Pharmacokinetics and pharmacodynamics of intranasal and intramuscular administration of naloxone in working dogs administered fentanyl.

BACKGROUND: Working dogs exposed to narcotics might require reversal in the field. OBJECTIVE: To explore the pharmacokinetic and pharmacodynamic effects of naloxone administered intramuscularly (IM) or intranasally (IN) to reverse fentanyl sedation in working dogs. ANIMALS: Ten healthy, working dogs aged 1.7 ± 1 year and weighing 26 ± 3 kg. METHODS: In this randomized, controlled cross-over study dogs received either 4 mg of naloxone IN or IM 10 minutes after fentanyl (0.3 mg IV) administration. Sedation was assessed at baseline and 5 minutes after fentanyl administration, then at 5, 10, 15, 20, 25, 30, 60 and 120 minutes after reversal with naloxone. Blood samples for naloxone detection were obtained at 0, 5, 10, 30, 60 and 120 minutes. Pharmacokinetic parameters and sedation scores were compared between IM and IN naloxone groups. RESULTS: There was a significant increase in sedation score from baseline (0.25 [-4 to 1] IM; 0 [-2 to 1] IN) after fentanyl administration (11 [5-12] IM; 9.25 [4-11] IN), followed by a significant reduction at 5 (0.5 [-0.5 to 1.5] IM; 1.25 [-1.5 to 4.5] IN) through 120 minutes (-0.5 [-2 to 1] IM; 0 [-4.5 to 1] IN) after reversal with naloxone. Route of administration had no significant effect on sedation score. Maximum plasma concentration was significantly lower after IN administration (11.7 [2.8-18.8] ng/mL IN, 36.7 [22.1-56.4] ng/mL IM, P < .001) but time to reach maximum plasma concentration was not significantly different from IM administration. CONCLUSION AND CLINICAL IMPORTANCE: Although IM administration resulted in higher naloxone plasma concentrations compared to IN, reversal of sedation was achieved via both routes after administration of therapeutic doses of fentanyl.

Outcomes in Ankle Replacement Study (OARS).

Aims: The aim of this study was to capture 12-month outcomes from a representative multicentre cohort of patients undergoing total ankle arthroplasty (TAA), describe the pattern of patient-reported outcome measures (PROMs) at 12 months, and identify predictors of these outcome measures. Methods: Patients listed for a primary TAA at 19 NHS hospitals between February 2016 and October 2017 were eligible. PROMs data were collected preoperatively and at six and 12 months including: Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ (foot and ankle)) and the EuroQol five-dimension five-level questionnaire (EQ-5D-5L). Radiological pre- and postoperative data included Kellgren-Lawrence score and implant position measurement. This was supplemented by data from the National Joint Registry through record linkage to determine: American Society of Anesthesiologists (ASA) grade at index procedure; indication for surgery, index ankle previous fracture; tibial hind foot alignment; additional surgery at the time of TAA; and implant type. Multivariate regression models assessed outcomes, and the relationship between MOXFQ and EQ-5D-5L outcomes, with patient characteristics. Results: Data from 238 patients were analyzed. There were significant improvements in MOXFQ and EQ-5D-5L among people who underwent TAA at six- and 12-month assessments compared with preoperative scores (p < 0.001). Most improvement occurred between preoperative and six months, with little further improvement at 12 months. A greater improvement in MOXFQ outcome postoperatively was associated with older age and more advanced radiological signs of ankle osteoarthritis at baseline. Conclusion: TAA significantly benefits patients with end-stage ankle disease. The lack of substantial further overall change between six and 12 months suggests that capturing PROMs at six months is sufficient to assess the success of the procedure. Older patients and those with advanced radiological disease had the greater gains. These outcome predictors can be used to counsel younger patients and those with earlier ankle disease on the expectations of TAA.

Associations between neighbourhood social cohesion and subjective well-being in two different informal settlement types in Delhi, India: a quantitative cross-sectional study.

