Safety of emergency, elective and day case operating during the winter period at East Suffolk and North Essex NHS Foundation Trust: lessons from the outcomes of 4,254 surgical patients from the first COVID-19 wave.

BACKGROUND: There is limited evidence on perioperative outcomes of surgical patients during the COVID-19 pandemic to inform continued operating into the winter period. METHODS: We retrospectively analysed the rate of 30-day COVID-19 transmission and mortality of all surgical patients in the three hospitals in our trust in the East of England during the first lockdown in March 2020. All patients who underwent a swab were swabbed on or 24 hours prior to admission. RESULTS: There were 4,254 patients and an overall 30-day mortality of 0.99%. The excess surgical mortality in our region was 0.29%. There were 39 patients who were COVID-19 positive within 30 days of admission, 12 of whom died. All 12 were emergency admissions with a length of stay longer than 24 hours. There were three deaths among those who underwent day case surgery, one of whom was COVID-19 negative, and the other two were not swabbed but not suspected to have COVID-19. There were two COVID-19 positive elective cases and none in day case elective or emergency surgery. There were no COVID-19 positive deaths in elective or day case surgery. CONCLUSIONS: There was a low rate of COVID-19 transmission and mortality in elective and day case operations. Our data have allowed us to guide patients in the consent process and provided the evidence base to restart elective and day case operating with precautions and regular review. A number of regions will be similarly affected and should perform a review of their data for the winter period and beyond.

High efficiency photomodulators for millimeter wave and THz radiation.

Photomodulators for mm-wave and THz radiation are an essential component for many imaging and signal processing applications. While a myriad of schemes have been devised to enhance photomodulation by enhancing the light-matter interaction, there has been less focus on the photoconductive materials themselves, which are often the limiting factor. Here, we present an approach to increase the photomodulation efficiency of silicon by orders of magnitude, using post treatment of off-the-shelf silicon wafers. The increase in efficiency removes the need for bulky and costly amplified laser sources, and creates the potential for compact and cost-effective modulators for real-world applications. By passivating the surfaces of long bulk-lifetime silicon wafers with Al2O3, the recombination of the photoexcited carriers at the surfaces is mostly eliminated. This results in vastly longer excess carrier lifetimes (up to ~50 ms), with corresponding increases in photoconductivity. The resulting modulators are highly efficient, with the transmission through them being reduced from ~90% to <10% over a narrow frequency band with a continuous wave excitation intensity of just 10 Wm-2, whilst modulation factors of greater than 80% can be achieved over a broad band with similar intensities. We also discuss the limitations of such long-lifetime modulators for applications where the switching speed or spatial resolution of a modulator may be critical.

Measurement of concentrations of four chemical ultraviolet filters in human breast tissue at serial locations across the breast.

The human population is widely exposed to benzophenone-3 (BP-3), octylmethoxycinnamate (OMC), 4-methylbenzilidenecamphor (4-MBC) and homosalate from their use in consumer goods to absorb ultraviolet (UV) light. Their oestrogenic activity and presence in human milk suggest a potential to influence breast cancer development. In this study, high-performance liquid chromatography-tandem mass spectrometry was used to measure concentrations of these UV filters in human breast tissue from three serial locations across the breast from 40 women undergoing mastectomy for primary breast cancer. One or more of these UV filters were quantifiable in 101 of 120 (84%) of the tissue samples and at least one breast region for 38 of 40 women. BP-3 was measured in 83 of 120 (69%) tissue samples and at least one breast region for 33 of 40 women (range 0-26.0 ng g-1 tissue). OMC was measured in 89 of 120 (74%) tissue samples and at least one breast region for 33 of 40 women (range 0-58.7 ng g-1 tissue). 4-MBC was measured in 15 of 120 (13%) tissue samples and at least one breast region for seven of 40 women (range 0-25.6 ng g-1 tissue). Homosalate was not detected in any sample. Spearman's analyses showed significant positive correlations between concentrations of BP-3 and OMC in each of the three breast regions. For ethical reasons cancerous tissue was not available, but as the location of the cancer was known, Mann-Whitney U-tests investigated any link between chemical concentration and whether a tumour was present in that region or not. For the lateral region, more BP-3 was measured when a tumour was present (P = .007) and for OMC the P value was .061. For seven (of 40) women with measurable 4-MBC, six of seven had measurable 4-MBC at the site of the tumour.

