International Journal of Surgery 25 (2016) 38e43
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The perception of scar cosmesis following thyroid and parathyroid surgery: A prospective cohort study Asit Arora a, *, Chloe Swords a, George Garas a, Konstantinos Chaidas a, Alexa Prichard a, James Budge a, D. Ceri Davies b, Neil Tolley a a b
Department of Otorhinolaryngology and Head & Neck Surgery, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, W2 1NY, UK Human Anatomy Unit, Department of Surgery and Cancer, Imperial College London, W6 8RP, UK
h i g h l i g h t s Scar-related issues are not uncommon following thyroid and parathyroid surgery. No correlation was found between scar length and patient satisfaction. The perception of an acceptable cosmetic result differs between patient and clinician. Asian and Afro-Caribbean ethnicity and a malignant diagnosis were associated with a poor cosmetic outcome. The majority of patients would choose to avoid a neck scar given the option.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 6 July 2015 Received in revised form 24 October 2015 Accepted 15 November 2015 Available online 19 November 2015
Introduction: Various “scarless” approaches have been described for thyroid and parathyroid surgery. The objective of the current study was to investigate patients' perception of neck scar cosmesis, its impact on quality of life (QoL) and evaluate patient preference with regards to scar location. Methods: 120 patients undergoing thyroid or parathyroid surgery were followed-up over a 5-year period (2008e2013). Validated tools were used to assess scar perception and its impact on QoL. These were evaluated against sex, age, ethnicity, operation type, histopathology, time following surgery and scar length. Results: Mean follow-up was 2.6 ± 3.8 years. One of the most common post-operative problems was scar-related (n ¼ 18). Caucasian patients and those with benign histology expressed a lower impact on QoL (p < 0.001, p ¼ 0.038). Sex and scar length did not signiﬁcantly affect patients' perception for scar cosmesis (p > 0.05). Clinicians tended to score scar cosmesis higher than patients (p ¼ 0.02). Most participants (75%) expressed a clear preference for an extracervical “scar-less in the neck” approach. Discussion: Scar-related issues are frequently reported following thyroid and parathyroid surgery. The negative impact, often underestimated by clinicians, is more apparent amongst Asian and Afro-Caribbean patients and can signiﬁcantly impact on their QoL. This, combined with the lack of correlation between scar length and patient satisfaction, indicates the need to divert research from miniaturising neck scars to concealing them in extracervical sites. Conclusion: Patients prefer a scar-less in the neck approach when given the option. A prospective comparative study is required to compare the cervical and extracervical approaches. © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.
Keywords: Scar cosmesis Robotic Thyroidectomy Parathyroidectomy Quality of life
* Corresponding author. Department of Otorhinolaryngology and Head & Neck Surgery, St Mary's Hospital, Imperial College Healthcare NHS Trust, Praed Street, London, W2 1NY, UK. E-mail address: [email protected]
The standard approach to thyroidectomy uses an anterior neck incision known as “Kocher incision” that is usually 6e8 cm long . In experienced hands, this approach leads to high success rates and low morbidity. However, thyroid surgery is continuously evolving in response to a number of concerns [1,2]. A particular concern with
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A. Arora et al. / International Journal of Surgery 25 (2016) 38e43
the Kocher incision is the possibility of scarring in the exposed anterior neck. Although in the majority of patients the incision heals well, a proportion of patients are left with a noticeable, aesthetically unattractive and psychologically distressing scar . Individual patient characteristics such as age, race and sex can inﬂuence scar characteristics and its associated cosmetic perception. As a result, a multitude of surgical techniques have been described in an attempt to reduce the scar-related morbidity associated with thyroid surgery . Minimally invasive video-assisted thyroidectomy (MIVAT) developed by Miccoli  is currently the most widely used minimal access technique. Despite MIVAT utilising a smaller incision, a visible neck scar remains. Extracervical endoscopic techniques for thyroid surgery were developed to address this exact problem. Although the literature supports “scarless” (in the neck) endoscopic thyroidectomy (SET) over conventional thyroidectomy in terms of its perceived aesthetic outcome [1,2], SET techniques have signiﬁcant limitations due to the 2-dimensional view obtained and rigid instrumentation involved. Those ergonomic limitations have hindered the widespread adoption of SET. SET was re-popularised in 2009, when a group from South Korea led by Chung pioneered the technique of robotic axillary thyroidectomy (RAT) using the da Vinci® robot (Intuitive Surgical, Inc, Sunnyvale, CA) [6,7]. Robotic instrumentation offers numerous advantages over both conventional and endoscopic thyroidectomy [8,9]. In addition to a “scarless” approach, the robotic system offers a superior 3-dimensional view associated with increased precision, tremor ﬁltration, and greater articulation . Despite these advantages, RAT also has