OBJECTIVES: To evaluate the relationships between neighbourhood cohesion and subjective well-being (SWB) in two different informal settlement types. DESIGN: Cross-sectional analysis of a community-based survey. SETTING: Communities in two districts, Sanjay Colony, Okhla Phase II and Bhalswa in Delhi, India. PARTICIPANTS: 328 residents in Bhalswa and 311 from Sanjay Colony. MEASUREMENTS: Neighbourhood social cohesion scale measured on an 18-point scale and the SWB scale made up of four subjective measures-hedonic, eudaemonic, evaluative and freedom of choice. Sociodemographic characteristics and trust were used as covariates. RESULTS: In both neighbourhood types there was a statistically significant positive bivariate correlation between neighbourhood cohesion and SWB (Sanjay: r=0.145, p<0.05; Bhalswa: r=0.264, p<0.01). Trust and neighbourhood cohesion were strongly correlated (Sanjay: r=0.618, p<0.01; Bhalswa: r=0.533, p<0.01) and the longer the resident had lived in the community the greater the feeling of neighbourhood cohesion (Sanjay: r=0.157, p<0.01; Bhalswa: r=0.171, p<0.05). Only in the resettlement colony (Bhalswa) was SWB negatively correlated with length of residency (r=-0.117, p<0.05). Residents who chose their settlement type (Sanjay residents) were 22.5 percentage points (pp) more likely to have a feeling of belonging to their neighbourhood than residents that had been resettled (Bhalswa) (Cohen's d effect size 0.45). Sanjay residents had a greater likelihood to feel more satisfied with life (4.8 pp, p<0.01) and having greater perceived freedom of choice (4.8 pp, p<0.01). CONCLUSIONS: Our findings contribute to the general knowledge about neighbourhood cohesion and SWB within different informal settlement types in a mega-city such as New Delhi, India. Interventions that promote sense of belonging, satisfaction with life and freedom of choice have the potential to significantly improve people's well-being.

Should compromised first permanent molar teeth in children be routinely removed? A health economics analysis.

OBJECTIVE: To evaluate the cost-effectiveness of retaining one or more compromised first permanent molars (cFPMs) affected by dental caries or enamel hypomineralization, compared to timely extraction, in children aged 8 years. METHODS: A Markov model was developed to simulate the lifetime of a cFPM. Two management strategies were compared: extraction facilitating spontaneous space closure or maintenance of teeth with restorations. Ten health states were utilized to capture long-term outcomes including various tooth restorations, prostheses or a retained gap at the cFPM site. Outcomes were expressed as Quality Adjusted Tooth-Years (QATYs). The model was informed by survey data on patient preferences for treatment outcomes and UK data on costs. Discounted costs and QATYs were calculated over 62 years. RESULTS: Regardless of the number of cFPMs, retaining cFPMs was more effective than early removal, generating an additional 2.3 QATYs per cFPM. Early removal of one or two cFPM under general anaesthetic (GA) was more expensive than retention and hence never cost-effective. Retaining a cFPM was more expensive than early removal under local anaesthesia or where four cFPMs were extracted under GA. In these cases, retaining cFPMs was cost-effective if a QATY was valued at £100 or £35, respectively. Results were robust to sensitivity analysis. CONCLUSION: Preserving a cFPM was more cost-effective than the early loss of one, or two cFPMs under GA. Preservation of four cFPMs was cost-effective if sufficient value was placed on a QATY. These findings can guide clinical practice on management of cFPMs alongside patient/payer values on maintaining teeth.

Foucault and Hayek on public health and the road to serfdom.

