The impact of cardiovascular disease (CVD) comorbidity on resection rates and survival for patients with early-stage non-small-cell lung cancer (NSCLC) is unclear. We explored if CVD comorbidity ...explained surgical resection rate variation and the impact on survival if resection rates increased.
Cancer registry data consisted of English patients diagnosed with NSCLC from 2012 to 2016. Linked hospital records identified CVD comorbidities. We investigated resection rate variation by geographical region using funnel plots; resection and death rates using time-to-event analysis. We modelled an increased propensity for resection in regions with the lowest resection rates and estimated survival change.
Among 57,373 patients with Stage 1-3A NSCLC, resection rates varied considerably between regions. Patients with CVD comorbidity had lower resection rates and higher mortality rates. CVD comorbidity explained only 1.9% of the variation in resection rates. For every 100 CVD comorbid patients, increasing resection in regions with the lowest rates from 24 to 44% would result in 16 more patients resected and alive after 1 year and two fewer deaths overall.
Variation in regional resection rate is not explained by CVD comorbidities. Increasing resection in patients with CVD comorbidity to the levels of the highest resecting region would increase 1-year survival.
Objectives To evaluate whether either angiotensin converting enzyme (ACE) inhibitors or other classes of antihypertensive drug attenuate or increase growth rates of small infrarenal abdominal aortic ...aneurysms. Methods Prospective cohort study of 1701 patients enrolled in the UK Small Aneurysm Trial or associated study at 93 hospitals between 1991 and 1995 and who had at least two ultrasound measurements of aneurysm diameter and baseline drug prescription data recorded. Abdominal aortic aneurysm diameter was measured in the anterior-posterior plane using ultrasound. The mean growth rate was estimated through a mixed-effects linear growth model. Results Mean aneurysm growth rate in 169 patients taking ACE inhibitors at baseline was 3.33 mm/y vs 2.77 mm/y in the remaining 1532 patients, P = .009. The significance of this finding did not alter after adjustment for known confounders. The prescription of any antihypertensive agent and other specific classes of antihypertensive drugs were not found to be associated with aneurysm growth rate. Conclusion These results show that patients taking ACE inhibitors have faster aneurysm growth and are in conflict with the observation from a large Canadian data-base that aneurysm patients taking ACE inhibitors are less likely to present with aneurysm rupture. There is an urgent need for a randomized trial to assess whether ACE inhibitors are beneficial or harmful to patients with aneurysms below the threshold size for surgical intervention.
To investigate the safety and cost-effectiveness of lengthening the time between surveillance ultrasound scans in the UK Abdominal Aortic Aneurysm (AAA) Screening Programme.
A discrete event ...simulation model was used to evaluate the cost-effectiveness of AAA screening for men aged 65, comparing current surveillance intervals to 6 alternative surveillance interval strategies that lengthened the time between surveillance scans for 1 or more AAA size categories. The model considered clinical events and costs incurred over a 30-year time horizon and the cost per quality-adjusted life year (QALY). The model adopted the National Health Service perspective and discounted future costs and benefits at 3.5%.
Compared with current practice, alternative surveillance strategies resulted in up to a 4% reduction in the number of elective AAA repairs but with an increase of up to 1.6% in the number of AAA ruptures and AAA-related deaths. Alternative strategies resulted in a small reduction in QALYs compared to current practice but with reduced costs. Two strategies that lengthened surveillance intervals in only very small AAAs (3.0-3.9 cm) provided, at a cost-effectiveness threshold of £20 000 per QALY, the highest positive incremental net benefit. There was negligible chance that current practice is the most cost-effective strategy at any threshold below £40 000 per QALY.
Lengthening surveillance intervals in the UK Abdominal Aortic Aneurysm Screening Programme, especially for small AAA, can marginally reduce the incremental cost per QALY of the program. Nevertheless, whether the cost savings from refining surveillance strategies justifies a change in clinical practice is unclear.
•The National Health Service Abdominal Aortic Aneurysm Screening Programme has been shown to be highly cost-effective. Recently, the prevalence of screen-detected abdominal aortic aneurysm (AAA) has fallen. If this trend continues, the cost-effectiveness of AAA screening is threatened. One option to improve program cost-effectiveness is to extend the length of time between surveillance scans for men who are found to have AAA at screening. The potential safety and cost savings associated with such a change are unknown.•Extending the length of time between surveillance scans for men with screen-detected AAA in the Abdominal Aortic Aneurysm Screening Programme, especially for those with smaller AAAs, reduces the incremental cost per quality-adjusted life-year of the program. This is associated with a small increase in the number of adverse clinical events in the overall population of men invited for screening.•It is unclear whether the benefit of cost saving from refining surveillance strategies justifies the increased harms associated with such a change in clinical practice. Furthermore, realizing the benefits of minimized surveillance strategies for individual screening units may be difficult owing to the regional structure of the AAA screening workforce.