some important disadvantages compared to conventional thyroidectomy approaches. Far from being minimally invasive, the robotic transaxillary approach to the thyroid gland involves additional dissection and an associated potential risk to neurovascular structures. Despite extensive research into novel, “scarless” techniques, little is known about scar perception following conventional thyroid and parathyroid surgery. Moreover, the relationship between patients' and healthcare professionals' impression of scars is poorly understood. Consequently, before offering a RAT approach, it is fundamental to understand and consider the patients' perceptions and attitudes. The objectives of this study were threefold: (1) to investigate patients' scar perception following conventional thyroid and parathyroid surgery in a UK population; (2) explore patients' attitudes towards “scar-less in the neck” surgery and (3) compare clinician to patient perception for the same scars. Particular attention was paid to the effects of sex, age and ethnicity on patients' perceptions and to the impact of scars on patients' quality of life (QoL). 2. Methods Patients who underwent conventional thyroid or parathyroid surgery at St. Mary's Hospital, London, UK were surveyed over a 5year period (December 2008eJanuary 2013). A total of 120 patients consented to be evaluated. This was a prospective study that evaluated outcome measures as part of routine post-operative follow-up. Patients younger than 16 years of age, those with a history of radiotherapy to the head and neck and those who had also undergone lateral compartment neck dissection were excluded from the study. With regards to cervical incision planning, this was based on whether an obvious skin crease was present on the patient's neck and the size of the thyroid nodule or parathyroid adenoma to be excised. Incision length was kept to a minimum (usually about 4 cm) though long enough to allow delivery of the lesion. The
incision was always planned to be symmetrical with respect to the midline so as not to “catch the eye”. If an obvious skin crease was present, then this was opted for. If not, a suture was used to mark the incision which was commonly located around the cricoid area. A high incision is generally preferred for 3 reasons: (1) we believe it is cosmetically superior; (2) it improves access to the superior poles, the most challenging area to dissect during thyroid surgery and (3) in the event that the histopathological examination result of the excised specimen comes back as malignant and a neck dissection is required at a later stage, a high incision can be easily extended along the relaxed skin tension lines. In contrast, a low incision will necessitate superior diversion causing it to transgress the relaxed skin tension lines (i.e. extend across rather than along them) thus compromising wound healing in addition to being longer, wider and curved. Wound closure was standardised for all patients comprising of 3-layer closure with interrupted 4-0 Vicryl sutures for the strap and platysma muscles followed by continuous 5-0 Vicryl Rapide subcuticular sutures. Following skin closure, Dermabond (Ethicon Endo-Surgery, Inc) tissue glue was applied on the wound. No drains were used. Post-operative wound management was identical throughout the cohort (standard wound care, no antibiotic ointment used routinely). To quantify scar perception, a visual analogue scale (VAS) was used. This has been validated for the assessment of linear postoperative scars . It can reliably discriminate between different types of scar quality and accurately evaluate patient satisfaction regarding scar cosmesis. Three sets of data were collected. 2.1. Demographic data Details including age, sex and ethnicity were recorded (Appendix A). Other information included time elapsed since surgery and operation type. Post-operative complications, including hypertrophic and keloid scar formation, were recorded in free text. Histopathology data was collected using electronic medical records. The records were incomplete for 15 patients. 2.2. Patient self-assessment Patients were asked to assess their scar as it appeared at particular time intervals following surgery (Appendix B). A VAS was used, where 0 indicated the poorest scar (completely unsatisﬁed) and 10, a “perfect” scar (completely satisﬁed). Patients were also asked to quantify the effect of the scar on their QoL using a VAS (where 0 indicated no effect and 10, a major effect). Patients were also given the opportunity to make free text comments. In addition, patients' attitudes to scar location (cervical or extracervical) were evaluated using the following question: “if all else were equal between surgical sites (i.e. recovery time, complications, etc.), which site, as indicated by the diagram, would you opt for?” The patients were subsequently given a pictorial representation of 4 anatomical scar sites; upper neck, lower neck, infraclavicular area and axilla, and asked to rank the 4 sites from 1 (most preferred) to 4 (least preferred) (see Appendix C). 2.3. Independent observer assessment This involved a subjective blind evaluation of a patient's scar by 3 independent assessors: an ENT e Head & Neck surgeon, an endocrinologist and a medical student. The same VAS tool used for patient self-assessment was employed (Appendix D). This was performed on 44 patients, when all 3 evaluators were available in the clinic to assess the scar.