This paper draws on the work of Michel Foucault and Friedrich Hayek to understand threats to personal and enterprise freedom, arising from public health governance. Whereas public choice theory examines the incentives these institutions provide to agents, the analysis here understands those incentives as framed by discursive social constructions that affect the identity, power, and positionality of different actors. It shows how overlapping discourses of scientific rationalism may generate a 'road to serfdom' narrowing freedom of action and expression across an expanding terrain. As such, the paper contributes to the growing literature emphasising the importance of narratives, stories and metaphors as shaping political economic action in ways feeding through to outcomes and institutions.

Cost-effectiveness of alternative minimum recall intervals between whole blood donations.

BACKGROUND: The INTERVAL trial showed shorter inter-donation intervals could safely increase the frequency of whole-blood donation. We extended the INTERVAL trial to consider the relative cost-effectiveness of reduced inter-donation intervals. METHODS: Our within-trial cost-effectiveness analysis (CEA) used data from 44,863 whole-blood donors randomly assigned to 12, 10 or 8 week (males), and 16, 14 or 12 week inter-donation intervals (females). The CEA analysed the number of whole-blood donations, deferrals including low- haemoglobin deferrals, and donors' health-related quality of life (QoL) to report costs and cost-effectiveness over two years. FINDINGS: The mean number of blood donation visits over two years was higher for the reduced interval strategies, for males (7.76, 6.60 and 5.68 average donations in the 8-, 10- and 12- week arms) and for females (5.10, 4.60 and 4.01 donations in the 12-, 14- and 16- week arms). For males, the average rate of deferral for low haemoglobin per session attended, was 5.71% (8- week arm), 3.73% (10- week), and 2.55% (12- week), and for females the rates were: 7.92% (12-week), 6.63% (14- week), and 5.05% (16- week). Donors' QoL was similar across strategies, although self-reported symptoms were increased with shorter donation intervals. The shorter interval strategies increased average cost, with incremental cost-effectiveness ratios of £9.51 (95% CI 9.33 to 9.69) per additional whole-blood donation for the 8- versus 12- week interval for males, and £10.17 (95% CI 9.80 to 10.54) for the 12- versus 16- week interval arm for females. CONCLUSIONS: Over two years, reducing the minimum donation interval could provide additional units of whole-blood at a small additional cost, including for those donor subgroups whose blood type is in relatively high demand. However, the significance of self-reported symptoms needs to be investigated further before these policies are expanded.

Key Drivers and Facilitators of the Choice to Use mHealth Technology in People With Neurological Conditions: Observational Study.

BACKGROUND: There is increasing interest in the potential uses of mobile health (mHealth) technologies, such as wearable biosensors, as supplements for the care of people with neurological conditions. However, adherence is low, especially over long periods. If people are to benefit from these resources, we need a better long-term understanding of what influences patient engagement. Previous research suggests that engagement is moderated by several barriers and facilitators, but their relative importance is unknown. OBJECTIVE: To determine preferences and the relative importance of user-generated factors influencing engagement with mHealth technologies for 2 common neurological conditions with a relapsing-remitting course: multiple sclerosis (MS) and epilepsy. METHODS: In a discrete choice experiment, people with a diagnosis of MS (n=141) or epilepsy (n=175) were asked to select their preferred technology from a series of 8 vignettes with 4 characteristics: privacy, clinical support, established benefit, and device accuracy; each of these characteristics was greater or lower in each vignette. These characteristics had previously been emphasized by people with MS and or epilepsy as influencing engagement with technology. Mixed multinomial logistic regression models were used to establish which characteristics were most likely to affect engagement. Subgroup analyses explored the effects of demographic factors (such as age, gender, and education), acceptance of and familiarity with mobile technology, neurological diagnosis (MS or epilepsy), and symptoms that could influence motivation (such as depression). RESULTS: Analysis of the responses to the discrete choice experiment validated previous qualitative findings that a higher level of privacy, greater clinical support, increased perceived benefit, and better device accuracy are important to people with a neurological condition. Accuracy was perceived as the most important factor, followed by privacy. Clinical support was the least valued of the attributes. People were prepared to trade a modest amount of accuracy to achieve an improvement in privacy, but less likely to make this compromise for other factors. The type of neurological condition (epilepsy or MS) did not influence these preferences, nor did the age, gender, or mental health status of the participants. Those who were less accepting of technology were the most concerned about privacy and those with a lower level of education were prepared to trade accuracy for more clinical support. CONCLUSIONS: For people with neurological conditions such as epilepsy and MS, accuracy (ie, the ability to detect symptoms) is of the greatest interest. However, there are individual differences, and people who are less accepting of technology may need far greater reassurance about data privacy. People with lower levels of education value greater clinician involvement. These patient preferences should be considered when designing mHealth technologies.