This paper presents the R package bcrm for conducting and assessing Bayesian continual reassessment method (CRM) designs in Phase I dose-escalation trials. CRM designsare a class of adaptive design ...that select the dose to be given to the next recruited patient based on accumulating toxicity data from patients already recruited into the trial, often using Bayesian methodology. Despite the original CRM design being proposed in 1990, the methodology is still not widely implemented within oncology Phase I trials. The aim of this paper is to demonstrate, through example of the bcrm package, how a variety of possible designs can be easily implemented within the R statistical software, and how properties of the designs can be communicated to trial investigators using simple textual and graphical output obtained from the package. This in turn should facilitate an iterative process to allow a design to be chosen that is suitable to the needs of the investigator. Our bcrm package is the first to offer a large comprehensive choice of CRM designs, priors and escalation procedures, which can be easily compared and contrasted within the package through the assessment of operating characteristics.
Ruptured abdominal aortic aneurysm (AAA) is a common vascular emergency. The mortality from emergency endovascular repair may be much lower than the 40-50% reported for open surgery.
To assess ...whether or not a strategy of endovascular repair compared with open repair reduces 30-day and mid-term mortality (including costs and cost-effectiveness) among patients with a suspected ruptured AAA.
Randomised controlled trial, with computer-generated telephone randomisation of participants in a 1 : 1 ratio, using variable block size, stratified by centre and without blinding.
Vascular centres in the UK (
= 29) and Canada (
= 1) between 2009 and 2013.
A total of 613 eligible participants (480 men) with a ruptured aneurysm, clinically diagnosed at the trial centre.
A total of 316 participants were randomised to the endovascular strategy group (immediate computerised tomography followed by endovascular repair if anatomically suitable or, if not suitable, open repair) and 297 were randomised to the open repair group (computerised tomography optional).
The primary outcome measure was 30-day mortality, with 30-day reinterventions, costs and disposal as early secondary outcome measures. Later outcome measures included 1- and 3-year mortality, reinterventions, quality of life (QoL) and cost-effectiveness.
The 30-day mortality was 35.4% in the endovascular strategy group and 37.4% in the open repair group odds ratio (OR) 0.92, 95% confidence interval (CI) 0.66 to 1.28;
= 0.62, and, after adjustment for age, sex and Hardman index, OR 0.94, 95% CI 0.67 to 1.33. The endovascular strategy appeared to be more effective in women than in men (interaction test
= 0.02). More discharges in the endovascular strategy group (94%) than in the open repair group (77%) were directly to home (
< 0.001). Average 30-day costs were similar between groups, with the mean difference in costs being -£1186 (95% CI -£2997 to £625), favouring the endovascular strategy group. After 1 year, survival and reintervention rates were similar in the two groups, QoL (at both 3 and 12 months) was higher in the endovascular strategy group and the mean cost difference was -£2329 (95% CI -£5489 to £922). At 3 years, mortality was 48% and 56% in the endovascular strategy group and open repair group, respectively (OR 0.73, 95% CI 0.53 to 1.00;
= 0.053), with a stronger benefit for the endovascular strategy in the subgroup of 502 participants in whom repair was started for a proven rupture (OR 0.62, 95% CI 0.43 to 0.89;
= 0.009), whereas aneurysm-related reintervention rates were non-significantly higher in this group. At 3 years, considering all participants, there was a mean difference of 0.174 quality-adjusted life-years (QALYs) (95% CI 0.002 to 0.353 QALYs) and, among the endovascular strategy group, a cost difference of -£2605 (95% CI -£5966 to £702), leading to 88% of estimates in the cost-effectiveness plane being in the quadrant showing the endovascular strategy to be 'dominant'.
Because of the pragmatic design of this trial, 33 participants in the endovascular strategy group and 26 in the open repair group breached randomisation allocation.
The endovascular strategy was not associated with a significant reduction in either 30-day mortality or cost but was associated with faster participant recovery. By 3 years, the endovascular strategy showed a survival and QALY gain and was highly likely to be cost-effective. Future research could include improving resuscitation for older persons with circulatory collapse, the impact of local anaesthesia and emergency consent procedures.
Current Controlled Trials ISRCTN48334791 and NCT00746122.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 22, No. 31. See the NIHR Journals Library website for further project information.
Background
Deferrals due to low hemoglobin are time‐consuming and costly for blood donors and donation services. Furthermore, accepting donations from those with low hemoglobin could represent a ...significant safety issue. One approach to reduce them is to use hemoglobin concentration alongside donor characteristics to inform personalized inter‐donation intervals.
Study Design and Methods
We used data from 17,308 donors to inform a discrete event simulation model comparing personalized inter‐donation intervals using “post‐donation” testing (i.e., estimating current hemoglobin from that measured by a hematology analyzer at last donation) versus the current approach in England (i.e., pre‐donation testing with fixed intervals of 12‐weeks for men and 16‐weeks for women). We reported the impact on total donations, low hemoglobin deferrals, inappropriate bleeds, and blood service costs. Personalized inter‐donation intervals were defined using mixed‐effects modeling to estimate hemoglobin trajectories and probability of crossing hemoglobin donation thresholds.
