Sigrid Whiteside

The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women

Intermittent energy restriction may result in greater improvements in insulin sensitivity and weight control than daily energy restriction (DER). We tested two intermittent energy and carbohydrate restriction (IECR) regimens, including one which allowed ad libitum protein and fat (IECR+PF). Overweight women (n 115) aged 20 and 69 years with a family history of breast cancer were randomised to an overall 25 % energy restriction, either as an IECR (2500-2717 kJ/d, < 40 g carbohydrate/d for 2 d/week) or a 25 % DER (approximately 6000 kJ/d for 7 d/week) or an IECR+PF for a 3-month weight-loss period and 1 month of weight maintenance (IECR or IECR+PF for 1 d/week). Insulin resistance reduced with the IECR diets (mean - 0·34 (95% CI - 0·66, - 0·02) units) and the IECR+PF diet (mean - 0·38 (95% CI - 0·75, - 0·01) units). Reductions with the IECR diets were significantly greater compared with the DER diet (mean 0·2 (95% CI - 0·19, 0·66) μU/unit, P= 0·02). Both IECR groups had greater reductions in body fat compared with the DER group (IECR: mean - 3·7 (95% CI - 2·5, - 4·9) kg, P= 0·007; IECR+PF: mean - 3·7 (95% CI - 2·8, - 4·7) kg, P= 0·019; DER: mean - 2·0 (95% CI - 1·0, 3·0) kg). During the weight maintenance phase, 1 d of IECR or IECR+PF per week maintained the reductions in insulin resistance and weight. In the short term, IECR is superior to DER with respect to improved insulin sensitivity and body fat reduction. Longer-term studies into the safety and effectiveness of IECR diets are warranted.

Angiogenesis is induced and wound size is reduced by electrical stimulation in an acute wound healing model in human skin

Angiogenesis is critical for wound healing. Insufficient angiogenesis can result in impaired wound healing and chronic wound formation. Electrical stimulation (ES) has been shown to enhance angiogenesis. We previously showed that ES enhanced angiogenesis in acute wounds at one time point (day 14). The aim of this study was to further evaluate the role of ES in affecting angiogenesis during the acute phase of cutaneous wound healing over multiple time points. We compared the angiogenic response to wounding in 40 healthy volunteers (divided into two groups and randomised), treated with ES (post-ES) and compared them to secondary intention wound healing (control). Biopsy time points monitored were days 0, 3, 7, 10, 14. Objective non-invasive measures and H&E analysis were performed in addition to immunohistochemistry (IHC) and Western blotting (WB). Wound volume was significantly reduced on D7, 10 and 14 post-ES (p = 0.003, p = 0.002, p<0.001 respectively), surface area was reduced on days 10 (p = 0.001) and 14 (p<0.001) and wound diameter reduced on days 10 (p = 0.009) and 14 (p = 0.002). Blood flow increased significantly post-ES on D10 (p = 0.002) and 14 (p = 0.001). Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase (p<0.05) in VEGF-A expression by ES treatment on days 7, 10 and 14 (39%, 27% and 35% respectively) and PLGF expression on days 3 and 7 (40% on both days), compared to normal healing. Similarly, WB demonstrated an increase (p<0.05) in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% (p>0.05) on day 14 in VEGF-A expression post-ES compared to controls. Furthermore, organisation of granulation tissue was improved on day 14 post-ES. This randomised controlled trial has shown that ES enhanced wound healing by reduced wound dimensions and increased VEGF-A and PLGF expression in acute cutaneous wounds, which further substantiates the role of ES in up-regulating angiogenesis as observed over multiple time points. This therapeutic approach may have potential application for clinical management of delayed and chronic wounds.

Neurological aspects of human parvovirus B19 infection: a systematic review

Parvovirus B19 has been linked with various clinical syndromes including neurological manifestations. However, its role in the latter remains not completely understood. Although the last 10 years witnessed a surge of case reports on B19‐associated neurological aspects, the literature data remains scattered and heterogeneous, and epidemiological information on the incidence of B19‐associated neurological aspects cannot be accurately extrapolated. The aim of this review is to identify the characteristics of cases of B19‐associated neurological manifestations. A computerized systematic review of existing literature concerning cases of B19‐related neurological aspects revealed 89 articles describing 129 patients; 79 (61.2%) were associated with CNS manifestations, 41 (31.8%) were associated with peripheral nervous system manifestations, and 9 (7.0%) were linked with myalgic encephalomyelitis. The majority of the cases (50/129) had encephalitis. Clinical characteristic features of these cases were analyzed, and possible pathological mechanisms were also described. In conclusion, B19 should be included in differential diagnosis of encephalitic syndromes of unknown etiology in all age groups. Diagnosis should rely on investigation of anti‐B19 IgM antibodies and detection of B19 DNA in serum or CSF. Treatment of severe cases might benefit from a combined regime of intravenous immunoglobulins and steroids. To confirm these outcomes, goal‐targeted studies are recommended to exactly identify epidemiological scenarios and explore potential pathogenic mechanisms of these complications. Performing retrospective and prospective and multicenter studies concerning B19 and neurological aspects in general, and B19 and encephalitic syndromes in particular, are required.

