Fairer decisions, better health for all : Health equity and cost-effectiveness analysis

This report provides a non-technical introduction to practical methods for using cost-effectiveness analysis to address health equity concerns, with applications to low-, middle- and high-income countries. These methods can provide information about the likely impacts of alternative health policy decisions on inequalities in health, financial risk protection and other health-related outcomes that may be considered unfair, allowing for the distribution of costs as well as benefits. They can also provide information about the trade-offs that sometimes arise between improving total health and reducing health inequalities of different kinds. We distinguish three general ways of using cost-effectiveness analysis to address health equity concerns: (1) equity impact analysis, which quantifies the distribution of costs and effects across a population by equity-relevant variables such as socioeconomic status, ethnicity, location, gender, age and severity of illness; (2) equity constraint analysis, which counts the cost of choosing fairer but less cost-effective options; and (3) equity weighting analysis, which uses equity weights or parameters to explore how much concern for equity is required to choose fairer but less cost-effective options. We hope this report will raise awareness of the practical tools of cost-effectiveness analysis that are now available to help give health care and public health policy makers a better understanding of who gains and who loses from their priority setting decisions

Aortic haemodynamics: the effects of habitual endurance exercise, age and muscle sympathetic vasomotor outflow in healthy men

PURPOSE: We determined the effect of habitual endurance exercise and age on aortic pulse wave velocity (aPWV), augmentation pressure (AP) and systolic blood pressure (aSBP), with statistical adjustments of aPWV and AP for heart rate and aortic mean arterial pressure, when appropriate. Furthermore, we assessed whether muscle sympathetic nerve activity (MSNA) correlates with AP in young and middle-aged men. METHODS: Aortic PWV, AP, aortic blood pressure (applanation tonometry; SphygmoCor) and MSNA (peroneal microneurography) were recorded in 46 normotensive men who were either young or middle-aged and endurance-trained runners or recreationally active nonrunners (10 nonrunners and 13 runners within each age-group). Between-group differences and relationships between variables were assessed via ANOVA/ANCOVA and Pearson product-moment correlation coefficients, respectively. RESULTS: Adjusted aPWV and adjusted AP were similar between runners and nonrunners in both age groups (all, P > 0.05), but higher with age (all, P < 0.001), with a greater effect size for the age-related difference in AP in runners (Hedges’ g, 3.6 vs 2.6). aSBP was lower in young (P = 0.009; g = 2.6), but not middle-aged (P = 0.341; g = 1.1), runners compared to nonrunners. MSNA burst frequency did not correlate with AP in either age group (young: r = 0.00, P = 0.994; middle-aged: r = − 0.11, P = 0.604). CONCLUSION: There is an age-dependent effect of habitual exercise on aortic haemodynamics, with lower aSBP in young runners compared to nonrunners only. Statistical adjustment of aPWV and AP markedly influenced the outcomes of this study, highlighting the importance of performing these analyses. Further, peripheral sympathetic vasomotor outflow and AP were not correlated in young or middle-aged normotensive men

The influence of habitual endurance exercise on carotid artery strain and strain-rate in young and middle-aged men

Central arterial stiffness is an independent predictor of cardiovascular risk that can be modified by exercise training. However, conventional local measures of carotid artery stiffness display conflicting responses to habitual endurance exercise in young and older adults. 2D-Strain imaging of the common carotid artery (CCA) quantifies circumferential deformation (strain) of the arterial wall across the cardiac cycle, which is more sensitive at detecting age-related alterations in CCA stiffness than conventional methods. Therefore, the study was designed to examine the relationship between habitual endurance exercise (running) and CCA 2D-Strain parameters in young and middle-aged men. Short-axis ultrasound images of the CCA were obtained from 13 young nonrunners (23 years [95% CI: 21-26]), 19 young runners (24 [22-26]), 13 middle-aged nonrunners (54 [52-56]) and 19 middle-aged runners (56 [54-58]). Images were analysed for peak circumferential strain (PCS; magnitude of deformation) as well as systolic and diastolic strain-rate (S-SR and D-SR; deformation velocity) and group differences were examined via two-way ANOVA. PCS, S-SR and D-SR were attenuated in middle-aged males when compared to young men (all P ≤ 0.001). PCS and S-SR were elevated in young and middle-aged runners when compared to nonrunners (P = 0.002 and P =0.009 respectively), but no age*training status interaction was observed. In contrast, there was no influence of habitual running on D-SR. Habitual exercise is associated with comparable improvements in CCA 2D-Strain parameters in young and middle-aged men, but the age-related decline in PCS and S-SR may be more amenable to habitual endurance exercise than D-SR