Healthcare utilization and costs in chronic cough.

BACKGROUND: Chronic cough is a common reason for medical consultations and is associated with considerable physical and psychological morbidity. This study investigated healthcare use and cost in chronic cough and assessed its relationship with cough severity, health status, objective cough frequency (CF), and anxiety and depression. METHODS: This was a prospective study of consecutive patients with chronic cough from a specialist clinic who completed a cough severity visual analogue scale (VAS), cough-specific health status (Leicester Cough Questionnaire; LCQ) and general health status EuroQol EQ-5D-5L, Generalized Anxiety Disorder (GAD7), Patient Health Questionnaire (PHQ9), and 24-hour objective CF monitoring with Leicester Cough Monitor (LCM). Case notes were reviewed for cough-specific healthcare use 12 months before and after the first cough clinic consultation. Resource use included general practitioner and hospital clinic visits, investigations, and treatments. Unit costs for healthcare use were derived predominantly from National Health Service Reference Costs. RESULTS: One hundred participants with chronic cough were recruited (69% female, median duration 3 years, mean age 58 years). The diagnoses of cough were unexplained (57%), refractory (27%), and other (16%). Cough severity, health status, and CF were: median (IQR) VAS = 59.5 (30-79) mm, mean (SD) LCQ = 11.9 (4.0), mean (SD) EQ-5D-5L = 0.846 (0.178), and geometric mean (SD) CF = 15.3 (2.5) coughs/hr, respectively. The mean (SD) total cost per individual for cough-related healthcare utilization was £1,663 (747). Diagnostic investigations were the largest contributor to cost (63%), followed by cough clinic consultations (25%). In multivariate analysis, anxiety (GAD7) and cough-related health status (LCQ) were associated with increased cost (p ≤.001 and .037). CONCLUSION: Healthcare cost associated with chronic cough are largely due to diagnostic investigations and clinic consultations. The predictors of costs were health status (LCQ) and anxiety. Further studies should investigate the optimal management protocols for patients with chronic cough.

Cost-effectiveness in diagnosis of stable angina patients: a decision-analytical modelling approach.

OBJECTIVE: Given recent data on published diagnostic accuracies, this study sought to determine the most cost-effective diagnostic strategy for detection of significant coronary artery disease (CAD) in stable angina patients using invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the reference standard. METHODS: A probabilistic decision-analytical model was developed which modelled a cohort of patients with stable angina. We investigated 17 diagnostic strategies between standalone and combination of different imaging tests to establish a correct diagnosis of CAD, using no testing as the baseline reference. These tests included CT coronary angiography (CTCA), stress echocardiography, CT-based FFR, single-photon emission computed tomography (SPECT), cardiovascular magnetic resonance (CMR), positron emission tomography, ICA, and ICA with FFR. Incremental cost-effectiveness ratios were calculated as the additional cost per correct diagnosis. RESULTS: SPECT followed by CTCA and ICA-FFR is the most cost-effective strategy between a cost-effectiveness threshold (CET) value of £1000-£3000 per correct diagnosis. CMR followed by CTCA and ICA-FFR is cost-effective within a CET range of £3000-£17 000 per correct diagnosis. CMR and ICA-FFR is cost-effective within a CET range of £17 000-£24 000. ICA-FFR as first line is the most-cost effective if the CET value exceeds the £24 000 per correct diagnosis. Sensitivity analysis showed that direct ICA-FFR may be cost-effective in patients with a high pre-test probability of CAD. CONCLUSION: First-line testing with functional imaging is cost-effective at low to intermediate value of correct diagnosis in patients with low to intermediate risk of CAD. ICA is not cost effective although ICA-FFR may be at higher CET.

