A probabilistic sensitivity analysis was carried out using Monte Carlo simulation to explore the impact of statistical uncertainty in the diagnostic parameters. RESULTS: In 1000 men, mpMRI followed by MRI-targeted biopsy 'clinically dominates' TRUS-guided biopsy as it results in fewer expected biopsies (600 vs 1000), more men being correctly identified as having clinically significant cancer (320 vs 250), and fewer men being falsely identified (20 vs 50). The mpMRI-based strategy dominated TRUS-guided biopsy in 86% of the simulations in the probabilistic sensitivity analysis. CONCLUSIONS: Our analysis suggests that mpMRI followed by MRI-targeted biopsy is likely to result in fewer and better biopsies than TRUS-guided biopsy. Future research in prostate cancer should focus on providing precise estimates of key diagnostic parameters.