Injection fears and COVID-19 vaccine hesitancy.

BACKGROUND: When vaccination depends on injection, it is plausible that the blood-injection-injury cluster of fears may contribute to hesitancy. Our primary aim was to estimate in the UK adult population the proportion of COVID-19 vaccine hesitancy explained by blood-injection-injury fears. METHODS: In total, 15 014 UK adults, quota sampled to match the population for age, gender, ethnicity, income and region, took part (19 January-5 February 2021) in a non-probability online survey. The Oxford COVID-19 Vaccine Hesitancy Scale assessed intent to be vaccinated. Two scales (Specific Phobia Scale-blood-injection-injury phobia and Medical Fear Survey-injections and blood subscale) assessed blood-injection-injury fears. Four items from these scales were used to create a factor score specifically for injection fears. RESULTS: In total, 3927 (26.2%) screened positive for blood-injection-injury phobia. Individuals screening positive (22.0%) were more likely to report COVID-19 vaccine hesitancy compared to individuals screening negative (11.5%), odds ratio = 2.18, 95% confidence interval (CI) 1.97-2.40, p < 0.001. The population attributable fraction (PAF) indicated that if blood-injection-injury phobia were absent then this may prevent 11.5% of all instances of vaccine hesitancy, AF = 0.11; 95% CI 0.09-0.14, p < 0.001. COVID-19 vaccine hesitancy was associated with higher scores on the Specific Phobia Scale, r = 0.22, p < 0.001, Medical Fear Survey, r = 0.23, p = <0.001 and injection fears, r = 0.25, p < 0.001. Injection fears were higher in youth and in Black and Asian ethnic groups, and explained a small degree of why vaccine hesitancy is higher in these groups. CONCLUSIONS: Across the adult population, blood-injection-injury fears may explain approximately 10% of cases of COVID-19 vaccine hesitancy. Addressing such fears will likely improve the effectiveness of vaccination programmes.

COVID-19 vaccine hesitancy in the UK: the Oxford coronavirus explanations, attitudes, and narratives survey (Oceans) II.

BACKGROUND: Our aim was to estimate provisional willingness to receive a coronavirus 2019 (COVID-19) vaccine, identify predictive socio-demographic factors, and, principally, determine potential causes in order to guide information provision. METHODS: A non-probability online survey was conducted (24th September-17th October 2020) with 5,114 UK adults, quota sampled to match the population for age, gender, ethnicity, income, and region. The Oxford COVID-19 vaccine hesitancy scale assessed intent to take an approved vaccine. Structural equation modelling estimated explanatory factor relationships. RESULTS: 71.7% (n=3,667) were willing to be vaccinated, 16.6% (n=849) were very unsure, and 11.7% (n=598) were strongly hesitant. An excellent model fit (RMSEA=0.05/CFI=0.97/TLI=0.97), explaining 86% of variance in hesitancy, was provided by beliefs about the collective importance, efficacy, side-effects, and speed of development of a COVID-19 vaccine. A second model, with reasonable fit (RMSEA=0.03/CFI=0.93/TLI=0.92), explaining 32% of variance, highlighted two higher-order explanatory factors: 'excessive mistrust' (r=0.51), including conspiracy beliefs, negative views of doctors, and need for chaos, and 'positive healthcare experiences' (r=-0.48), including supportive doctor interactions and good NHS care. Hesitancy was associated with younger age, female gender, lower income, and ethnicity, but socio-demographic information explained little variance (9.8%). Hesitancy was associated with lower adherence to social distancing guidelines. CONCLUSIONS: COVID-19 vaccine hesitancy is relatively evenly spread across the population. Willingness to take a vaccine is closely bound to recognition of the collective importance. Vaccine public information that highlights prosocial benefits may be especially effective. Factors such as conspiracy beliefs that foster mistrust and erode social cohesion will lower vaccine up-take.

Effects of different types of written vaccination information on COVID-19 vaccine hesitancy in the UK (OCEANS-III): a single-blind, parallel-group, randomised controlled trial.