A. Arora et al. / International Journal of Surgery 25 (2016) 38e43
2.4. Statistical analysis Values are reported as mean ± standard error of the mean (SEM). Comparison of nonparametric data was performed with the ManneWhitney U Test for two variables, and the KruskaleWallis test for groups with more than two. Multiple linear regression analysis and partial correlation were performed to determine whether independent demographic and surgical characteristics were predictors of the VAS score. Possible factors considered in the logistic regression were age, sex, follow-up time, ethnicity, operation type, histopathology, and scar length. This was performed for both scar and QoL VAS scar scores. The Wilcoxon signed rank test was used to assess differences in VAS scar scores between patients and individual scores of the 3 independent observers. Pearson's correlation was carried out to identify any association between scar length and VAS self-assessment scar score. Signiﬁcance was ascribed to any p-value less than 0.05. All statistical analyses were performed using SPSS® software v21.0 (SPSS Inc., Chicago, IL). The research method was fully compliant with the STROBE criteria and was registered with the Research Registry UIN (protocol number 373). 3. Results 3.1. Demographics The majority of patients investigated were female (n ¼ 101; 84%) and their mean age (±SEM) at the time of surgery was 51.8 ± 1.3 years. Thirty-three patients (27.5%) described themselves as Caucasian. Forty-nine patients (40.8%) described their ethnicity as non-Caucasian and 38 patients (31.7%) did not declare their ethnicity. Demographic characteristics are shown in Table 1. 3.2. Surgical characteristics The mean time (±SEM) elapse between surgery and scar evaluation was 2.6 ± 3.8 years. The majority of participants (n ¼ 96, 80%) had undergone thyroid surgery: 34 (28%) having undergone thyroid lobectomy and 62 (52%) total thyroidectomy. Twenty-four patients (20%) underwent parathyroidectomy for primary hyperparathyroidism. Twenty-three patients (19%) developed post-operative complications. The most commonly reported problems were scar-related (n ¼ 18). The incidence of hypertrophic scars was 12.5% (n ¼ 15). Of those patients with hypertrophic scars, 27% (n ¼ 4) did not Table 1 Demographic characteristics of study cohort. Patient ethnicity is divided into those who described their ethnicity as Caucasian and those who describe their ethnicity as non-Caucasian. Characteristic Sex Male Female Age at surgery, years 0e19 20e39 40e59 >60 Ethnicity Caucasian Non-Caucasian Afro-Carribean Asian South American Not declared
Number of patients (%) 19 (15.8%) 101 (84.2%) Mean (±SEM): 51.8(1.3) 0 (0%) 28 (23.3%) 53 (44.2%) 39 (32.5%) 33 (27.5%) 49 (40.8%) 20 (16.7%) 27 (22.5%) 2 (1.7%) 38 (31.7%)
declare their ethnicity. The majority of the remaining 11 patients with scar-related issues were of Afro-Caribbean or Asian ethnicity (82%). Non-hypertrophic scar-related issues were cited by 3 patients and included scar discomfort, itching and burning. Other complications included 3 patients who developed recurrent laryngeal nerve (RLN) neurapraxia, all of which resolved within 3 months of surgery. Two patients developed a haematoma that required surgical evacuation. Calcium related problems were not recorded. Surgical characteristics are shown in Table 2. 3.3. Patient assessment The mean VAS score for scar self-assessment across the entire cohort was 6.6 ± 2.9 (range: 1e10). The effect of independent variables on the VAS scar score is presented in Table 3. Mean VAS score improved signiﬁcantly with advanced patient age and progressive time elapsed following surgery. Patients over 60 years were more likely to rate their scars positively (p ¼ 0.045). The statistical signiﬁcance remained even after controlling for all confounding factors (p ¼ 0.011, dF ¼ 46). The perception of scar appearance improved over time; patients gave their scars the highest VAS score between 9 and 24 months