Transition from esophagectomy to endoscopic therapy for early esophageal cancer.

BACKGROUND: To assess the outcomes of patients with early esophageal cancer and high-grade dysplasia comparing esophagectomy, the historical treatment of choice, to endoscopic eradication therapy (EET). METHODS: Retrospective cohort study of consecutive patients with early esophageal cancer/high-grade dysplasia, treated between 2000 and 2018 at a tertiary center. Primary outcomes were all-cause and disease-specific mortality assessed by multivariable Cox regression and a propensity score matching sub analysis, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, tumor grade (G1/2 vs. G3), tumor stage, and lymphovascular invasion. Secondary outcomes included complications, hospital stay, and overall costs. RESULTS: Among 269 patients, 133 underwent esophagectomy and 136 received EET. Adjusted survival analysis showed no difference between groups regarding all-cause mortality (HR 1.85, 95% CI 0.73, 4.72) and disease-specific mortality (HR 1.10, 95% CI 0.26, 4.65). In-hospital and 30-day mortality was 0% in both groups. The surgical group had a significantly higher rate of complications (Clavien-Dindo ≥3 26.3% vs. endoscopic therapy 0.74%), longer in-patient stay (median 14 vs. 0 days endoscopic therapy) and higher hospital costs(£16 360 vs. £8786 per patient). CONCLUSION: This series of patients treated during a transition period from surgery to EET, demonstrates a primary endoscopic approach does not compromise oncological outcomes with the benefit of fewer complications, shorter hospital stays, and lower costs compared to surgery. It should be available as the gold standard treatment for patients with early esophageal cancer. Those with adverse prognostic features may still benefit from esophagectomy.

Cost-effectiveness analysis of hemodialysis plus hemoperfusion versus hemodialysis alone in adult patients with end-stage renal disease in China.

BACKGROUND: This study evaluates the cost-effectiveness of hemodialysis (HD) plus hemoperfusion (HP) with HD alone in adult patients with end-stage renal disease (ESRD) in China. METHODS: A Markov model was constructed to assess the cost-effectiveness of interventions over a lifetime horizon. Model parameters were informed by the HD/HP trial, the first randomized, open-label multicenter trial comparing survival outcomes and incidence of cardiovascular disease (CVD) for HD + HP versus HD alone, and supplemented by published literature and expert opinion. The primary outcome was the incremental cost-effectiveness ratio (ICER) with respect to quality adjusted life-years (QALY). The robustness of the results was examined in extensive sensitivity analyses. Analyses were conducted from a healthcare perspective. Costs were reported in both Chinese Renminbi (RMB) and US Dollars (USD) in 2019 values. RESULTS: The base case ICER of HD + HP is RMB 174,486 (USD 25,251) per QALY, which is lower than the RMB 212,676 (USD 30,778) willingness-to-pay threshold of three times Gross Domestic Product. This conclusion is sensitive to the mortality for patients with no severe CVD events, the incidence of CVD events, and the cost of HP and HD. At a willingness-to-pay threshold of RMB 212,676 (USD 30,778) per QALY gained, the probability that HD + HP is cost-effective is 58%. CONCLUSIONS: Our results indicate a potential for HD + HP to be cost-effective for patients with ESRD. Further evidence on the longer-term impact of HD + HP on CVD event rates and mortality unrelated to CVD is needed to robustly demonstrate the cost-effectiveness of HD + HP. TRIAL REGISTRATION: The HD/HP trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-16009332).