BACKGROUND: The effectiveness of the COVID-19 vaccination programme depends on mass participation: the greater the number of people vaccinated, the less risk to the population. Concise, persuasive messaging is crucial, particularly given substantial levels of vaccine hesitancy in the UK. Our aim was to test which types of written information about COVID-19 vaccination, in addition to a statement of efficacy and safety, might increase vaccine acceptance. METHODS: For this single-blind, parallel-group, randomised controlled trial, we aimed to recruit 15 000 adults in the UK, who were quota sampled to be representative. Participants were randomly assigned equally across ten information conditions stratified by level of vaccine acceptance (willing, doubtful, or strongly hesitant). The control information condition comprised the safety and effectiveness statement taken from the UK National Health Service website; the remaining conditions addressed collective benefit, personal benefit, seriousness of the pandemic, and safety concerns. After online provision of vaccination information, participants completed the Oxford COVID-19 Vaccine Hesitancy Scale (outcome measure; score range 7-35) and the Oxford Vaccine Confidence and Complacency Scale (mediation measure). The primary outcome was willingness to be vaccinated. Participants were analysed in the groups they were allocated. p values were adjusted for multiple comparisons. The study was registered with ISRCTN, ISRCTN37254291. FINDINGS: From Jan 19 to Feb 5, 2021, 15 014 adults were recruited. Vaccine hesitancy had reduced from 26·9% the previous year to 16·9%, so recruitment was extended to Feb 18 to recruit 3841 additional vaccine-hesitant adults. 12 463 (66·1%) participants were classified as willing, 2932 (15·6%) as doubtful, and 3460 (18·4%) as strongly hesitant (ie, report that they will avoid being vaccinated for as long as possible or will never get vaccinated). Information conditions did not alter COVID-19 vaccine hesitancy in those willing or doubtful (adjusted p values >0·70). In those strongly hesitant, COVID-19 vaccine hesitancy was reduced, in comparison to the control condition, by personal benefit information (mean difference -1·49, 95% CI -2·16 to -0·82; adjusted p=0·0015), directly addressing safety concerns about speed of development (-0·91, -1·58 to -0·23; adjusted p=0·0261), and a combination of all information (-0·86, -1·53 to -0·18; adjusted p=0·0313). In those strongly hesitant, provision of personal benefit information reduced hesitancy to a greater extent than provision of information on the collective benefit of not personally getting ill (-0·97, 95% CI -1·64 to -0·30; adjusted p=0·0165) or the collective benefit of not transmitting the virus (-1·01, -1·68 to -0·35; adjusted p=0·0150). Ethnicity and gender were found to moderate information condition outcomes. INTERPRETATION: In the approximately 10% of the population who are strongly hesitant about COVID-19 vaccines, provision of information on personal benefit reduces hesitancy to a greater extent than information on collective benefits. Where perception of risk from vaccines is most salient, decision making becomes centred on the personal. As such, messaging that stresses the counterbalancing personal benefits is likely to prove most effective. The messaging from this study could be used in public health communications. Going forwards, the study highlights the need for future health campaigns to engage with the public on the terrain that is most salient to them. FUNDING: National Institute for Health Research (NIHR) Oxford Biomedical Research Centre and NIHR Oxford Health Biomedical Research Centre.

Norepinephrine promotes tumor microenvironment reactivity through ß3-adrenoreceptors during melanoma progression.

Stress has an emerging role in cancer and targeting stress-related ß-adrenergic receptors (AR) has been proposed as a potential therapeutic approach in melanoma. Here we report that ß3-AR expression correlates with melanoma aggressiveness. In addition, we highlight that ß3-AR expression is not only restricted to cancer cells, but it is also expressed in vivo in stromal, inflammatory and vascular cells of the melanoma microenvironment. Particularly, we demonstrated that ß3-AR can (i) instruct melanoma cells to respond to environmental stimuli, (ii) enhance melanoma cells response to stromal fibroblasts and macrophages, (iii) increase melanoma cell motility and (iv) induce stem-like traits. Noteworthy, ß3-AR activation in melanoma accessory cells drives stromal reactivity by inducing pro-inflammatory cytokines secretion and de novo angiogenesis, sustaining tumor growth and melanoma aggressiveness. ß3-ARs also play a mandatory role in the recruitment to tumor sites of circulating stromal cells precursors, in the differentiation of these cells towards different lineages, further favoring tumor inflammation, angiogenesis and ultimately melanoma malignancy. Our findings validate selective ß3-AR antagonists as potential promising anti-metastatic agents. These could be used to complement current therapeutic approaches for melanoma patients (e.g. propranolol) by targeting non-neoplastic stromal cells, hence reducing therapy resistance of melanoma.

