Model-based economic evaluation of the effectiveness of "'Hypos' can strike twice", a leaflet-based ambulance clinician referral intervention to prevent recurrent hypoglycaemia.

"'Hypos' can strike twice" (HS2) is a pragmatic, leaflet-based referral intervention designed for administration by clinicians of the emergency medical services (EMS) to people they have attended and successfully treated for hypoglycaemia. Its main purpose is to encourage the recipient to engage with their general practitioner or diabetic nurse in order that improvements in medical management of their diabetes may be made, thereby reducing their risk of recurrent hypoglycaemia. Herein we build a de novo economic model for purposes of incremental analyses to compare, in 2018-19 prices, HS2 against standard care for recurrent hypoglycaemia in the fortnight following the initial attack from the perspective of the UK National Health Service (NHS). We found that per patient NHS costs incurred by people receiving the HS2 intervention over the fortnight following an initial hypoglycaemia average £49.79, and under standard care costs average £40.50. Target patient benefit assessed over that same period finds the probability of no recurrence of hypoglycaemia averaging 42.4% under HS2 and 39.4% under standard care, a 7.6% reduction in relative risk. We find that implementing HS2 will cost the NHS an additional £309.36 per episode of recurrent hypoglycaemia avoided. Contrary to the favourable support offered in Botan et al., we conclude that in its current form the HS2 intervention is not a cost-effective use of NHS resources when compared to standard NHS care in reducing the risk of hypoglycaemia recurring within a fortnight of an initial attack that was resolved at-scene by EMS ambulance clinicians.

Optimising ambulance conveyance rates and staff costs by adjusting proportions of rapid-response vehicles and dual-crewed ambulances: an economic decision analytical modelling study.

AIM: To model optimum proportions of dual-crewed ambulances (DCAs) and rapid-response vehicles (RRVs) in Ambulance Trusts with a view to generating a policy brief for one Ambulance Trust and a modelling tool for other Trusts on the strategic procurement and allocation of emergency vehicle (EV) resources. METHODS: Historical EV assignments for 12 months of emergency calls in 2019 were provided by an NHS Ambulance Trust and analysed for backup, see and treat, and patient to hospital conveyance. Unit costs were derived for paramedics and technicians using Agenda for Change pay rates. Time cycles were assigned for RRV and DCA attendances and unit costs assigned to these. Information was put into a decision analytical model to estimate the costs and numbers of vehicles attending incidents based on relative proportions of available RRVs and DCAs. RESULTS: Of 711 992 calls attended by 837 107 EVs, 514 766 (72.3%) required at least one emergency department conveyance. The rate of conveyance was significantly lower when RRVs arrived first on the scene. 27 883 out of 529 693 (5.3%) DCAs first arriving at an incident required some backup, and this was also factored into the model. Modelling demonstrated high conveyance rates were counterproductive when increasing the relative proportions of RRVs to DCAs. For example, with conveyance rates of 65%, increasing the RRVs increased the cost and numbers of vehicles attending per incident. At lower conveyance rates, however, there was a levelling around 30% where it could become cost-effective to increase the relative proportions of RRVs to DCAs. CONCLUSION: At current overall conveyance rates, there is no benefit in increasing the relative proportions of RRVs to DCAs unless additional benefits can be realised that bring the conveyance rates down.