Attitudes to contralateral risk reducing mastectomy among breast and plastic surgeons in England.

INTRODUCTION: Rates of contralateral risk reducing mastectomy (CRRM) are rising despite a paucity of data to support this practice. Surgeons work as part of the multidisciplinary team (MDT). They may counsel women on these requests without the benefit of established guidelines or agreed protocol. This study assessed the practices and perceptions of breast and plastic surgeons in England on CRRM. METHODS: A postal questionnaire was sent to 455 breast and 364 plastic surgeons practising in England. Basic demographics, trends in CRRM, risk assessment, role of the MDT and knowledge base were assessed. RESULTS: The response rate among breast surgeons was 48.3% (220/455) and 12.6% (46/364) among plastic surgeons. Nearly half (44%) of the respondents felt there had been an increase in rates of CRRM over the last three years. Seventy-one per cent of those surveyed performed 1-5 CRRMs annually while sixteen per cent did not perform this procedure at all. A third (32%) of respondents correctly quoted their patients an annual risk of 0.5-0.7%. Funding was refused in 4% of cases and 43% of the surgeons felt that in the future they would have to apply to relevant clinical commissioning groups. Over half (58%) of all respondents reported that decisions for CRRM are always discussed in the MDT meeting but 6% stated that these cases are never discussed by the MDT. BRCA mutation was perceived as the main risk factor for contralateral breast cancer by 81% of respondents. Surgeons felt that women requested CRRM mainly to alleviate anxiety. The next most common reasons were carriage of BRCA mutation and a desire to have reconstructions match. CONCLUSIONS: A wide variation of surgical practices and perceptions exist in assessing women for CRRM. Guidelines to standardise practices are required.

The Manchester guidelines for contralateral risk-reducing mastectomy.

BACKGROUND: Rates of contralateral risk-reducing mastectomy (CRRM) are rising, despite a decreasing global incidence of contralateral breast cancer. Reasons for requesting this procedure are complex, and we have previously shown a variable practice amongst breast and plastic surgeons in England. We propose a protocol, based on a published systematic review, a national UK survey and the Manchester experience of CRRM. METHODS: We reviewed the literature for risk factors for contralateral breast cancer and have devised a 5-step process that includes history taking, calculating contralateral breast cancer risk, cooling off period/counselling, multi-disciplinary assessment and consent. Members of the multi-disciplinary team included the breast surgeon, plastic surgeon and geneticist, who formulated guidelines. RESULTS: A simple formula to calculate the life-time risk of contralateral breast cancer has been devised. This allows stratification of breast cancer patients into different risk-groups: low, above average, moderate and high risk. Recommendations vary according to different risk groups. CONCLUSION: These guidelines are a useful tool for clinicians counselling women requesting CRRM. Risk assessment is mandatory in this group of patients, and our formula allows evidence-based recommendations to be made.

Contralateral risk-reducing mastectomy: review of risk factors and risk-reducing strategies.

Rates of contralateral risk-reducing mastectomy have increased substantially over the last decade. Surgical oncologists are often in the frontline, dealing with requests for this procedure. This paper reviews the current evidence base regarding contralateral breast cancer, assesses the various risk-reducing strategies, and evaluates the cost-effectiveness of contralateral risk-reducing mastectomy.

Paediatric supracondylar humeral fractures: epidemiology, mechanisms and incidence during school holidays.