ß-adrenoceptors are upregulated in human melanoma and their activation releases pro-tumorigenic cytokines and metalloproteases in melanoma cell lines.

Recent studies sight ß-adrenergic receptor (AR) antagonists as novel therapeutic agents for melanoma, as they may reduce disease progression. Here within, we evaluated the expression of ß-ARs in a series of human cutaneous melanocytic lesions, and studied the effect of their endogenous agonists, norepinephrine (NE) and epinephrine (E), on primary and metastatic human melanoma cell lines. Using immunohistochemistry, we found that both ß1- and ß2-ARs are expressed in tissues from benign melanocytic naevi, atypical naevi and malignant melanomas and that expression was significantly higher in malignant tumours. Melanoma cell lines (human A375 primary melanoma cell line and human Hs29-4T metastatic melanoma cell lines) also expressed ß1- and ß2-ARs by measuring transcripts and proteins. NE or E increased metalloprotease-dependent motility, released interleukin-6 and 8 (IL-6, IL-8) and vascular endothelial growth factor (VEGF). These effects of catecholamines were inhibited by the unselective ß-AR antagonist propranolol. The role of soluble factors elicited by catecholamines seemed pleiotropic as VEGF synergized with NE increased melanoma invasiveness through 3D barriers, while IL-6 participated in stromal fibroblast activation towards a myofibroblastic phenotype. Our results indicate that NE and E produce in vitro via ß-ARs activation a number of biological responses that may exert a pro-tumorigenic effect in melanoma cell lines. The observation that ß-ARs are upregulated in malignant melanoma tissues support the hypothesis that circulating catecholamines NE and E, by activating their receptors, favour melanoma progression in vivo.

Recurrent distal digital keratoacanthoma of the periungual region treated with Mohs micrographic surgery.

We report a 42-year-old man who presented with a recurrent painful nodule on the proximal nail fold of the left fifth finger. The tumour had been surgically excised at another department a month earlier, and histological examination had shown a keratoacanthoma. The patient underwent Mohs micrographic surgery, and no recurrence was evident 16 months later. Mohs micrographic surgery appears to be an effective option in the management of this unusual variant of keratoacanthoma, which is often difficult to eradicate.

Comparison of the manual and computer-aided techniques for evaluation of wrist synovitis using dynamic contrast-enhanced MRI on a dedicated scanner.

OBJECTIVE: Traditional methods for assessment of synovial inflammation in rheumatoid arthritis such as clinical examination, immunohistology of bioptic samples, scintigraphy, and radiography have several limitations, including lack of sensitivity, need of invasive techniques, and administration of radioactive material. MRI lacks on standardisation and the data are often analysed using laborious, relatively rigid scoring methods. MATERIALS AND METHODS: This study introduces a standardized computer-aided method for quantitative analysis of MRI of the wrist on a dedicated scanner. Assessment of the synovial inflammation was performed using a semi-automated model-based method in conjunction with patient motion reduction algorithms. Further, the new method was compared with the traditional user-dependent ROI-based technique. RESULTS: The computer-aided technique generated robust and reproducible results. Application of motion reduction algorithms allowed for significant improvements of the signal to noise ratio, which is especially important in the datasets acquired with low-field scanners. CONCLUSION: The use of the computer software can be beneficial for diagnostic decision in cross sectional as well as longitudinal MRI examinations of the wrist in rheumatoid arthritis.

Tumour regression does not increase the risk of sentinel node involvement in thin melanomas.