Helicobacter pylori eradication for primary prevention of peptic ulcer bleeding in older patients prescribed aspirin in primary care (HEAT): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Peptic ulcers in patients receiving aspirin are associated with Helicobacter pylori infection. We aimed to investigate whether H pylori eradication would protect against aspirin-associated ulcer bleeding. METHODS: We conducted a randomised, double-blind, placebo-controlled trial (Helicobacter Eradication Aspirin Trial [HEAT]) at 1208 primary care centres in the UK, using routinely collected clinical data. Eligible patients were aged 60 years or older who were receiving aspirin at a daily dose of 325 mg or less (with four or more 28-day prescriptions in the past year) and had a positive C13 urea breath test for H pylori at screening. Patients receiving ulcerogenic or gastroprotective medication were excluded. Participants were randomly assigned (1:1) to receive either a combination of oral clarithromycin 500 mg, metronidazole 400 mg, and lansoprazole 30 mg (active eradication), or oral placebo (control), twice daily for 1 week. Participants, their general practitioners and health-care providers, and the research nurses, trial team, adjudication committee, and analysis team were all masked to group allocation throughout the trial. Follow-up was by scrutiny of electronic data in primary and secondary care. The primary outcome was time to hospitalisation or death due to definite or probable peptic ulcer bleeding, and was analysed by Cox proportional hazards methods in the intention-to-treat population. This trial is registered with EudraCT, 2011-003425-96. FINDINGS: Between Sept 14, 2012, and Nov 22, 2017, 30 166 patients had breath testing for H pylori, 5367 had a positive result, and 5352 were randomly assigned to receive active eradication (n=2677) or placebo (n=2675) and were followed up for a median of 5·0 years (IQR 3·9-6·4). Analysis of the primary outcome showed a significant departure from proportional hazards assumptions (p=0·0068), requiring analysis over separate time periods. There was a significant reduction in incidence of the primary outcome in the active eradication group in the first 2·5 years of follow-up compared with the control group (six episodes adjudicated as definite or probable peptic ulcer bleeds, rate 0·92 [95% CI 0·41-2·04] per 1000 person-years vs 17 episodes, rate 2·61 [1·62-4·19] per 1000 person-years; hazard ratio [HR] 0·35 [95% CI 0·14-0·89]; p=0·028). This advantage remained significant after adjusting for the competing risk of death (p=0·028) but was lost with longer follow-up (HR 1·31 [95% CI 0·55-3·11] in the period after the first 2·5 years; p=0·54). Reports of adverse events were actively solicited; taste disturbance was the most common event (787 patients). INTERPRETATION: H pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this might not be sustained in the long term. FUNDING: National Institute for Health and Care Research Health Technology Assessment.

Evaluation of the effectiveness and costs of inhaled methoxyflurane versus usual analgesia for prehospital injury and trauma: non-randomised clinical study.

BACKGROUND: We aimed to investigate clinical benefits and economic costs of inhaled methoxyflurane when used by ambulance staff for prehospital emergency patients with trauma. Comparison is to usual analgesic practice (UAP) in the UK in which patient records were selected if treatment had been with Entonox® or intravenous morphine or intravenous paracetamol. METHODS: Over a 12-month evaluation period, verbal numerical pain scores (VNPS) were gathered from adults with moderate to severe trauma pain attended by ambulance staff trained in administering and supplied with methoxyflurane. Control VNPS were obtained from ambulance database records of UAP in similar patients for the same period. Statistical modelling enabled comparisons of methoxyflurane to UAP, where we employed an Ordered Probit panel regression model for pain, linked by observational rules to VNPS. RESULTS: Overall, 96 trained paramedics and technicians from the East Midlands Ambulance Service NHS Trust (EMAS) prepared 510 doses of methoxyflurane for administration to a total of 483 patients. Comparison data extracted from the EMAS database of UAP episodes involved: 753 patients using Entonox®, 802 patients using intravenous morphine, and 278 patients using intravenous paracetamol. Modelling results included demonstration of faster pain relief with inhaled methoxyflurane (all p-values < 0.001). Methoxyflurane's time to achieve maximum pain relief was estimated to be significantly shorter: 26.4 min (95%CI 25.0-27.8) versus Entonox® 44.4 min (95%CI 39.5-49.3); 26.5 min (95%CI 25.0-27.9) versus intravenous morphine 41.8 min (95%CI 38.9-44.7); 26.5 min (95%CI 25.1-28.0) versus intravenous paracetamol 40.8 (95%CI 34.7-46.9). Scenario analyses showed that durations spent in severe pain were significantly less for methoxyflurane. Costing scenarios showed the added benefits of methoxyflurane were achieved at higher cost, eg versus Entonox® the additional cost per treated patient was estimated to be £12.30. CONCLUSION: When administered to adults with moderate or severe pain due to trauma inhaled methoxyflurane reduced pain more rapidly and to a greater extent than Entonox® and parenteral analgesics. Inclusion of inhaled methoxyflurane to the suite of prehospital analgesics provides a clinically useful addition, but one that is costlier per treated patient.