PURPOSE: The purpose of this study was to investigate the epidemiology of paediatric patients sustaining supracondylar humeral fractures, to identify common mechanisms of injury and to corroborate the anecdotal evidence that fractures occur more frequently during school holidays. METHODS: All paediatric patients who presented to the accident and emergency department with a supracondylar distal humerus fracture over the 3-year period from 1 July 2008 to 30 June 2011 were included in the study. Data were collected from the electronic medical records and radiology picture archiving and communication system (PACS) regarding age at injury, sex, Gartland type, date of injury, mechanism and management. The dates of all school holidays during the study period were obtained from the local education authority website. RESULTS: A total of 159 patients were identified, with a median age of 6 years 1 month (range 1 year to 14 years 4 months); 53 % of patients were male. The 155 extension-type injuries comprised 46, 28 and 26 % Gartland I, II and III fractures, respectively. Sixty-five patients (41 %) were treated operatively. Six patients had either neurological and/or vascular complications; however, none had any long-term neurological compromise and none required vascular surgical intervention. The mechanism of injury was recorded in 118 cases, the majority (37 %) of which were sustained during falls from play equipment. Among the patients, 115 were of school age. The weekly incidence during school holidays was significantly higher than that during term-time (1.16 vs. 0.60, p = 0.0005). CONCLUSIONS: This study demonstrates the epidemiology of paediatric supracondylar fractures managed at a district general hospital over a 3-year-period. This work supports the long-standing anecdotal evidence that play equipment carries a high risk of injury and that the incidence of supracondylar fractures is significantly higher during school holidays.

Combined dysfunctions of immune cells predict nosocomial infection in critically ill patients.

BACKGROUND: Nosocomial infection occurs commonly in intensive care units (ICUs). Although critical illness is associated with immune activation, the prevalence of nosocomial infections suggests concomitant immune suppression. This study examined the temporal occurrence of immune dysfunction across three immune cell types, and their relationship with the development of nosocomial infection. METHODS: A prospective observational cohort study was undertaken in a teaching hospital general ICU. Critically ill patients were recruited and underwent serial examination of immune status, namely percentage regulatory T-cells (Tregs), monocyte deactivation (by expression) and neutrophil dysfunction (by CD88 expression). The occurrence of nosocomial infection was determined using pre-defined, objective criteria. RESULTS: Ninety-six patients were recruited, of whom 95 had data available for analysis. Relative to healthy controls, percentage Tregs were elevated 6-10 days after admission, while monocyte HLA-DR and neutrophil CD88 showed broader depression across time points measured. Thirty-three patients (35%) developed nosocomial infection, and patients developing nosocomial infection showed significantly greater immune dysfunction by the measures used. Tregs and neutrophil dysfunction remained significantly predictive of infection in a Cox hazards model correcting for time effects and clinical confounders {hazard ratio (HR) 2.4 [95% confidence interval (CI) 1.1-5.4] and 6.9 (95% CI 1.6-30), respectively, P=0.001}. Cumulative immune dysfunction resulted in a progressive risk of infection, rising from no cases in patients with no dysfunction to 75% of patients with dysfunction of all three cell types (P=0.0004). CONCLUSIONS: Dysfunctions of T-cells, monocytes, and neutrophils predict acquisition of nosocomial infection, and combine additively to stratify risk of nosocomial infection in the critically ill.

Comparing the performance of six human papillomavirus tests in a screening population.

BACKGROUND: Several new assays have been developed for high-risk HPV testing of cervical samples; we compare six HPV tests in a screening population. METHODS: Residual material from liquid-based PreservCyt samples was assayed. Four tests (Hybrid Capture 2, Cobas, Abbott and Becton-Dickinson (BD)) measured HPV DNA while two used RNA (APTIMA and NorChip). RESULTS: Positivity rates ranged from 13.4 to 16.3% for the DNA-based tests with a significantly lower positivity rate for the Abbott assay. The Gen-Probe APTIMA assay was positive in 10.3% of women, which was significantly lower than all the DNA tests; the NorChip PreTect HPV-Proofer test was much lower at 5.2%. 40 CIN2+ cases were identified, of which 19 were CIN3+. All CIN3+ cases were HPV positive by all tests except for one, which was negative by the Abbott assay and five which were negative by the NorChip test. CONCLUSION: All HPV tests except NorChip showed high sensitivity for high-grade lesions positive by cytology, suggesting co-testing is unnecessary when using HPV tests. Positivity rates in cytology-negative specimens were similar for the DNA-based tests, but lower for the APTIMA test suggesting this maintains the high sensitivity of DNA tests, but with better specificity.

Should all twins and multiple births undergo ultrasound examination for developmental dysplasia of the hip?: A retrospective study of 990 multiple births.

