Do Women Have a Higher Risk of Adverse Events after Carotid Revascularization?

Carotid artery stenosis is thought to cause up to 10% of ischemic strokes. Till now, the optimal treatment between carotid endarterectomy (CEA) and carotid artery stenting (CAS) remains debated, in particular for specific subgroups of patients. Available data suggest that female have higher risk of perioperative adverse events, but conflicting results comparing CEA and CAS regarding the benefit for male or female are present in the literature. A systematic review of recent publications on gender-related differences in operative risks is reported. Moreover, a consecutive cohort of 912 symptomatic and asymptomatic patients undergoing CEA (407, 44.6%) or CAS (505, 55.4%) in a single institution has been evaluated to determine the influence of gender (59.7% male vs. 40.3% female) on the outcomes after both revascularization procedures at 30 days and during 3 years of follow-up. Our experience seems to confirm literature data as regarding female higher risk of restenosis. Female patients had higher periprocedural (2.7% female vs. 0.9% male; p < 0.05) and long-term (11.4% female vs. 4.6% male; p < 0.05) restenosis rate. In conclusion, female anatomic and pathologic parameters should be taken into account for an accurate diagnosis of carotid stenosis and guidelines should be adjusted consequently

Church attendance and alloparenting: an analysis of fertility, social support and child development among English mothers

Many aspects of religious rituals suggest they provide adaptive benefits. Studies across societies consistently find that investments in ritual behaviour return high levels of cooperation. Another line of research finds that alloparental support to mothers increases maternal fertility and improves child outcomes. Although plausible, whether religious cooperation extends to alloparenting and/or affects child development remains unclear. Using 10 years of data collected from the Avon Longitudinal Study of Parents and Children (ALSPAC), we test the predictions that church attendance is positively associated with social support and fertility (n = 8207 to n = 8209), and that social support is positively associated with fertility and child development (n = 1766 to n = 6561). Results show that: (i) relative to not attending, church attendance is positively related to a woman's social network support and aid from co-religionists, (ii) aid from co-religionists is associated with increased family size, while (iii) fertility declines with extra-religious social network support. Moreover, while extra-religious social network support decreased over time, co-religionist aid remained constant. These findings suggest that religious and secular networks differ in their longevity and have divergent influences on a woman's fertility. We find some suggestive evidence that support to mothers and aid from co-religionists is positively associated with a child's cognitive ability at later stages of development. Findings provide mixed support for the premise that ritual, such as church attendance, is part of a strategy that returns high levels of support, fertility and improved child outcomes. Identifying the diversity and scope of cooperative breeding strategies across global religions presents an intriguing new horizon in the evolutionary study of religious systems. This article is part of the theme issue 'Ritual renaissance: new insights into the most human of behaviours'

Clinical Response to Procedural Stroke Following Carotid Endarterectomy:A Delphi Consensus Study

Objective: No dedicated studies have been performed on the optimal management of patients with an acute stroke related to carotid intervention nor is there a solid recommendation given in the European Society for Vascular Surgery guideline. By implementation of an international expert Delphi panel, this study aimed to obtain expert consensus on the optimal management of in hospital stroke occurring during or following CEA and to provide a practical treatment decision tree. Methods: A four round Delphi consensus study was performed including 31 experts. The aim of the first round was to investigate whether the conceptual model indicating the traditional division between intra- and post-procedural stroke in six phases was appropriate, and to identify relevant clinical responses during these six phases. In rounds 2, 3, and 4, the aim was to obtain consensus on the optimal response to stroke in each predefined setting. Consensus was reached in rounds 1, 3, and 4 when ≥ 70% of experts agreed on the preferred clinical response and in round 2 based on a Likert scale when a median of 7 – 9 (most adequate response) was given, IQR ≤ 2. Results: The experts agreed (> 80%) on the use of the conceptual model. Stroke laterality and type of anaesthesia were included in the treatment algorithm. Consensus was reached in 17 of 21 scenarios (> 80%). Perform diagnostics first for a contralateral stroke in any phase, and for an ipsilateral stroke during cross clamping, or apparent stroke after leaving the operation room. For an ipsilateral stroke during the wake up phase, no formal consensus was achieved, but 65% of the experts would perform diagnostics first. A CT brain combined with a CTA or duplex ultrasound of the carotid arteries should be performed. For an ipsilateral intra-operative stroke after flow restoration, the carotid artery should be re-explored immediately (75%). Conclusion: In patients having a stroke following carotid endarterectomy, expedited diagnostics should be performed initially in most phases. In patients who experience an ipsilateral intra-operative stroke following carotid clamp release, immediate re-exploration of the index carotid artery is recommended

Post-trial follow-up methodology in large randomised controlled trials: a systematic review.