Few studies have analysed the relationship between tumour regression and risk of nodal metastasis in patients with thin melanomas (Breslow thickness < or = 1 mm), and the conclusions reported have been conflicting. The aim of this study was to evaluate the role of histological regression as a predictor of lymph node metasta- sis in a selected group of patients with thin melanomas, submitted to lymphatic mapping and sentinel lymph node biopsy. From November 1999 to November 2006, 59 patients with thin melanomas (28 females and 31 males; mean age: 58.7 years) underwent lymphatic mapping and sentinel lymph node biopsy. The mean Breslow thickness was 0.60 mm (range: 0.24-1 mm). Tumour ulceration was present in 2 patients (3.4%) and histological regression in 45 (76.3%). Sentinel lymph node metastases were detected in 2 of 59 patients (3.4%), but only one patient with a positive sentinel lymph node exhibited histological regression of his tumour. Therefore, the sentinel lymph node positivity rate in thin regressing melanomas was 2.2%. Literature data and our experience suggest that tumour regression is not a predictor of sentinel lymph node metastasis in patients with thin melanomas, and therefore does not justify the routine use of lymphatic mapping and sentinel lymph node biopsy in this melanoma setting.

Sentinel lymph node biopsy in patients with thin melanomas.

The aim of the present study is to report our experience with lymphatic mapping (LM) and sentinel lymph node biopsy (SLNB) in a selected group of patients with thin primary cutaneous melanomas. Fifty patients (22 females and 28 males; mean age, 57.8 years; range, 30-77 years) with a mean tumor thickness of 0.63 mm (range, 0.24-1.00 mm) underwent LM/SLNB. Twenty-eight (56%) of them had Clark level II, 20 (40%) had Clark level III, and two (4%) had Clark level IV. Tumor ulceration was present in two patients (4%) and histological regression in 35 patients (70%). Sentinel lymph node (SLN) metastases occurred in two of 50 patients (4%). The first case was a 0.88-mm thick, Clark level III, non-ulcerated superficial spreading melanoma of the trunk, without any regression. The second case was a 0.95-mm thick, Clark level IV, non-ulcerated superficial spreading melanoma of the neck, with regression. Both patients were disease-free 76 and 50 months after the SLNB procedure and followed complete lymph node dissection, respectively. The patients with negative SLN were disease-free after a median follow up of 44 months (mean, 43.2; range, 15-84 months). Published data and our experience suggest that LM/SLNB is not routinely indicated for melanomas less than 0.75 mm. Our results confirmed the accuracy of the new American Joint Committee on Cancer/International Union Against Cancer criteria, in which SLNB is required for thin melanomas less than 1.0 mm when they have ulceration or Clark level IV and V invasion.

Lymphatic mapping and sentinel lymph node biopsy in the management of primary cutaneous melanoma: report of a single-centre experience.

AIMS AND BACKGROUND: Lymphatic mapping and sentinel lymph node biopsy provide important prognostic data in patients with early stage melanoma and are crucial in guiding the management of the tumor. We report our experience with lymphatic mapping and sentinel lymph node biopsy in a group of patients with primary cutaneous melanoma and discuss recent concepts and controversies on its use. PATIENTS AND METHODS: A total of 111 patients with stage I-II AJCC primary cutaneous melanoma underwent lymphatic mapping and sentinel lymph node biopsy from December 1999 through December 2004 using a standardized technique of preoperative lymphoscintigraphy and biopsy guided by blue dye injection in addition to a hand-held gamma probe. After removal, sentinel lymph nodes were submitted to serial sectioning and permanent preparations for histological and immunohistochemical examination. Complete lymph node dissection was performed only in patients with tumor-positive sentinel lymph nodes. RESULTS: Sentinel lymph nodes were identified and removed in all patients (detection rate of 100%), and metastases were found in 17 cases (15.3%). The incidence of metastasis in sentinel lymph nodes was 2.1%, 15.9%, 35.2%, and 41.6% for melanomas < or 1.0, 1.01-2.0, 2.01-4.0, and > 4.0 mm in thickness, respectively. Complete lymph node dissection was performed in 15 of 17 patients with positive sentinel lymph nodes, and metastases in non-sentinel lymph nodes were detected in only 2 cases (11.7%). Recurrences were more frequently observed in patients with a positive than in those with negative sentinel lymph node (41.1% vs. 5.3% at a median follow-up of 31.5 months, P < 0.001). The false-negative rate was 2.1%. CONCLUSIONS: Our study confirms that lymphatic mapping and sentinel lymph node biopsy allow accurate staging and yield relevant prognostic information in patients with early stage melanoma.

