Exploring atmospheric optical turbulence: observations across zenith angles.

We present measurements of the atmospheric optical turbulence as a function of zenith angle using two identical instruments, Shack-Hartmann Image Motion Monitors (SHIMMs), to measure atmospheric parameters concurrently. One instrument was pointed near zenith, while the other collected data by tracking a single star until it set and thus sampling zenith angles continuously to the horizon. By comparing these measurements, we can attribute changes in the atmospheric parameters to the changing zenith angle rather than variations in local turbulence conditions. The primary purpose of this experiment is to make comparisons between the measurements of the scintillation index, σ I2, and Fried parameter, r 0, with current theories. In this demonstration, we find that there is a strong agreement between the models and the instrument up until zenith angles of 70∘, above which model and measurements begin to deviate. We discuss various ways in which limitations in models and our instrument may cause these deviations.

Real-world treatment sequencing and survival in previously treated advanced renal cell carcinoma patients receiving nivolumab monotherapy: a UK retrospective cohort study.

BACKGROUND: The CheckMate 025 trial established nivolumab monotherapy as one of the standards of care in previously treated advanced or metastatic renal cell carcinoma (aRCC). However, supporting real-world data is lacking. This study investigated characteristics, treatment sequences and clinical outcomes of patients who received nivolumab monotherapy for previously treated aRCC in the UK. METHODS: This was a retrospective cohort study of aRCC patients treated with nivolumab at second line or later (2L +) at 4 UK oncology centres. Eligible patients commenced nivolumab (index date) between 01 March 2016 and 30 June 2018 (index period). Study data were extracted from medical records using an electronic case report form. Data cut-off (end of follow-up) was 31 May 2019. RESULTS: In total, 151 patients were included with median follow-up of 15.2 months. Mean age was 66.9 years, male preponderance (72.2%), and mostly Eastern Cooperative Oncology Group performance status grade 0-1 (71.5%). Amongst 112 patients with a known International Metastatic RCC Database Consortium score, distribution between favourable, intermediate, and poor risk categories was 20.5%, 53.6%, and 25.9% respectively. The majority of patients (n = 109; 72.2%) received nivolumab at 2L, and these patients had a median overall survival (OS) of 23.0 months [95% confidence interval: 17.2, not reached]. All patients who received nivolumab at 2L had received TKIs at 1L. Amongst the 42 patients (27.8%) who received nivolumab in third line or later (3L +) the median OS was 12.4 months [95% CI: 8.8, 23.2]. The most common reasons for nivolumab discontinuation were disease progression (2L: 61.2%; 3L: 68.8%) and adverse events (2L: 34.7%; 3L: 28.1%). CONCLUSION: This study provides real-world evidence on the characteristics, treatment sequences, and outcomes of aRCC patients who received 2L + nivolumab monotherapy in the UK. Nivolumab-specific survival outcomes were similar to those achieved in the CheckMate 025 trial.

Guideline for the management of hip fractures 2020: Guideline by the Association of Anaesthetists.

We convened a multidisciplinary Working Party on behalf of the Association of Anaesthetists to update the 2011 guidance on the peri-operative management of people with hip fracture. Importantly, these guidelines describe the core aims and principles of peri-operative management, recommending greater standardisation of anaesthetic practice as a component of multidisciplinary care. Although much of the 2011 guidance remains applicable to contemporary practice, new evidence and consensus inform the additional recommendations made in this document. Specific changes to the 2011 guidance relate to analgesia, medicolegal practice, risk assessment, bone cement implantation syndrome and regional review networks. Areas of controversy remain, and we discuss these in further detail, relating to the mode of anaesthesia, surgical delay, blood management and transfusion thresholds, echocardiography, anticoagulant and antiplatelet management and postoperative discharge destination. Finally, these guidelines provide links to supplemental online material that can be used at readers' institutions, key references and UK national guidance about the peri-operative care of people with hip and periprosthetic fractures during the COVID-19 pandemic.

Long-term trends in critical care admissions in Wales*.