Investigating the cost-effectiveness of three cessation interventions on a national scale using the Economics of Smoking in Pregnancy (ESIP) decision analytical model.

AIM: To measure the cost-effectiveness of adding text message (TMB), exercise (EB) and abstinent-contingent financial incentive-based (CFIB) stop smoking interventions to standard smoking cessation support for pregnant women in England. DESIGN: Modelling cost-effectiveness outcomes by separately adding three cessation interventions to standard cessation care offered to pregnant women in England. English National Health Service Stop Smoking Services (NHS SSS) statistics from 2019 to 2020 were used for estimating the base quit rate. Intervention effectiveness and cost data for interventions were taken from trial reports. Cost-effectiveness was derived using the economics of smoking in pregnancy (ESIP) model from a health service and personal social services perspective. Interventions were compared with each other as well as against standard cessation care. SETTING: English NHS SSS. PARTICIPANTS/CASES: A total of 13 799 pregnant women who accessed NHS SSS. Interventions and comparator; comparator: standard stop smoking support comprising behavioural intervention and an offer of nicotine replacement therapy (NRT). Three additive interventions were TMB, EB and CFIB. MEASUREMENTS: Incremental cost-effectiveness ratios per quality-adjusted life-years gained for both mothers and offspring over their life-times; return on investment (ROI); and cost-effectiveness acceptability curves (CEACs). FINDINGS: The addition of any of the interventions compared with standard care alone was preferred, but only significant for the addition of CFIB, with the CEAC suggesting an at least 90% chance of being favoured to standard care alone. When compared against each other CFIB appeared to yield the largest returns, but this was not significant. The estimated ROI for CFIB was £2 [95% confidence interval (CI) = £1-3] in health-care savings for every £1 spent by the NHS on the cessation intervention. CONCLUSIONS: For a health system which currently provides behavioural support and an offer of nicotine replacement therapy as standard stop smoking support for pregnant women, the greatest economic gains would be provided by operating an abstinent-contingent financial incentives scheme alongside this.

Clinical effectiveness and costs of pre-hospital inhaled methoxyflurane for acute pain in trauma in adults: non-randomised control group study.

AIMS: Inhaled methoxyflurane, newly licensed in Europe for acute trauma pain in adults, has limited evidence of effectiveness in the pre-hospital setting. We aimed to investigate the clinical effectiveness and costs of methoxyflurane delivered when administered by ambulance staff compared with usual analgesic practice (UAP) for adults with trauma. METHODS: A non-randomised control group design was used to compare methoxyflurane versus Entonox® or parenteral analgesics. Verbal numerical pain scores (VNPS) were gathered over time in adults with moderate to severe trauma pain attended by ambulance staff trained in administering and supplied with methoxyflurane. Comparator VNPS were obtained from database records of UAP in similar patients. Clinical efficacy was tested using an Ordered Probit panel regression model of pain intensity linked by observational rules to VNPS. Scenario analyses were used to compare durations under analgesia spent in severe pain, and costs. RESULTS: Over the 12-month evaluation period, 96 trained paramedics and technicians prepared 510 doses of methoxyflurane for administration to a grand total of 483 patients. Thirty-two patients reported side effects, 19 of whom discontinued early. Thirteen patients, 10 aged over 75 years, were nonadherent to instructions given on inhaler use. Modelling results included demonstration of statistically significant clinical effectiveness of methoxyflurane over each comparator (all p-values <0.001). Methoxyflurane's time to achieve maximum pain relief was significantly faster (all p-values <0.001): 25.7 mins (95%CI 24.4-27.0) versus Entonox® 44.4 (39.5-49.3); 25.8 (24.5-27.1) versus IV paracetamol 40.7 (34.6-46.9); 25.7 (24.4-27.0) versus IV morphine sulfate 41.9 (38.9-44.8). Scenario analyses of time spent in severe pain (VNPS on administration just scoring 10 reducing to a score of 7) were significantly less for methoxyflurane (all difference p-values <0.001): 7.6 mins (95%CI 6.5-8.7) versus Entonox® 24.6 (20.1-29.0); 6.7 (5.6-7.7) versus IV paracetamol 23.0 (17.9-28.0); 6.9 (5.9-7.9) versus IV morphine sulfate 14.9 (13.3-16.6). Costing scenarios compared single-dose use of methoxyflurane versus Entonox® and versus parenteral analgesics (80-20% weighted episode mix of morphine sulfate and paracetamol). In both scenarios, the benefits of methoxyflurane were achieved at higher cost: the additional cost per treated patient was £8.77 versus Entonox® and £9.69 versus parenteral analgesics. The BNF list price for one vial containing a 3 mL dose of methoxyflurane for vaporisation in a Penthrox® inhaler is £17.89 per pack. CONCLUSION: Methoxyflurane administered by ambulance clinicians reduced moderate or severe pain due to trauma in adults more rapidly compared to Entonox® or parenteral drugs. Methoxyflurane provides a useful addition to pre-hospital analgesia.