Dynamic magnetic resonance of the wrist in psoriatic arthritis reveals imaging patterns similar to those of rheumatoid arthritis.

This dynamic magnetic resonance imaging (MRI) study is concerned with a prospective evaluation of wrist synovitis in patients with psoriatic arthritis (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy controls. Fifteen consecutive patients with PsA, 49 consecutive patients with RA, 30 RA patients matched for disease severity with those with PsA, and 8 healthy controls were studied. MRI was performed with a low-field (0.2T), extremity-dedicated machine. After an intravenous bolus injection of gadolinium-diethylenetriaminepentaacetic acid, 20 consecutive fast spin-echo axial images of the wrist were obtained every 18 s. The enhancement ratio was calculated both as rate of early enhancement (REE), which shows the slope of the curve of contrast uptake per second during the first 55 s, and as relative enhancement (RE), which indicates the steady state of enhancement. The REE was 1.0 +/- 0.6 in patients with PsA, 1.6 +/- 0.7 in consecutive patients with RA, and 0.1 +/- 0.1 in controls (p <0.001). The RE was 87.1 +/- 39.2 in patients with PsA, 125.8 +/- 48.0 in consecutive RA patients, and 15.5 +/- 19.2 in controls (p <0.001). However, the same figures in matched RA patients were 1.3 +/- 0.7 and 107.3 +/- 48.2, respectively (not significant in comparison with PsA). Rheumatoid-like PsA and oligoarticular PsA did not differ from each other in terms of synovial enhancement. Dynamic MRI shows the same pattern of synovitis in patients with PsA and RA when the two groups are matched for disease severity. This technique cannot be used to differentiate PsA from RA. However, REE and RE were significantly higher in PsA than in normal controls, with only one instance of overlap between values found for the two groups.

Dynamic gadolinium-enhanced magnetic resonance imaging of the wrist in patients with rheumatoid arthritis can discriminate active from inactive disease.

OBJECTIVE: To determine the efficacy of dynamic gadolinium-enhanced magnetic resonance imaging (MRI) of the wrist in the evaluation of disease activity in patients with rheumatoid arthritis (RA). METHODS: Thirty-six patients with RA (with different degrees of disease activity) and 5 healthy controls were studied. MRI was performed with a low-field (0.2T), extremity-dedicated machine. After an intravenous bolus injection of gadolinium-diethylenetriamine pentaacetic acid, 20 consecutive fast spin-echo images of 3 slices of the wrist were obtained every 18 seconds. RESULTS: The curves of synovial membrane enhancement identified the following 2 groups: controls and RA patients in remission, and RA patients with active or intermediately active disease. Both the rate of early enhancement (REE) and relative enhancement (RE) were significantly higher in patients with active RA than in those with inactive RA and controls. The REE and RE were significantly correlated with the number of swollen joints (P < 0.00001 and P = 0.003, respectively), the number of tender joints (P < 0.00001 and P = 0.004, respectively), the Ritchie index (P = 0.0002 for both REE and RE), the Disease Activity Score (P = 0.0004 and P = 0.0008, respectively), the Health Assessment Questionnaire (HAQ) (P = 0.0002 and P = 0.0007, respectively), early morning stiffness (P = 0.001 and P = 0.009, respectively), the C-reactive protein level (P = 0.015 and P = 0.03, respectively), the erythrocyte sedimentation rate (P = 0.03, RE only), and alpha2 globulins (P = 0.036 and P = 0.028, respectively). CONCLUSION: Our data support use of dynamic MRI for discriminating active from inactive RA. Enhancement curves are associated not only with laboratory and clinical indicators of inflammation, but also with the HAQ, a relevant predictor of RA functional outcome. This technique can be repeated frequently and is an excellent candidate for the ideal method for the followup of patients with RA.