Twins are often considered to be at an increased risk of developmental dysplasia of the hip (DDH); we therefore investigated whether multiple births have a higher incidence of DDH, and if selective ultrasound scanning should be considered for these infants.We reviewed our records of all live births between 1 January 2004 and 31 December 2008 and included 25 246 single and 990 multiple births.Multiple births did not have a significantly higher incidence of DDH compared with single births (0.0030 vs 0.0023, p = 0.8939). Of the 990 multiple births, 267 had neonatal ultrasound scans and one case of DDH was diagnosed and treated successfully with a Pavlik harness. There were two late-presenting cases at eight and 14 months of age, neither of whom had risk factors for DDH and consequently had not had a neonatal scan. Whereas selective ultrasound scanning of multiple births would have led to earlier detection and treatment of the late-presenting cases, they did not have a significantly higher incidence of DDH compared with single births.We conclude that being a twin or triplet in itself is not a risk factor for DDH and that selective ultrasound scanning is not indicated for this population.

Cost minimisation analysis of using acellular dermal matrix (Strattice™) for breast reconstruction compared with standard techniques.

BACKGROUND: We performed a cost analysis (using UK 2011/12 NHS tariffs as a proxy for cost) comparing immediate breast reconstruction using the new one-stage technique of acellular dermal matrix (Strattice™) with implant versus the standard alternative techniques of tissue expander (TE)/implant as a two-stage procedure and latissimus dorsi (LD) flap reconstruction. METHODS: Clinical report data were collected for operative time, length of stay, outpatient procedures, and number of elective and emergency admissions in our first consecutive 24 patients undergoing one-stage Strattice reconstruction. Total cost to the NHS based on tariff, assuming top-up payments to cover Strattice acquisition costs, was assessed and compared to the two historical control groups matched on key variables. RESULTS: Eleven patients having unilateral Strattice reconstruction were compared to 10 having TE/implant reconstruction and 10 having LD flap and implant reconstruction. Thirteen patients having bilateral Strattice reconstruction were compared to 12 having bilateral TE/implant reconstruction. Total costs were: unilateral Strattice, £3685; unilateral TE, £4985; unilateral LD and implant, £6321; bilateral TE, £5478; and bilateral Strattice, £6771. CONCLUSIONS: The cost analysis shows a financial advantage of using acellular dermal matrix (Strattice) in unilateral breast reconstruction versus alternative procedures. The reimbursement system in England (Payment by Results) is based on disease-related groups similar to that of many countries across Europe and tariffs are based on reported hospital costs, making this analysis of relevance in other countries.

Pulmonary and systemic effects of mononuclear leukapheresis.

BACKGROUND AND OBJECTIVES: There is increasing evidence that monocytes play a key role in the pathogenesis of acute lung inflammation. Mononuclear cell (MNC) leukapheresis can be used to remove large numbers of monocytes from circulating blood; however, the detailed characteristics of monocyte subpopulations removed by MNC leukapheresis, and the biological effects on the lung, remain incompletely defined. MATERIAL AND METHODS: Six healthy male volunteers underwent MNC leukapheresis of four total blood volumes. Blood was collected at 0, 2, 4, 6, 8 and 24 h; bronchoscopy with bronchoalveolar lavage (BAL) was performed at 8-9 h. Multiparameter flow cytometry was used to identify subpopulations of monocytes in blood and monocyte-like cells in BAL fluid. RESULTS: A median of 5·57×10(9) monocytes were retrieved. Blood monocyte counts indicated that the circulating blood monocyte pool was actively replenished during leukapheresis and subsequently contained a greater proportion of classical (CD14(++) CD16(-)) monocytes. A particular subpopulation of monocyte-like cells, reminiscent of classical monocytes, was also prominent in BAL fluid after leukapheresis. CONCLUSION: Mononuclear cell leukapheresis was safe. The greater proportion of classical monocytes present in blood after MNC leukapheresis may be clinically significant. MNC leukapheresis also appears to affect the proportion of monocyte-like cells in the lung; however, we found no evidence that leukapheresis has a clinically important pro-inflammatory effect in the human lung.

Measurement of paraben concentrations in human breast tissue at serial locations across the breast from axilla to sternum.