following surgery (p ¼ 0.004). Beyond this timeframe, the scar assessment score did not improve. There was a statistically signiﬁcant difference between the mean VAS score of patients diagnosed with benign compared to malignant pathology as patients with a diagnosis of differentiated thyroid cancer (DTC) rated their scar worse than those with benign disease (p ¼ 0.003). The mean VAS score was signiﬁcantly higher in patients who underwent parathyroidectomy compared to those who underwent thyroidectomy (p ¼ 0.048). The average scar length was 5.84 cm (range: 2.5e10 cm). There was no signiﬁcant correlation between scar length and patient satisfaction with scar appearance (p ¼ 0.535). There was no effect of sex on mean scar VAS score (p ¼ 0.818). 3.4. Impact on quality of life Across the entire cohort, the mean VAS score for impact on QoL was 1.9 ± 2.4 (where 0 indicated no effect and 10 a major effect). The impact of the scar upon a patient's QoL was signiﬁcantly higher in those patients that experienced scar-related complications (p ¼ 0.004). Ethnicity also signiﬁcantly impacted on QoL. NonCaucasian patients reported a signiﬁcantly higher (negative) impact on their QoL than those of Caucasian background (p < 0.001). The statistical signiﬁcance remained after controlling for all other potentially confounding factors (p ¼ 0.031, dF ¼ 46). Similarly, after controlling for confounding factors, the impact of scar upon QoL was signiﬁcantly more in patients diagnosed with malignant compared to benign pathology (p ¼ 0.038, dF ¼ 46). There was no signiﬁcant difference between the VAS QoL scores with increasing time at follow-up (p ¼ 0.192) and for older patients (p ¼ 0.209). 3.5. Scar location 105 patients provided information regarding scar location (15 patients returned incomplete questionnaires). The majority (n ¼ 79, 75%) expressed a clear preference for an extracervical scar. This was irrespective of ethnic origin (p ¼ 0.739). Given the choice, most patients (n ¼ 70, 89%) opted for an axillary approach over an infraclavicular incision. Of the remaining 26 patients choosing a cervical approach, the majority (n ¼ 23, 88%) expressed a preference for a lower compared to an upper neck scar (Fig. 1).
A. Arora et al. / International Journal of Surgery 25 (2016) 38e43
Table 2 Surgical characteristics of study cohort. DTC: differentiated thyroid cancer. Q1 (quartile 1, 25%); IQR (interquartile range); Q2 (quartile 2, 75%). Characteristic
Number of patients (%)
Operation Hemi-thyroidectomy Total thyroidectomy Parathyroidectomy Postoperative complications None Hypertrophic/keloid scar Other scar-related Vocal cord palsy Haematoma Histopathology DTC Non-cancerous Not speciﬁed Age of scar at follow-up evaluation (months) <1 1e3 3e9 9 -24 >24 Not recorded Average scar length (cm)
34 (28.3%) 62 (51.7%) 24 (20%) 97 (81%) 15 (12.5%) 3 (2.5%) 3 (2.5%) 2 (1.5%) 48 (40%) 57 (47.5%) 15 (12.5%) Mean ± SEM: 30.925 ± 4.3 Median: 12 (Q1: 2.27, IQR: 38.4, Q2: 40.67) 16 (13.3%) 16 (13.3%) 13 (10.8%) 32 (26.7%) 41 (34.2%) 2 (1.7%) Mean ± SD: 5.84 ± 1.71 Range: 2.5e10
Table 3 Independent variables and scar score (VAS). Data are mean ± standard error of mean (SEM). The asterisk signiﬁes statistically signiﬁcant results whereby p < 0.05.
Patient characteristics Sex Male Female Age (years) 20-39 40-59 >60 Ethnicity Caucasian Non-Caucasian Surgical characteristics Operation Thyroid surgery Parathyroid surgery Histopathology DTC Benign Age of scar < 1 month 1e3 months 3e9 months 9e24 months > 24 months Scar length (cm)
Cosmetic satisfaction score
28 53 39
5.74 6.49 7.48
0.6 0.4 0.43
p value 0.818
0.003* 48 57
16 16 13 32 41 105
5.28 5.06 7.43 7.75 6.68 6.4
0.81 0.65 0.87 0.4 0.47 0.31
Fig. 1. Patient preference for scar location. Patients were asked to rank the sites (upper neck, lower neck, upper chest (infraclavicular), axilla) as 1 (most preferred) to 4 (least preferred) (see Appendix 2). Fig. 1 illustrates the breakdown of patient preferences for each site.