The influence of barosensory vessel mechanics on the vascular sympathetic baroreflex: Insights into ageing and blood pressure homeostasis

Changes in the arterial baroreflex arc contribute to elevated sympathetic outflow and altered reflex control of blood pressure with human ageing. Utilizing ultrasound and sympathetic microneurography (muscle sympathetic nerve activity; MSNA) we investigated the relationships between aortic and carotid artery wall tension (indices of baroreceptor activation) and the vascular sympathetic baroreflex operating point (OP; MSNA burst incidence) in healthy, normotensive young (n = 27, 23 ± 3 years) and middle-aged men (n = 22, 55 ± 4 years). In young men, the OP was positively related to the magnitude and rate of unloading and time spent unloaded in the aortic artery (r = 0.56, 0.65 and 0.51, P = 0.02, 0.003 and 0.03), but not related to the magnitude or rate of unloading or time spent unloaded in the carotid artery (r = -0.32, -0.07 and 0.06, P = 0.25, 0.81 and 0.85). In contrast, in middle-aged men, the OP was not related to either the magnitude or rate of unloading or time spent unloaded in the aortic (r = 0.22, 0.21 and 0.27, P = 0.41, 0.43 and 031) or carotid artery (r = 0.48, 0.28 and -0.01, P = 0.06, 0.25 and 0.98). In conclusion, in young men, aortic unloading mechanics may play a role in determining the vascular sympathetic baroreflex OP. In contrast, in middle-aged men, barosensory vessel unloading mechanics do not appear to determine the vascular sympathetic baroreflex OP, and therefore do not contribute to age-related arterial baroreflex resetting and increased resting MSNA. KEYWORDS: muscle sympathetic nerve activity; barosensory vessel unloading mechanics; healthy ageing; sympathetic nervous system; baroreflex Page Break NEW AND NOTEWORTHY We assessed the influence of barosensory vessel mechanics (magnitude and rate of unloading and time spent unloaded) as a surrogate for baroreceptor unloading. In young men, aortic unloading mechanics are important in regulating the operating point of the vascular sympathetic baroreflex, whereas in middle-aged men, these arterial mechanics do not influence this operating point. The age-related increase in resting muscle sympathetic nerve activity does not appear to be driven by altered baroreceptor input from stiffer barosensory vessels

Stimulus-specific functional remodeling of the left ventricle in endurance and resistance-trained men

Left ventricular (LV) structural remodeling following athletic training has been evidenced through training-specific changes in wall thickness and geometry. Whether the LV response to changes in hemodynamic load also adapts in a training-specific manner is unknown. Using echocardiography, we examined LV responses of endurance-trained (n = 15), resistance-trained (n = 14), and nonathletic men (n = 13) to 1) 20, 40, and 60% one repetition-maximum (1RM), leg-press exercise and 2) intravascular Gelofusine infusion (7 mL/kg) with passive leg raise. While resting heart rate was lower in endurance-trained participants versus controls (P = 0.001), blood pressure was similar between groups. Endurance-trained individuals had lower wall thickness but greater LV mass relative to body surface area versus controls, with no difference between resistance-trained individuals and controls. Leg press evoked a similar increase in blood pressure; however, resistance-trained participants preserved stroke volume (SV; −3 ± 8%) versus controls at 60% 1RM (−15 ± 7%, P = 0.001). While the maintenance of SV was related to the change in longitudinal strain across all groups (R = 0.537; P = 0.007), time-to-peak strain was maintained in resistance-trained but delayed in endurance-trained individuals (1 vs. 12% delay; P = 0.021). Volume infusion caused a similar increase in end-diastolic volume (EDV) and SV across groups, but leg raise further increased EDV only in endurance-trained individuals (5 ± 5 to 8 ± 5%; P = 0.018). Correlation analysis revealed a relationship between SV and longitudinal strain following infusion and leg raise (R = 0.334, P = 0.054); however, we observed no between-group differences in longitudinal myocardial mechanics. In conclusion, resistance-trained individuals better maintained SV during pressure loading, whereas endurance-trained individuals demonstrated greater EDV reserve during volume loading. These data provide novel evidence of training-specific LV functional remodeling. NEW & NOTEWORTHY Training-specific functional remodeling of the LV in response to different loading conditions has been recently suggested, but not experimentally tested in the same group of individuals. Our data provide novel evidence of a dichotomous, training-specific LV adaptive response to hemodynamic pressure or volume loading