The concentrations of five esters of p-hydroxybenzoic acid (parabens) were measured using HPLC-MS/MS at four serial locations across the human breast from axilla to sternum using human breast tissue collected from 40 mastectomies for primary breast cancer in England between 2005 and 2008. One or more paraben esters were quantifiable in 158/160 (99%) of the tissue samples and in 96/160 (60%) all five esters were measured. Variation was notable with respect to individual paraben esters, location within one breast and similar locations in different breasts. Overall median values in nanograms per gram tissue for the 160 tissue samples were highest for n-propylparaben [16.8 (range 0-2052.7)] and methylparaben [16.6 (range 0-5102.9)]; levels were lower for n-butylparaben [5.8 (range 0-95.4)], ethylparaben [3.4 (range 0-499.7)] and isobutylparaben 2.1 (range 0-802.9). The overall median value for total paraben was 85.5 ng g(-1) tissue (range 0-5134.5). The source of the paraben cannot be identified, but paraben was measured in the 7/40 patients who reported never having used underarm cosmetics in their lifetime. No correlations were found between paraben concentrations and age of patient (37-91 years), length of breast feeding (0-23 months), tumour location or tumour oestrogen receptor content. In view of the disproportionate incidence of breast cancer in the upper outer quadrant, paraben concentrations were compared across the four regions of the breast: n-propylparaben was found at significantly higher levels in the axilla than mid (P = 0.004 Wilcoxon matched pairs) or medial (P = 0.021 Wilcoxon matched pairs) regions (P = 0.010 Friedman ANOVA).

HPV self-sampling as an alternative strategy in non-attenders for cervical screening - a randomised controlled trial.

BACKGROUND: A randomised trial to ascertain whether women who do not attend for cervical screening are more likely to respond to the opportunity to collect a self-sample for human papillomavirus (HPV) testing, or to a further invitation to attend for cervical screening. METHODS: The study was carried out in a Primary Care Trust (PCT) in London between June 2009 and December 2009. In total, 3000 women were randomly selected from persistent non-responders (i.e., who had not responded to at least two invitations to attend for screening). The women were randomised on a 1 : 1 basis to either receive an HPV self-sampling kit or a further invitation to attend for cervical cytology. The main outcome measures were (1) percentage of women attending for cervical cytology compared with those returning a self-sample HPV test or attending for cytology subsequent to receiving the kit and (2) percentage of those testing positive for HPV who attended further investigation. RESULTS: The total response in the self-sampling group for screening was 10.2%. Of the 1500 women in the control group sent a further invitation for cervical screening, 4.5% attended for cytology screening. This difference is highly statistically significant (P<0.0001). Of the 8 women who tested positive for HPV, 7 attended for a cervical smear and had a concurrent colposcopy. Three of these (43%) had high-grade disease (defined as CIN 2+), with one found to have an invasive cancer (stage 1b) and one CIN 3. CONCLUSIONS: The value of this intervention relies on the detection of high-grade CIN and early stage cancer with a good prognosis. The relatively high yield of abnormalities found is consistent with that expected among a hard to reach and relatively high-risk group of women. Our study suggests that self-sampling could increase participation among non-responders in England, but further work is needed to ascertain whether the low response rate seen here is likely to be representative of the rest of the country. Other studies are needed to investigate the response to self-sampling in different demographic and geographic settings.

Screening younger women with a family history of breast cancer--does early detection improve outcome?

Women with a family history are often offered mammographic surveillance at an earlier age and with greater frequency than those in the National Breast Screening Programme. In this study, we compared the survival of 62 breast cancer patients diagnosed in the context of a family history clinic offering 12-18 monthly mammographic screening with that of 1108 patients of the same age range but having no exposure to screening. We subtracted the expected additional observation time due to lead time from the survival of the screen-detected cases. Survival was significantly better in the family history group with relative hazards of 0.19 (95% CI 0.07-0.52, P<0.001) for breast cancer death and 0.19 (95% CI 0.08-0.43, P<0.001) for disease-free survival. After correcting for lead-time, the relative hazards were 0.24 (95% CI 0.09-0.66, P=0.005) for breast cancer death and 0.25 (95% CI 0.11-0.57, P<0.001) for disease-free survival. These results strongly suggest that screening younger women with a family history of breast cancer leads to improved survival. More precise estimates of the benefit will accrue from further follow-up and other such studies.