Results
The model had generally good internal validation, with predicted events similar to those observed. Over 1 year, a personalized strategy requiring ≥90% probability of being over the hemoglobin threshold, minimized adverse events (low hemoglobin deferrals and inappropriate bleeds) in both sexes and costs in women. Donations per adverse event improved from 3.4 (95% uncertainty interval 2.8, 3.7) under the current strategy to 14.8 (11.6, 19.2) in women, and from 7.1 (6.1, 8.5) to 26.9 (20.8, 42.6) in men. In comparison, a strategy incorporating early returns for those with high certainty of being over the threshold maximized total donations in both men and women, but was less favorable in terms of adverse events, with 8.4 donations per adverse event in women (7.0, 10,1) and 14.8 (12.1, 21.0) in men.
Discussion
Personalized inter‐donation intervals using post‐donation testing combined with modeling of hemoglobin trajectories can help reduce deferrals, inappropriate bleeds, and costs.
Abdominal aortic aneurysm (AAA) screening programmes have been established for men in the UK to reduce deaths from AAA rupture. Whether or not screening should be extended to women is uncertain.
To ...evaluate the cost-effectiveness of population screening for AAAs in women and compare a range of screening options.
A discrete event simulation (DES) model was developed to provide a clinically realistic model of screening, surveillance, and elective and emergency AAA repair operations. Input parameters specifically for women were employed. The model was run for 10 million women, with parameter uncertainty addressed by probabilistic and deterministic sensitivity analyses.
Population screening in the UK.
Women aged ≥ 65 years, followed up to the age of 95 years.
Invitation to ultrasound screening, followed by surveillance for small AAAs and elective surgical repair for large AAAs.
Number of operations undertaken, AAA-related mortality, quality-adjusted life-years (QALYs), NHS costs and cost-effectiveness with annual discounting.
AAA surveillance data, National Vascular Registry, Hospital Episode Statistics, trials of elective and emergency AAA surgery, and the NHS Abdominal Aortic Aneurysm Screening Programme (NAAASP).
Systematic reviews of AAA prevalence and, for elective operations, suitability for endovascular aneurysm repair, non-intervention rates, operative mortality and literature reviews for other parameters.
The prevalence of AAAs (aortic diameter of ≥ 3.0 cm) was estimated as 0.43% in women aged 65 years and 1.15% at age 75 years. The corresponding attendance rates following invitation to screening were estimated as 73% and 62%, respectively. The base-case model adopted the same age at screening (65 years), definition of an AAA (diameter of ≥ 3.0 cm), surveillance intervals (1 year for AAAs with diameter of 3.0-4.4 cm, 3 months for AAAs with diameter of 4.5-5.4 cm) and AAA diameter for consideration of surgery (5.5 cm) as in NAAASP for men. Per woman invited to screening, the estimated gain in QALYs was 0.00110, and the incremental cost was £33.99. This gave an incremental cost-effectiveness ratio (ICER) of £31,000 per QALY gained. The corresponding incremental net monetary benefit at a threshold of £20,000 per QALY gained was -£12.03 (95% uncertainty interval -£27.88 to £22.12). Almost no sensitivity analyses brought the ICER below £20,000 per QALY gained; an exception was doubling the AAA prevalence to 0.86%, which resulted in an ICER of £13,000. Alternative screening options (increasing the screening age to 70 years, lowering the threshold for considering surgery to diameters of 5.0 cm or 4.5 cm, lowering the diameter defining an AAA in women to 2.5 cm and lengthening the surveillance intervals for the smallest AAAs) did not bring the ICER below £20,000 per QALY gained when considered either singly or in combination.
The model for women was not directly validated against empirical data. Some parameters were poorly estimated, potentially lacking relevance or unavailable for women.
The accepted criteria for a population-based AAA screening programme in women are not currently met.
A large-scale study is needed of the exact aortic size distribution for women screened at relevant ages. The DES model can be adapted to evaluate screening options in men.
This study is registered as PROSPERO CRD42015020444 and CRD42016043227.
The National Institute for Health Research Health Technology Assessment programme.
To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen ...adopted.
Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects meta-regression analysis.
In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95% CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I² = 19%). However, this naïve analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95% CI 0.17, 0.56), with no evidence of heterogeneity (I² = 0%). A meta-regression analysis was performed, which used the data available from the ten anti-D prophylaxis studies to inform us about the relative effectiveness of three licensed treatments. This gave an 83% probability that a dose of 1250 IU at 28 and 34 weeks is most effective and a 76% probability that a single dose of 1500 IU at 28-30 weeks is least effective.
There is strong evidence for the effectiveness of routine antenatal anti-D prophylaxis for prevention of sensitisation, in support of the policy of offering routine prophylaxis to all non-sensitised pregnant Rhesus negative women. All three licensed dose regimens are expected to be effective.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IntroductionAtrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but ...there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures.Methods and analysisSAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 2:1 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective.Ethics and disseminationThe London—Central Research Ethics Committee (19/LO/1597) and Confidentiality Advisory Group (19/CAG/0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee.Trial registration numberISRCTN72104369.
PDF
