Julian Nam

Fractional flow reserve vs. angiography in guiding management to optimize outcomes in non-ST-segment elevation myocardial infarction: the British Heart Foundation FAMOUS–NSTEMI randomized trial

Aim We assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care. Methods and results We conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (−0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups. Conclusion In NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness.

Close contact casting vs surgery for initial treatment of unstable ankle fractures in older adults: A randomized clinical trial

Importance Ankle fractures cause substantial morbidity in older persons. Surgical fixation is the contemporary intervention but is associated with infection and other healing complications. Objective To determine whether initial fracture treatment with close contact casting, a molded below-knee cast with minimal padding, offers outcome equivalent to that with immediate surgery, with fewer complications and less health resource use. Design, Setting, and Participants This was a pragmatic, equivalence, randomized clinical trial with blinded outcome assessors. A pilot study commenced in May 2004, followed by multicenter recruitment from July 2010 to November 2013; follow-up was completed May 2014. Recruitment was from 24 UK major trauma centers and general hospitals. Participants were 620 adults older than 60 years with acute, overtly unstable ankle fracture. Exclusions were serious limb or concomitant disease or substantial cognitive impairment. Interventions Participants were randomly assigned to surgery (n = 309) or casting (n = 311). Casts were applied in the operating room under general or spinal anesthesia by a trained surgeon. Main Outcomes and Measures The primary 6-month, per-protocol outcome was the Olerud-Molander Ankle Score at 6 months (OMAS; range, 0-100; higher scores indicate better outcomes and fewer symptoms), equivalence prespecified as ±6 points. Secondary outcomes were quality of life, pain, ankle motion, mobility, complications, health resource use, and patient satisfaction. Results Among 620 adults (mean age, 71 years; 460 [74%] women) who were randomized, 593 (96%) completed the study. Nearly all participants (579/620; 93%) received allocated treatment; 52 of 275 (19%) who initially received casting later converted to surgery, which was allowable in the casting treatment pathway to manage early loss of fracture reduction. At 6 months, casting resulted in ankle function equivalent to that with surgery (OMAS score, 66.0 [95% CI, 63.6-68.5] for surgery vs 64.5 [95% CI, 61.8-67.2] for casting; mean difference, -0.6 [95% CI, -3.9 to 2.6]; P for equivalence = .001). Infection and wound breakdown were more common with surgery (29/298 [10%] vs 4/275 [1%]; odds ratio [OR], 7.3 [95% CI, 2.6-20.2]), as were additional operating room procedures (18/298 [6%] for surgery and 3/275 [1%] for casting; OR, 5.8 [95% CI, 1.8-18.7]). Radiologic malunion was more common in the casting group (38/249 [15%] vs 8/274 [3%] for surgery; OR, 6.0 [95% CI, 2.8-12.9]). Casting required less operating room time compared with surgery (mean difference [minutes/participant], -54 [95% CI, -58 to -50]). There were no significant differences in other secondary outcomes: quality of life, pain, ankle motion, mobility, and patient satisfaction. Conclusions and Relevance Among older adults with unstable ankle fracture, the use of close contact casting compared with surgery resulted in similar functional outcomes at 6 months. Close contact casting may be an appropriate treatment for such patients. Trial Registration isrctn.com Identifier: ISRCTN04180738.

Bayesian Solutions for Handling Uncertainty in Survival Extrapolation

Objective. Survival extrapolation using a single, best-fit model ignores 2 sources of model uncertainty: uncertainty in the true underlying distribution and uncertainty about the stability of the model parameters over time. Bayesian model averaging (BMA) has been used to account for the former, but it can also account for the latter. We investigated BMA using a published comparison of the Charnley and Spectron hip prostheses using the original 8-year follow-up registry data. Methods. A wide variety of alternative distributions were fitted. Two additional distributions were used to address uncertainty about parameter stability: optimistic and skeptical. The optimistic (skeptical) model represented the model distribution with the highest (lowest) estimated probabilities of survival but reestimated using, as prior information, the most optimistic (skeptical) parameter estimated for intermediate follow-up periods. Distributions were then averaged assuming the same posterior probabilities for the optimistic, skeptical, and noninformative models. Cost-effectiveness was compared using both the original 8-year and extended 16-year follow-up data. Results. We found that all models obtained similar revision-free years during the observed period. In contrast, there was variability over the decision time horizon. Over the observed period, we detected considerable uncertainty in the shape parameter for Spectron. After BMA, Spectron was cost-effective at a threshold of £20,000 with 93% probability, whereas the best-fit model was 100%; by contrast, with a 16-year follow-up, it was 0%. Conclusions. This case study casts doubt on the ability of the single best-fit model selected by information criteria statistics to adequately capture model uncertainty. Under this scenario, BMA weighted by posterior probabilities better addressed model uncertainty. However, there is still value in regularly updating health economic models, even where decision uncertainty is low.

OP86 Evaluating Health in Pregnancy grants in Scotland: a natural experiment

Background The developmental model of the origins of chronic diseases has shown the importance of undernutrition and poor development in utero on disease in later life, including coronary heart disease and stroke. Tracing disease back to fetal development means that this period can also be seen as the origin of health inequalities and, as such, a priority time for intervention to improve health outcomes. This paper reports on the evaluation of Health in Pregnancy (HiP) grants, a UK-wide unconditional universal cash transfer of £190 made to pregnant women who had sought medical advice before the 25th week of pregnancy. The grant was designed to provide additional financial support towards a healthy lifestyle including diet, with the cash element providing a greater incentive to seek advice at the appropriate time. Methods This natural experiment was evaluated using routinely collected data for all singleton births in Scotland before (2004–2009), during (2009–2011) and after (2011–2013) the introduction of the HiP grants. In addition to the primary outcome of birthweight (BW) we evaluated the effect on other measures of stage and size and maternal behaviour including contacting the midwife before 25 weeks. We looked for evidence of differential effects among subgroups including those defined by area deprivation, social class, marital status and maternal diabetes. The analysis was restricted to Scotland because of the high quality routine data available. We used interrupted time series models adjusted for time trends and seasonality in addition to maternal and birth characteristics to estimate the effect of the intervention (INT) and post-intervention (POST) periods relative to the years pre-intervention, and used multiple imputation to reduce any bias due to missing data. Results Among the 525,400 singleton births from 2004–2013 there was no significant relationship with BW (INT = −2.3 g, 95% CI: −1.9 to 6.6) or other measures of size and stage. The intervention was associated with an increase in the odds of booking before 25 weeks that disappeared post-intervention (INT OR = 1.10, 95% CI: 1.02 to 1.18; POST OR = 0.91, 95% CI: 0.83–1.00). Results for the subgroups largely mirrored those seen for the population. Conclusion The small financial incentive did not have an impact on birthweight or other measures of size or stage but did appear to have changed health seeking behaviour. It is not clear that a threshold of 25 weeks is optimal to improve birth outcomes given that this is late in the pregnancy. Future evaluations would be enhanced if some randomisation were included in the study design.

FRACTIONAL FLOW RESERVE (FFR) VERSUS ANGIOGRAPHY IN GUIDING MANAGEMENT TO OPTIMIZE OUTCOMES IN NON-ST ELEVATION MYOCARDIAL INFARCTION (FAMOUS - NSTEMI) HEALTH ECONOMIC ANALYSIS

An economic model was developed to compare the medical resource cost and health outcome effects of physiology-guided management with FFR compared with standard angiography-guided management in patients with non-ST elevation myocardial infarction based on participants British Heart Foundation FAMOUS-