Electrical stimulation increases blood flow and haemoglobin levels in acute cutaneous wounds without affecting wound closure time: evidenced by non‐invasive assessment of temporal biopsy wounds in human volunteers

Recent studies highlighted the beneficial effects of a novel electrical stimulation waveform, the degenerate wave (DW), on skin fibroblasts and symptomatic skin scarring. However, no study to date has investigated the role of DW on acute cutaneous wounds. Therefore, we evaluated this in a trial using a temporal punch biopsy model. Twenty healthy volunteers had a biopsy performed on day 0 (left arm) and day 14 (right arm). On day 14, DW was applied. Participants were randomised into two groups. Objective non‐invasive assessments were performed on days 0, 7, 14, 60 and 90 using spectrophotometric intracutaneous analysis and full‐field laser perfusion imaging. There were statistically significant increases in mean flux on day 14 (P = 0.027) in the post‐DW arm. Haemoglobin levels increased on day 7 for the post‐DW arm compared to without DW (P = 0.088). Differences in melanin levels were higher post‐DW on the left arm between randomised groups on day 90 (P = 0.033). Haemoglobin levels in the vascular ring increased significantly from day 7 to 90 (P < 0.001 for post‐DW and without DW arms). This study, for the first time, shows that DW increases blood flow and haemoglobin levels in acute healing wounds without affecting wound closure time and may have potential application in enhancing acute cutaneous healing.

Optical coherence tomography: a reliable alternative to invasive histological assessment of acute wound healing in human skin?

Gold‐standard assessment of acute wound healing has traditionally been through histological analysis of biopsied tissue. However, this process is invasive with recognized side‐effects. Optical coherence tomography (OCT) is a noninvasive technique generating high‐resolution real‐time images of cutaneous architecture.

The Impact of the SAGE & THYME Foundation Level Workshop on Factors Influencing Communication Skills in Health Care Professionals

Introduction: The “SAGE & THYME Foundation Level Workshop” delivers evidence‐based communication skills training to 30 health care workers in 3 hours. It teaches a structured approach (the SAGE & THYME model) to discuss patient/carer concerns. The aim of this study was to determine whether the workshop had a positive outcome on factors that influence communication skills. Methods: The study had a pragmatic, mixed methods design. Workshops were run in an acute hospital. One hundred seventy health care workers completed questionnaires pre‐ and post‐workshop; 141 were sent follow‐up questionnaires at 2 weeks and 2 months; and 9 were filmed talking to a simulated patient pre‐ and post‐workshop. Results: From pre‐ to post‐workshop, there was a significant increase in knowledge (p < 0.001), self‐efficacy (p < 0.001), and outcome expectancy (p < 0.001). An experts rating of behavior with the simulated patient also significantly increased after the training (p = 0.011). Motivation to use the training, and the perceived usefulness of the SAGE & THYME model, were high post‐workshop. There was a poor response rate in the follow‐up period; hence, the quantitative data are not reported. The qualitative data are described, however, as they give an insight into the impact of the training on staff and their patients. Discussion: The SAGE & THYME Foundation Level Workshop significantly increases communication skills knowledge, self‐efficacy, and outcome expectancy of hospital health care workers who are predominantly white, female, nursing, or nonclinical staff. This suggests that the workshop may have a positive impact on some factors influencing communication skills in this group.

A comparison of image interpretation times in full field digital mammography and digital breast tomosynthesis

Digital Breast Tomosynthesis (DBT) provides three-dimensional images of the breast that enable radiologists to discern whether densities are due to overlapping structures or lesions. To aid assessment of the cost-effectiveness of DBT for screening, we have compared the time taken to interpret DBT images and the corresponding two-dimensional Full Field Digital Mammography (FFDM) images. Four Consultant Radiologists experienced in reading FFDM images (4 years 8 months to 8 years) with training in DBT interpretation but more limited experience (137-407 cases in the past 6 months) were timed reading between 24 and 32 two view FFDM and DBT cases. The images were of women recalled from screening for further assessment and women under surveillance because of a family history of breast cancer. FFDM images were read before DBT, according to local practice. The median time for readers to interpret FFDM images was 17.0 seconds, with an interquartile range of 12.3-23.6 seconds. For DBT, the median time was 66.0 seconds, and the interquartile range was 51.1-80.5 seconds. The difference was statistically significant (p<0.001). Reading times were significantly longer in family history clinics (p<0.01). Although it took approximately four times as long to interpret DBT than FFDM images, the cases were more complex than would be expected for routine screening, and with higher mammographic density. The readers were relatively inexperienced in DBT interpretation and may increase their speed over time. The difference in times between clinics may be due to increased throughput at assessment, or decreased density.