Protocol for A randomised feasibility trial comparing fluoride interventions to prevent dental decay in older people in care homes (FInCH trial).

BACKGROUND: The number and proportion of older people globally is growing faster than that of any other age group. At the same time the number of people retaining some of their own teeth is rising. There significant differences between those living in care and their community dwelling peers, with evidence showing those in care having fewer teeth and significantly higher levels of dental decay. There are numerous Cochrane reviews linking the use of fluoride to a reduction in dental decay, however, the majority of research on effectiveness has been conducted on children and consequently, children and adolescents tend to be the main recipients of fluoride interventions. There are to date no studies comparing the effectiveness of fluoride interventions in older people in care homes in the UK. However, prior to developing an appropriate protocol for full-scale trial comparing clinical effectiveness of fluoride interventions, there are a number of trial feasibility and statistical parameters that need to be clarified. METHODS: This trial is a single centre, multi-site randomised controlled assessor blind parallel group (three groups) trial, with the primary objective of establishing the feasibility, practicability and compliance of fluoride interventions to prevent dental decay in care homes. Secondary and tertiary objectives will aim to explore the acceptability of the interventions from resident, care home and dental services perspectives, and estimate the efficacy of the three different fluoride treatments. DISCUSSION: This feasibility trial will produce new knowledge and add value to a landscape that is under researched. Although the efficacy of fluoride interventions is proven, the feasibility of dental research and prevention in this vulnerable group and in the complex care home setting is novel. This work will not only add to our understanding of the interface of dental care and social care but will also contribute to our broader understanding on undertaking research in care home settings. Dental care for older people has been a longstanding issue, and the events of this past year has shone a light on the vulnerabilities of those residing in care homes and so this research is landing at a pivotal time. Trial registration EudraCT Registration 2017-002248-34. Registered 20th February 2018 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-002248-34 .

Disease Burden Attributable to the First Wave of COVID-19 in China and the Effect of Timing on the Cost-Effectiveness of Movement Restriction Policies.

OBJECTIVES: Movement restriction policies (MRPs) are effective in preventing/delaying COVID-19 transmission but are associated with high societal cost. This study aims to estimate the health burden of the first wave of COVID-19 in China and the cost-effectiveness of early versus late implementation of MRPs to inform preparation for future waves. METHODS: The SEIR (susceptible, exposed, infectious, and recovered) modeling framework was adapted to simulate the health and cost outcomes of initiating MRPs at different times: rapid implementation (January 23, the real-world scenario), delayed by 1 week, delayed by 2 weeks, and delayed by 4 weeks. The end point was set as the day when newly confirmed cases reached zero. Two costing perspectives were adopted: healthcare and societal. Input data were obtained from official statistics and published literature. The primary outcomes were disability-adjusted life-years, cost, and net monetary benefit. Costs were reported in both Chinese renminbi (RMB) and US dollars (USD) at 2019 values. RESULTS: The first wave of COVID-19 in China resulted in 38 348 disability adjusted life-years lost (95% CI 19 417-64 130) and 2639 billion RMB losses (95% CI 1347-4688). The rapid implementation strategy dominated all other delayed strategies. This conclusion was robust to all scenarios tested. At a willingness-to-pay threshold of 70 892 RMB (the national annual GDP per capita) per disability-adjusted life-year saved, the probability for the rapid implementation to be the optimal strategy was 96%. CONCLUSIONS: Early implementation of MRPs in response to COVID-19 reduced both the health burden and societal cost and thus should be used for future waves of COVID-19.

Economic burden of COVID-19, China, January-March, 2020: a cost-of-illness study.