3.6. Independent observer assessment The mean VAS self-observed scar score for the subset of patients assessed (n ¼ 44) was 5.7 ± 3.0. This subset of patients was deﬁned by those assessed when all independent medical evaluators were available in the same multidisciplinary clinic. The endocrinologist rated the scars signiﬁcantly better than the patients (p ¼ 0.02). There was no statistically signiﬁcant difference between the ENT surgeons and medical students when compared to patients (Fig. 2).
This study evaluated the long-term results of conventional thyroid and parathyroid surgery to help guide the development of robotic thyroid and parathyroid surgery. The most important outcome measure was patient satisfaction with scar cosmesis and ranking of patient choice for scar location. Additionally, the main sociodemographic and surgical factors that impacted upon scar cosmesis and QoL were identiﬁed. Cohort demographics were broadly in keeping with the proﬁle associated with thyroid and parathyroid disorders, i.e. predominantly females with a modal age distribution in the 4th decade of life [12,13]. Almost half of the group were of Afro-Caribbean, Asian and South American ethnicity, reﬂecting the ethnic diversity of the patient population in the local region of London. Patients were recruited from a tertiary referral hospital which accounts for the relatively high proportion (nearly half) of patients being diagnosed with DTC.
A. Arora et al. / International Journal of Surgery 25 (2016) 38e43
10 9 p = 0.02
Mean VAS scar score
4 3 2 1 0 Patient
Fig. 2. Independent observer compared to patient assessment of the neck scar. A high score is desirable (0 indicates completely unsatisﬁed; 10 indicates completely satisﬁed).
First and foremost, the results of this study highlight the importance of taking the patient's perception of their scar into account when researching techniques for future surgical approaches. Previous studies have shown that clinicians often fail to consider how patients' opinion impacts on their practice [14,15]. Our results indicate that what may appear to be an acceptable cosmetic result to the clinician may not necessarily translate to the patient's perception of their scar: endocrinologists rated scar appearance better than the patients (p ¼ 0.02). Therefore, it is important to ask for the patient's opinion of their scar in an effort to identify what is important and which factors have an inﬂuence on scar cosmesis. Our results indicate that a variety of factors impact on scar perception but of equal interest are those factors which do not seem to alter the results. Patients for whom a greater time period had elapsed since surgery were more satisﬁed with their scars, a ﬁnding reinforcing the fact that scars generally improve with time. However, after 2 years, no further improvement was observed. The cellular processes that underpin scar remodelling are most active during the ﬁrst 3 months after the creation of a wound . However, scar remodelling remains active well beyond this period. Sahm et al.  stated that assessment of the scar during the ﬁrst 6 months following surgery may be misleading as scars do not reach their ﬁnal appearance until after this time. Those ﬁndings are reﬂected in this study where patients assessed at 3 or fewer months postoperatively were less satisﬁed with their scars. A major driving force behind techniques of minimally invasive thyroid surgery is that a small incision is assumed to improve patient satisfaction. The published literature on MIVAT describes the average central incision between 1 and 3 cm . In this study, no correlation was found between scar length and patient scar satisfaction. Similar ﬁndings have been reported for patients following thyroid and parathyroid surgery in other studies [18,19]. This suggests that the drive to miniaturise scars may be unnecessary, as patient scar satisfaction appears to be independent of scar length. A key problem with long-term scar cosmesis is hypertrophic and keloid scarring [20,21]. Darkly pigmented skin is the primary risk factor, with individuals of Asian, Afro-Caribbean and South American ethnicity being far more likely to experience this complication than their Caucasian counterparts . In this study, 15 patients developed hypertrophic scars. 82% of these patients (9/11) were of Asian, Afro-Caribbean and Hispanic ethnicity. Moreover, the impact of ethnicity upon a patient's QoL was signiﬁcantly higher in those of Afro-Caribbean, Asian or South American origin (p < 0.001). These ﬁndings are compatible with other reports .