BACKGROUND: Randomised controlled clinical trials typically have a relatively brief in-trial follow-up period which can underestimate safety signals and fail to detect long-term hazards, which may take years to appear. Extended follow-up after the scheduled closure of the trial allows detection of both persistent or enhanced beneficial effects following cessation of study treatment (i.e. a legacy effect) and the emergence of possible adverse effects (e.g. development of cancer). METHODS: A systematic review was conducted following PRISMA guidelines to qualitatively compare post-trial follow-up methods used in large randomised controlled trials. Five bibliographic databases, including Medline and the Cochrane Library, and one trial registry were searched. All large randomised controlled trials (more than 1000 adult participants) published from March 2006 to April 2017 were evaluated. Two reviewers screened and extracted data attaining > 95% concordance of papers checked. Assessment of bias in the trials was evaluated using the Cochrane Risk of Bias tool. RESULTS: Fifty-seven thousand three hundred and fifty-two papers were identified and 65 trials which had post-trial follow-up (PTFU) were included in the analysis. The majority of trials used more than one type of follow-up. There was no evidence of an association between the retention rates of participants in the PTFU period and the type of follow-up used. Costs of PTFU varied widely with data linkage being the most economical. It was not possible to assess associations between risk of bias during the in-trial period and proportions lost to follow-up during the PTFU period. DISCUSSION: Data captured during the post-trial follow-up period can add scientific value to a trial. However, there are logistical and financial barriers to overcome. Where available, data linkage via electronic registries and records is a cost-effective method which can provide data on a range of endpoints. SYSTEMATIC REVIEW REGISTRATION: Not applicable for PROSPERO registration

Long-term Clinical and Cost-effectiveness of Early Endovenous Ablation in Venous Ulceration: A Randomized Clinical Trial

Importance One-year outcomes from the Early Venous Reflux Ablation (EVRA) randomized trial showed accelerated venous leg ulcer healing and greater ulcer-free time for participants who are treated with early endovenous ablation of lower extremity superficial reflux.Objective To evaluate the clinical and cost-effectiveness of early endovenous ablation of superficial venous reflux in patients with venous leg ulceration.Design, Setting, and Participants Between October 24, 2013, and September 27, 2016, the EVRA randomized clinical trial enrolled 450 participants (450 legs) with venous leg ulceration of less than 6 months’ duration and superficial venous reflux. Initially, 6555 patients were assessed for eligibility, and 6105 were excluded for reasons including ulcer duration greater than 6 months, healed ulcer by the time of randomization, deep venous occlusive disease, and insufficient superficial venous reflux to warrant ablation therapy, among others. A total of 426 of 450 participants (94.7%) from the vascular surgery departments of 20 hospitals in the United Kingdom were included in the analysis for ulcer recurrence. Surgeons, participants, and follow-up assessors were not blinded to the treatment group. Data were analyzed from August 11 to November 4, 2019.Interventions Patients were randomly assigned to receive compression therapy with early endovenous ablation within 2 weeks of randomization (early intervention, n = 224) or compression with deferred endovenous treatment of superficial venous reflux (deferred intervention, n = 226). Endovenous modality and strategy were left to the preference of the treating clinical team.Main Outcomes and Measures The primary outcome for the extended phase was time to first ulcer recurrence. Secondary outcomes included ulcer recurrence rate and cost-effectiveness.Results The early-intervention group consisted of 224 participants (mean [SD] age, 67.0 [15.5] years; 127 men [56.7%]; 206 White participants [92%]). The deferred-intervention group consisted of 226 participants (mean [SD] age, 68.9 [14.0] years; 120 men [53.1%]; 208 White participants [92%]). Of the 426 participants whose leg ulcer had healed, 121 (28.4%) experienced at least 1 recurrence during follow-up. There was no clear difference in time to first ulcer recurrence between the 2 groups (hazard ratio, 0.82; 95% CI, 0.57-1.17; P = .28). Ulcers recurred at a lower rate of 0.11 per person-year in the early-intervention group compared with 0.16 per person-year in the deferred-intervention group (incidence rate ratio, 0.658; 95% CI, 0.480-0.898; P = .003). Time to ulcer healing was shorter in the early-intervention group for primary ulcers (hazard ratio, 1.36; 95% CI, 1.12-1.64; P = .002). At 3 years, early intervention was 91.6% likely to be cost-effective at a willingness to pay of £20 000 ($26 283) per quality-adjusted life year and 90.8$45 995) per quality-adjusted life year.Conclusions and Relevance Early endovenous ablation of superficial venous reflux was highly likely to be cost-effective over a 3-year horizon compared with deferred intervention. Early intervention accelerated the healing of venous leg ulcers and reduced the overall incidence of ulcer recurrence