A dynamic, modifiable model for estimating cost-effectiveness of smoking cessation interventions in pregnancy: application to an RCT of self-help delivered by text message.

BACKGROUND AND AIMS: Previous evaluations of smoking cessation interventions in pregnancy have several limitations. Our solution to these limitations is the Economics of Smoking in Pregnancy (ESIP) model, which estimates the life-time cost-effectiveness of smoking cessation interventions in pregnancy from a National Health Service (NHS) and personal social services perspective. We aim to (1) describe how ESIP has been constructed and (2) illustrate its use with trial data. METHODS: ESIP links mothers' and offspring pregnancy outcomes to estimate the burdens of smoking-related disease they experience with different rates of smoking in pregnancy, both in pregnancy and throughout their life-times. Smoking rates are inputted by model users. ESIP then estimates the costs of treating disease burdens and also mothers' and offspring life-years and quality-adjusted life years (QALYs). By comparing costs incurred and healthy life following different smoking rates, ESIP estimates incremental cost-effectiveness and benefit-cost ratios for mothers or offspring or both combined. We illustrate ESIP use using data from a pragmatic randomized controlled trial that tested a smoking cessation intervention in pregnancy. RESULTS: Throughout women's and offspring life-times, the intervention proved cheaper than usual care, having a negative incremental cost of £38.37 (interquartile range = £21.46-56.96) and it improved health, demonstrating a 0.04 increase in incremental QALYs for mothers and offspring, implying that it is 'dominant' over usual care. Benefit-cost ratios suggested that every £1 spent would generate a median of £14 (interquartile range = £8-20) in health-care savings. CONCLUSIONS: Economics of Smoking in Pregnancy is the first economic model to link mothers' and infants' costs and benefits while reporting cost-effectiveness in readily-comparable units. Using ESIP with data from a trial which reported only short-term economic analysis showed that the intervention was very likely to be cost-effective in the longer term and to generate health-care savings.

Assessment of the feasibility and clinical value of further research to evaluate the management options for children with Down syndrome and otitis media with effusion: a feasibility study.