OBJECTIVE: To estimate the economic cost of coronavirus disease 19 (COVID-19) in 31 provincial-level administrative regions and in total, in China. METHODS: We used data from government reports, clinical guidelines and other publications to estimate the main cost components of COVID-19 during 1 January-31 March 2020. These components were: identification and diagnosis of close contacts; suspected cases and confirmed cases of COVID-19; treatment of COVID-19 cases; compulsory quarantine of close contacts and suspected cases; and productivity losses for all affected residents. Primary outcomes were total health-care and societal costs. FINDINGS: The total estimated health-care and societal costs associated with COVID-19 were 4.26 billion Chinese yuan (¥; 0.62 billion United States dollars, US$) and ¥ 2646.70 billion (US$ 383.02 billion), respectively. Inpatient care accounted for 44.2% (¥ 0.95 billion/¥ 2.15 billion) of routine health-care costs followed by medicines, accounting for 32.5% (¥ 0.70 billion/¥ 2.15 billion). Productivity losses accounted for 99.8% (¥ 2641.61 billion/¥ 2646.70 billion) of societal costs, which were mostly attributable to the effect of movement-restriction policies on people who did not have COVID-19. Societal costs were most sensitive to salary costs and number of working days lost due to movement-restriction policies. Hubei province had the highest health-care cost while Guangdong province had the highest societal cost. CONCLUSION: Our results highlight the high economic burden of the COVID-19 outbreak in China. The control measures to prevent the spread of disease resulted in substantial costs from productivity losses amounting to 2.7% (US$ 382.29 billion/US$ 14.14 trillion) of China's annual gross domestic product.

A Position Statement on the Utility of Interval Imaging in Standard of Care Brain Tumour Management: Defining the Evidence Gap and Opportunities for Future Research.

OBJECTIV E: To summarise current evidence for the utility of interval imaging in monitoring disease in adult brain tumours, and to develop a position for future evidence gathering while incorporating the application of data science and health economics. METHODS: Experts in 'interval imaging' (imaging at pre-planned time-points to assess tumour status); data science; health economics, trial management of adult brain tumours, and patient representatives convened in London, UK. The current evidence on the use of interval imaging for monitoring brain tumours was reviewed. To improve the evidence that interval imaging has a role in disease management, we discussed specific themes of data science, health economics, statistical considerations, patient and carer perspectives, and multi-centre study design. Suggestions for future studies aimed at filling knowledge gaps were discussed. RESULTS: Meningioma and glioma were identified as priorities for interval imaging utility analysis. The "monitoring biomarkers" most commonly used in adult brain tumour patients were standard structural MRI features. Interval imaging was commonly scheduled to provide reported imaging prior to planned, regular clinic visits. There is limited evidence relating interval imaging in the absence of clinical deterioration to management change that alters morbidity, mortality, quality of life, or resource use. Progression-free survival is confounded as an outcome measure when using structural MRI in glioma. Uncertainty from imaging causes distress for some patients and their caregivers, while for others it provides an important indicator of disease activity. Any study design that changes imaging regimens should consider the potential for influencing current or planned therapeutic trials, ensure that opportunity costs are measured, and capture indirect benefits and added value. CONCLUSION: Evidence for the value, and therefore utility, of regular interval imaging is currently lacking. Ongoing collaborative efforts will improve trial design and generate the evidence to optimise monitoring imaging biomarkers in standard of care brain tumour management.

Addressing the low consumption of fruit and vegetables in England: a cost-effectiveness analysis of public policies.