Same task, same observers, different values: the problem with visual assessment of breast density

The proportion of radio-opaque fibroglandular tissue in a mammographic image of the breast is a strong and modifiable risk factor for breast cancer. Subjective, area-based estimates made by expert observers provide a simple and efficient way of measuring breast density within a screening programme, but the degree of variability may render the reliable identification of women at increased risk impossible. This study examines the repeatability of visual assessment of percent breast density by expert observers. Five consultant radiologists and two breast physicians, all with at least two years’ experience in mammographic density assessment, were presented with 100 digital mammogram cases for which they had estimated density at least 12 months previously. Estimates of percent density were made for each mammographic view and recorded on a printed visual analogue scale. The level of agreement between the two sets of estimates was assessed graphically using Bland-Altman plots. All but one observer had a mean difference of less than 6 percentage points, while the largest mean difference was 14.66 percentage points. The narrowest 95% limits of agreement for the differences were -11.15 to 17.35 and the widest were -13.95 to 40.43. Coefficients of repeatability ranged from 14.40 to 38.60. Although visual assessment of breast density has been shown to be strongly associated with cancer risk, the lack of agreement shown here between repeat assessments of the same images by the same observers questions the reliability of using visual assessment to identify women at high risk or to detect moderate changes in breast density over time.

Ethnic variation in volumetric breast density

Volumetric breast density was determined using QuantraTM (Hologic) in 1356 women undergoing routine breast screening. Self-reported ethnicity, age, HRT use, weight and height were also available. 1038 women declared themselves to be White (British or Irish), 71 Black, 77 Asian, 91 Jewish, 31 Mixed Race and 48 Other European. Most of the Jewish group were Ashkenazi, a group in which there is a high probability of genetic susceptibility to breast cancer. Women with screen-detected or previous cancers were excluded. The only significant difference in breast density found between ethnic groups was between the Jewish women and women of White (British or Irish) ethnicity, where mean volumetric densities were 19.61% and 16.89% respectively (p=0.012), however this difference is only of borderline significance (p=0.053) once adjustments are made for age, Body Mass Index (BMI) and use of Hormone Replacement Therapy (HRT). The Jewish women had on average a lower BMI and were more likely to have used HRT.

Abstract P2-02-01: Randomised controlled trial of stereotactic 11g vacuum-assisted or core biopsy for diagnosis and management of malignant microcalcification

Background Vaccum-assisted biopsy (VAB) is claimed to improve diagnosis of malignant microcalcification (MM) and prevent underestimation of invasive component compared to stereotactic core biopsy (SCNB) 14g biopsies. VAB is also reported to reduce requirement for further surgical procedures versus SCNB. Methods In a randomised controlled trial, we compared both techniques in the firstline diagnosis of MM and subsequent surgical management in two UK Breast Screening Units. Patients with MM were identified and gave written informed consent to the study before randomisation 1:1 to SCNB or VAB. Exclusions included bleeding diathesis or significant comorbidity preventing surgery. SCNB was performed by advanced radiography practitioners and VAB by experienced radiologists under local anaesthesia. Quality of life was assessed using EORTC QLQ-BR23 questionnaire: Pre-biopsy, 2, 6, and 12 months post-randomisation. The primary objective compared the final pathological diagnosis with the initial biopsy (VAB or SCNB) and required 110 patients to be randomised to show a 25% improvement in diagnostic accuracy with VAB compared to SCNB with a 90% power. Results Three quarters of MM investigated was less than 15mm in size. Overall 787 women were investigated for eligibility. 476 did not meet the inclusion criteria, 82 declined to participate and 100 met exclusion criteria. In total, 129 women were randomised. Both groups were evenly matched for age 57.2 years (range 47-75) and lesion size but VAB took longer (p There was an 84% diagnostic accuracy of SCNB which precluded any effect on surgical outcome. Both groups had significant Quality of Life (QOL) falls in Global Health (p Conclusion SCNB has equal accuracy as VAB in the firstline diagnosis of malignant microcalcification. Devicor provided the equipment to Dr S.B. and Prof. N.B., to do this study. Citation Format: Sara M Bundred, Jin Zhou, Anthony Maxwell, Sigrid Whiteside, Julie Morris, Janicke Harake, Nigel J Bundred. Randomised controlled trial of stereotactic 11g vacuum-assisted or core biopsy for diagnosis and management of malignant microcalcification [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-02-01.