The mean scar rating of patients with a diagnosis of cancer was shown to be far worse than those with benign disease (p ¼ 0.03). A recent study investigated the impact of post-thyroidectomy scars on the QoL of thyroid cancer patients . The authors concluded that scars on the neck negatively affected the QoL of thyroid cancer patients. Moreover, the Thyroid Cancer Alliance published an article assessing the experience of thyroid cancer patients worldwide . In this multinational cross-sectional survey, patients with thyroid cancer were found to suffer signiﬁcant post-treatment psychosocial morbidity. Previous studies have explored the importance of supporting a patient's psychosocial requirements and the negative impact of failing to do so . One possible explanation is that when faced with a diagnosis of cancer, the patient's psyche may negatively impact upon their scar satisfaction. Patients who underwent parathyroidectomy rated their scar more favourably. This ﬁnding is unlikely to be due to scar size differences, as patient scar satisfaction remains independent of scar length. A potential reason for the difference in scar satisfaction is the underlying benign parathyroid pathology (100% (n ¼ 24) parathyroidectomies were performed for primary hyperparathyroidism) compared to the thyroid group (DTC 50% (n ¼ 48); benign 34% (n ¼ 33); not recorded 16% (n ¼ 15)). Our results regarding impact of histology on scar satisfaction score indicate that patients with benign pathology are more satisﬁed with their scar. An interesting avenue to explore would be to ask patients to quantify the impact of diagnosis pre-operatively (in terms of associated medical symptoms, such as those of hyperparathyroidism or hyperthyroidism) and compare these to their post-operative QoL scores. Scar location underpins the rationale for offering patients robotic axillary thyroid and parathyroid surgery [27,28]. A recent study compared the impact of postoperative scars . The authors concluded that the QoL in patients with visible scars is poorer than in those where the scar is hidden. This study concludes that a clear majority (75%) of patients expressed a preference for a scarless in the neck approach, with an axillary scar being the preferred extracervical site. The ﬁndings of this study are compatible with those of a recent UK study that investigated the patient perspective of morbidity following thyroid surgery by means of a postal questionnaire sent to 312 patients . Approximately 65% of the responders stated they would deﬁnitely/maybe be interested in a scarless in the neck approach. On the other hand, conﬂicting results have been reported from another large study (n ¼ 596) where only a small proportion (11.6%) of patients surveyed would have opted for a robotic approach . The main criticism of the latter study is that the authors informed the study population that “major drawbacks of this technique compared with conventional thyroidectomy are the longer duration of the procedure, higher postoperative pain, and higher cost”. There are certain limitations in this study that are worth considering. The most important relates to a selection bias associated with patient recruitment. Secondly, the long average time at follow-up biases the cohort towards those suffering from malignant disease or a complex post-operative course. However, this limitation is advantageous in terms of evaluating scars once wounds have fully healed. Another limitation relates to the sociodemographic characteristics as ethnicity rather than an objective measure of skin colour, such as the Fitzpatrick skin classiﬁcation, was used . Finally, group heterogeneity needs to be acknowledged as thyroid and parathyroid surgery patients were analysed as one cohort. Nevertheless, this is clinically meaningful as both thyroid and parathyroid disorders are treated by the same surgical specialty.
A. Arora et al. / International Journal of Surgery 25 (2016) 38e43
5. Conclusion This study shows that scar-related issues represent one of the most frequently reported problems following thyroid and parathyroid surgery. Patient perception of scar cosmesis and its associated impact upon QoL is signiﬁcant and often underestimated by clinicians. The preference for an axillary incision was evident in this patient cohort. On the basis of this, and the clinical data emerging from South Korea regarding robotic axillary thyroidectomy, the next step will be to perform a head-to-head prospective comparison regarding long-term scar cosmesis and QoL between conventional and robotic axillary thyroidectomy patients in a UK population.
Ethical approval 
UIN 373. Favourable approval from the National Health Service (NHS) Health Research Authority (National Research Ethics Service Committee London). Protocol Reference Number: 08/H0721/97.
Source of funding 
Nothing to declare. 
Author contribution Asit Arora: study design, data collection, writing. Chloe Swords: data collection, data analysis, writing. George Garas: data collection, data analysis, writing. Konstantinos Chaidas: data collection, data analysis. Alexa Prichard: data collection, data analysis. James Budge: data collection, data analysis. D. Ceri Davies: study design, writing. Neil Tolley: study design, data collection, writing. Conﬂicts of interest Nothing to declare. Research registry UIN 373. Guarantor
Asit Arora. 
Appendix A. Supplementary data 
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