Upward resetting of the vascular sympathetic baroreflex in middle-aged male runners

This study focussed on the influence of habitual endurance exercise training (i.e. committed runner or non-runner) on the regulation of muscle sympathetic nerve activity (MSNA) and arterial pressure in middle-aged (50 to 63 years, n= 23) and younger (19 to 30 years; n=23) normotensive men. Haemodynamic and neurophysiological assessments were performed at rest. Indices of vascular sympathetic baroreflex function were determined from the relationship between spontaneous changes in diastolic blood pressure (DBP) and MSNA. Large vessel arterial stiffness and left ventricular stroke volume also were measured. Paired comparisons were performed within each age-category. Mean arterial pressure and basal MSNA bursts·min-1 were not different between age-matched runners and non-runners. However, MSNA bursts·100 heartbeats-1, an index of baroreflex regulation of MSNA (vascular sympathetic baroreflex operating point) was higher for middle-aged runners (P=0.006), whereas this was not different between young runners and non-runners. The slope of the DBP-MSNA relationship (vascular sympathetic baroreflex gain) was not different between groups in either age-category. Aortic pulse wave velocity was lower for runners of both age-categories (P<0.03), although carotid β stiffness was lower only for middle-aged runners (P=0.04). For runners of both age-categories, stroke volume was larger, while heart rate was lower (both P<0.01). In conclusion, we suggest that neural remodelling and upward setting of the vascular sympathetic baroreflex compensates for cardiovascular adaptations after many years committed to endurance exercise training, presumably to maintain arterial blood pressure stability

Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. METHODS: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. FINDINGS: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. INTERPRETATION: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. FUNDING: UK National Institute for Health Research

Using Cost-Effectiveness Analysis to Address Health Equity Concerns

This articles serves as a guide to using cost-effectiveness analysis (CEA) to address health equity concerns. We first introduce the "equity impact plane," a tool for considering trade-offs between improving total health-the objective underpinning conventional CEA-and equity objectives, such as reducing social inequality in health or prioritizing the severely ill. Improving total health may clash with reducing social inequality in health, for example, when effective delivery of services to disadvantaged communities requires additional costs. Who gains and who loses from a cost-increasing health program depends on differences among people in terms of health risks, uptake, quality, adherence, capacity to benefit, and-crucially-who bears the opportunity costs of diverting scarce resources from other uses. We describe two main ways of using CEA to address health equity concerns: 1) equity impact analysis, which quantifies the distribution of costs and effects by equity-relevant variables, such as socioeconomic status, location, ethnicity, sex, and severity of illness; and 2) equity trade-off analysis, which quantifies trade-offs between improving total health and other equity objectives. One way to analyze equity trade-offs is to count the cost of fairer but less cost-effective options in terms of health forgone. Another method is to explore how much concern for equity is required to choose fairer but less cost-effective options using equity weights or parameters. We hope this article will help the health technology assessment community navigate the practical options now available for conducting equity-informative CEA that gives policymakers a better understanding of equity impacts and trade-offs

Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial

INTRODUCTION: Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell transplant. Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life. METHODS AND ANALYSIS: Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a national, phase III, multicentre, randomised controlled trial comparing standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide to lenalidomide+ixazomib, in patients with newly diagnosed multiple myeloma not suitable for stem cell transplant. Overall, 740 participants will be registered into the trial to allow 720 and 478 to be randomised at induction and maintenance, respectively.All participants will receive IRD induction with the dosing strategy randomised (1:1) at trial entry. Patients randomised to the standard, reactive arm will commence at the full dose followed by toxicity dependent reactive modifications. Patients randomised to the adaptive arm will commence at a dose level determined by their International Myeloma Working Group frailty score. Following 12 cycles of induction treatment, participants alive and progression free will undergo a second (double-blind) randomisation on a 1:1 basis to maintenance treatment with lenalidomide+placebo versus lenalidomide+ixazomib until disease progression or intolerance. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North East-Tyne & Wear South Research Ethics Committee (19/NE/0125) and capacity and capability confirmed by local research and development departments for each participating centre prior to opening to recruitment. Participants are required to provide written informed consent prior to trial registration. Trial results will be disseminated by conference presentations and peer-reviewed publications