How surgical Trainee Research Collaboratives achieve success: a mixed methods study to develop trainee engagement strategies

OBJECTIVES: This study aimed to understand the role of surgical Trainee Research Collaboratives (TRCs) in conducting randomised controlled trials and identify strategies to enhance trainee engagement in trials. DESIGN: This is a mixed methods study. We used observation of TRC meetings, semi-structured interviews and an online survey to explore trainees' motivations for engagement in trials and TRCs, including barriers and facilitators. Interviews were analysed thematically, alongside observation field notes. Survey responses were analysed using descriptive statistics. Strategies to enhance TRCs were developed at a workshop by 13 trial methodologists, surgical trainees, consultants and research nurses. SETTING: This study was conducted within a secondary care setting in the UK. PARTICIPANTS: The survey was sent to registered UK surgical trainees. TRC members and linked stakeholders across surgical specialties and UK regions were purposefully sampled for interviews. RESULTS: We observed 5 TRC meetings, conducted 32 semi-structured interviews and analysed 73 survey responses. TRCs can mobilise trainees thus gaining wider access to patients. Trainees engaged with TRCs to improve patient care, surgical evidence and to help progress their careers. Trainees valued the TRC infrastructure, research expertise and mentoring. Challenges for trainees included clinical and other priorities, limited time and confidence, and recognition, especially by authorship. Key TRC strategies were consultant support, initial simple rapid studies, transparency of involvement and recognition for trainees (including authorship policies) and working with Clinical Trials Units and research nurses. A 6 min digital story on YouTube disseminated these strategies. CONCLUSION: Trainee surgeons are mostly motivated to engage with trials and TRCs. Trainee engagement in TRCs can be enhanced through building relationships with key stakeholders, maximising multi-disciplinary working and offering training and career development opportunities

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362.Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow- up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2. 5% in each group for fatal or disabling stroke, and 5.3% with CAS versus 4.5% with CEA for any stroke (rate ratio [RR] 1.16, 95% CI 0.86-1.57; p=0 .33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1.11, 95% CI 0.91-1.32; p=0.21).Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable

Early Endarterectomy Carries a Lower Procedural Risk Than Early Stenting in Patients With Symptomatic Stenosis of the Internal Carotid Artery: Results From 4 Randomized Controlled Trials.

BACKGROUND AND PURPOSE: Patients undergoing carotid endarterectomy (CEA) for symptomatic stenosis of the internal carotid artery benefit from early intervention. Heterogeneous data are available on the influence of timing of carotid artery stenting (CAS) on procedural risk. METHODS: We investigated the association between timing of treatment (0-7 days and >7 days after the qualifying neurological event) and the 30-day risk of stroke or death after CAS or CEA in a pooled analysis of individual patient data from 4 randomized trials by the Carotid Stenosis Trialists' Collaboration. Analyses were done per protocol. To obtain combined estimates, logistic mixed models were applied. RESULTS: Among a total of 4138 patients, a minority received their allocated treatment within 7 days after symptom onset (14% CAS versus 11% CEA). Among patients treated within 1 week of symptoms, those treated by CAS had a higher risk of stroke or death compared with those treated with CEA: 8.3% versus 1.3%, risk ratio, 6.7; 95% confidence interval, 2.1 to 21.9 (adjusted for age at treatment, sex, and type of qualifying event). For interventions after 1 week, CAS was also more hazardous than CEA: 7.1% versus 3.6%, adjusted risk ratio, 2.0; 95% confidence interval, 1.5 to 2.7 (P value for interaction with time interval 0.06). CONCLUSIONS: In randomized trials comparing stenting with CEA for symptomatic carotid artery stenosis, CAS was associated with a substantially higher periprocedural risk during the first 7 days after the onset of symptoms. Early surgery is safer than stenting for preventing future stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00190398; URL: http://www.controlled-trials.com. Unique identifier: ISRCTN57874028; Unique identifier: ISRCTN25337470; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732