BACKGROUND: Most adults do not meet the recommended intake of five portions per day of fruit and vegetables (F&V) in England, but economic analyses of structural policies to change diet are sparse. METHODS: Using published data from official statistics and meta-epidemiological studies, we estimated the deaths, years-of-life lost (YLL) and the healthcare costs attributable to consumption of F&V below the recommended five portions per day by English adults. Then, we estimated the cost-effectiveness from governmental and societal perspectives of three policies: a universal 10% subsidy on F&V, a targeted 30% subsidy for low-income households and a social marketing campaign (SMC). FINDINGS: Consumption of F&V below the recommended five portions a day accounted for 16 321 [10 091-23 516] deaths and 238 767 [170 350-311 651] YLL in England in 2017, alongside £705 951 [398 761-1 061 559] million in healthcare costs. All policies would increase consumption and reduce the disease burden attributable to low intake of F&V. From a societal perspective, the incremental cost-effectiveness ratios were £22 891 [22 300-25 079], £16 860 [15 589-19 763] and £25 683 [25 237-28 671] per life-year saved for the universal subsidy, targeted subsidy and SMC, respectively. At a threshold of £20 000 per life-year saved, the likelihood that the universal subsidy, the targeted subsidy and the SMC were cost-effective was 84%, 19% and 5%, respectively. The targeted subsidy would additionally reduce inequalities. CONCLUSIONS: Low intake of F&V represents a heavy health and care burden in England. All dietary policies can improve consumption of F&V, but only a targeted subsidy to low-income households would most likely be cost-effective.

Implementation of early psychosis services in Latin America: A scoping review.

AIM: The evidence of the effectiveness and cost-effectiveness of early intervention for psychosis (EIP) services has motivated their implementation worldwide. However, complex interventions of such EIP services require local adaptations to successfully match population needs and cultural differences. Latin America is a heterogenous region where EIP services are progressively being adopted. Our aim is to map such initiatives in the region with a focus on implementation outcomes. METHODS: A scoping review following the Preferred Reporting Items for Systematic review and Meta-Analysis extension for Scoping Reviews guidelines was conducted. International and regional databases were searched for publications describing EIP programmes in the region. Besides mapping the services, we described implementation outcomes based on the Standards for Reporting Implementation Studies Checklist. RESULTS: Ten articles describing seven EIP initiatives from the region were found. Four countries were represented: Argentina, Brazil, Chile and Mexico. The implementation outcomes reporting was heterogenous, although it was possible to ascertain EIP services are feasible and adequate for the region's context. Also, there is some evidence of effectiveness in terms of reducing hospitalizations and improving symptoms. Information about fidelity measures was scarce and there was no information about costs or cost-effectiveness. CONCLUSIONS: Only a small proportion of Latin American countries have adopted EIP services. Although these programmes seem to be feasible and effective, data on other implementation outcomes, such as fidelity, cultural appropriateness, cost-effectiveness and affordability are not available. This might in part explain why this effective approach has not been yet scaled-up at nationwide levels.

Costs of Early Invasive Breast Cancer in England Using National Patient-Level Data.

OBJECTIVES: This study aimed to use patient-level data to provide up-to-date estimates of early invasive breast cancer care costs by stage in England and to explore to what extent these costs varied based on patients' ages and geographic regions. METHODS: This study identified women aged 50 years and older who had been diagnosed with early invasive breast cancer between January 1, 2014, and December 31, 2015, using linked cancer registrations and routine hospital data sets generated from the usual care for all National Health Service trusts in England. Cost estimates were derived from hospital records in Hospital Episodes Statistics with additional chemotherapy and radiotherapy information from the national data sets. We fitted general linear regression models to analyze the cost data. The model that best fit the data was selected using the model selection criteria of Akaike information criterion. RESULTS: 55 662 women with early invasive breast cancer in England were included. The generalized linear model with log-gamma distribution fit the data best. The costs of breast cancer care for 1 year after diagnosis were strongly dependent on stage at diagnosis, controlling for other covariates. The estimated average per-patient hospital-related costs were £5167 at stage I, £7613 at stage II, and £13 330 at stage IIIA. Costs decreased with increasing age (P < .001) and varied across region (P < .001), deprivation level (P < .001), referral source (P < .01), presence of comorbidities (P< .001), and tumor receptor (ER/PR/HER2) status (P < .001). CONCLUSIONS: In England, the costs of breast cancer care increased with advancing stage of the disease at diagnosis. Breast cancer costs varied by age and geographic region.