BACKGROUND: There is clinical uncertainty of the benefits and costs of different treatment options for children with Down syndrome who have glue ear. This study was designed to assess the extent of this lack of knowledge and determine if pursuing further information would be practical, beneficial and cost-effective. OBJECTIVES: To assess the level and practical effect of current uncertainty around treatment options for children with Down syndrome and glue ear. To assess the feasibility of studying the options for management of glue ear in children with Down syndrome via a randomised controlled trial (RCT) or multicentre prospective cohort study by evaluating the willingness of (1) parents to agree to randomisation for their children and (2) clinicians to recruit participants to a definitive study. To undertake value of information analyses to demonstrate the potential economic benefit from undertaking further research. DESIGN: A feasibility study exploring the views of parents of children with Down syndrome and professionals who have responsibility for the health and education of children with Down syndrome, on the participation in, and value of, future research into interventions for glue ear. Data were collected from parents via self-completed questionnaires, face-to-face interviews and focus groups and from professionals via online questionnaires and a Delphi review exercise. Development of economic models to represent clinical pathways of care and a RCT informed a value of information (VOI) analysis. SETTING: UK (professionals); East Midlands region of the UK (parents). PARTICIPANTS: Parents of children aged 1-11 years with Down syndrome (n = 156). Professionals including audiologists, ear, nose and throat surgeons, audiological physicians, speech and language therapists, and teachers of the deaf (n = 128). MAIN OUTCOME MEASURES: Quantitative and qualitative data on parental views and experiences of glue ear and its effects; interventions and treatment received; taking part in research and factors that would encourage or discourage participation; and the importance of various outcome domains to them and for their children. For professionals: information on caseloads; approaches to clinical management; opinions on frequency and significance of the consequences of glue ear for this population; importance of different outcome measures; opinions of interventions and their role in future research; views on health research; facilitators and barriers to recruitment, and participation in research involving RCTs. RESULTS: The complexity of the experience and individual characteristics of children with Down syndrome poses challenges for the design of any future research but these challenges were not considered by professionals to raise sufficient barriers to prevent it being undertaken. Parents were generally supportive of the need for, and value of, research but identified practical and emotional issues that would need addressing. Glue ear was considered to impact more on speech, language and communication than on hearing. Outcome measures for future research would need to evaluate these elements but measures should be designed specifically for the population. Parents and professionals identified randomisation as a significant barrier to participation. The VOI analyses identified lack of data as problematic but concluded that a future trial involving surgical intervention would be feasible at costs of < £650,000. CONCLUSIONS: Future research into the benefits of interventions for glue ear in children with Down syndrome would be feasible and could be cost-effective but should be carefully designed to facilitate and maximise participation from parents and professionals responsible for recruitment. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Demographic and past screening behaviors of men attending a free community screening program for prostate cancer.

This study characterizes demographic and past prostate screening behaviors of men who participated in a free screening for prostate cancer. Demographics, past prostate screening behavior, perceived risk, and cancer worry were assessed in 1,680 men. Mean age was 58.2 years, 56% were White, and 76% had health insurance. Men with insurance were more likely to have had a previous prostate-specific antigen (PSA) test and digital rectal exam (DRE). White men were more likely to have had a previous PSA and DRE and to have discussed PSA testing with a physician than African American men. African American men reported greater perceived risk and more worry than White men. Screening differences between African American and White men were explained by insurance status. These results may help guide the development of and promotion for future screening programs. Future efforts should be directed at increasing awareness about screening procedures for prostate cancer.

In vivo and in vitro assessment of the androgenic potential of a pulp and paper mill effluent.

The androgenic potential of a New Zealand pulp and paper mill effluent was measured by applying a combination of in vitro and in vivo bioassays with mosquitofish (Gambusia affinis) and goldfish (Carassius auratus). The in vivo method assessed the rate of gonopodial development (masculinization) and alterations from normal reproductive behavior in adult female mosquitofish exposed for 21 d to untreated or secondary-treated pulp mill effluent. A second in vivo mosquitofish exposure tested the effect of glass-fiber (type C) filtration of secondary-treated effluent on rates of expression of the same endpoints. Extractable organics analyses of effluents and extracts thereof were conducted. Mosquitofish demonstrated significant masculinization on exposure to either treated or untreated effluent; the frequency of gonopodial development was reduced with effluent secondary-treatment. Male mating behavior was observed in the masculinized adult females. Glass-fiber (type F) filtration of the treated effluent eliminated the masculinizing effect, suggesting that the bioactive compounds were associated with the suspended solids. The in vitro method measured the binding of compounds within a treated thermomechanical/bleached kraft effluent extract to androgen receptors contained in goldfish testis cytosol. Exposure to extracts of either the particulate (glass-fiber filtered) or the dissolved organic fraction of the effluent produced significant binding (as indicated by the displacement of radiolabeled testosterone) to the androgen receptor in goldfish gonadal tissue. Thus, the dissolved organics extract of the treated effluent contained compounds androgenic to goldfish in vitro but not to mosquitofish in vivo. The combined in vitro and in vivo data suggest that the effluent in question could exert effects on the reproductive physiology of fishes through an androgenic mechanism. The androgenic compounds androstenedione and testosterone were not detected in the extracts used for the in vitro component of this study.