As national populations age, demands on critical care services are expected to increase. In many healthcare settings, longitudinal trends indicate rising numbers and proportions of patients admitted to ICU who are older; elsewhere, including some parts of the UK, a decrease has raised concerns with regard to rationing according to age. Our aim was to investigate admission trends in Wales, where critical care capacity has not risen in the last decade. We used the Secure Anonymised Information Linkage Databank to identify and characterise critical care admissions in patients aged ≥ 18 years from 1 January 2008 to 31 December 2017. We categorised 85,629 ICU admissions as youngest (18-64 years), older (65-79 years) and oldest (≥ 80 years). The oldest group accounted for 15% of admissions, the older age group 39% and the youngest group 46%. Relative to the national population, the incidence of admission rates per 10,000 population in the oldest group decreased significantly over the study period from 91.5/10,000 in 2008 to 77.5/10,000 (a relative decrease of 15%), and among the older group from 89.2/10,000 in 2008 to 75.3/10,000 in 2017 (a relative decrease of 16%). We observed significant decreases in admissions with high comorbidity (modified Charlson comorbidity index); increases in the proportion of older patients admitted who were considered 'fit' rather than frail (electronic frailty index); and decreases in admissions with a medical diagnosis. In contrast to other healthcare settings, capacity constraints and surgical imperatives appear to have contributed to a relative exclusion of older patients presenting with acute medical illness.

The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.

BACKGROUND: Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce. OBJECTIVES: To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival. METHODS: We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome. RESULTS: During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90). CONCLUSIONS: Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.

Guidelines for the peri-operative care of people with dementia: Guidelines from the Association of Anaesthetists.

Ageing populations have greater incidences of dementia. People with dementia present for emergency and, increasingly, elective surgery, but are poorly served by the lack of available guidance on their peri-operative management, particularly relating to pharmacological, medico-legal, environmental and attitudinal considerations. These guidelines seek to deliver such guidance, by providing information for peri-operative care providers about dementia pathophysiology, specific difficulties anaesthetising patients with dementia, medication interactions, organisational and medico-legal factors, pre-, intra- and postoperative care considerations, training, sources of further information and care quality improvement tools.

An observational feasibility study of a new anaesthesia drug storage tray.

Drug errors in the anaesthetic domain remain a serious cause of iatrogenic harm. To help reduce this issue, we explored the potential safety impact of using a simple colour-coded tray for anaesthetic drug preparation and storage. Over a six-month period, three different trained researchers observed 30 cases at three NHS Trusts. Ten observations involved standard drug trays in 'normal' practice, and 20 observations, involved 'Rainbow trays' before and after their introduction. We conducted 20 semi-structured interviews immediately after completing the Rainbow tray observation with the anaesthetists involved. All discussions and detailed notes taken were transcribed, qualitatively analysed using line-by-line coding and then synthesised into narrative themes. We found that using standard, single compartment trays enabled quick, cheap, and portable drug preparation and storage, but was linked to potential or actual harmful errors, such as syringe swaps. Rainbow trays were perceived to be easy to use and effective at all three sites, aiding drug identification and separation, and hence likely to reduce drug error and increase patient safety. We have demonstrated that it is feasible to introduce a new colour-coded compartmentalised Rainbow drugs tray into clinical practice at three NHS hospitals in England. Further research is needed into their effect on the prevalence of drug error.

Factors predicting incidence of post-operative delirium in older people following hip fracture surgery: a systematic review and meta-analysis.

OBJECTIVE: Delirium is one of the most common complications following hip fracture surgery in older people. This study identified pre- and peri-operative factors associated with the development of post-operative delirium following hip fracture surgery. METHODS: Published and unpublished literature were searched to identify all evidence reporting variables on patient characteristics, on-admission, intra-operative and post-operative management assessing incident delirium in older people following hip fracture surgery. Pooled odds ratio (OR) and mean difference of those who experienced delirium compared to those who did not were calculated for each variable. Evidence was assessed using the Downs and Black appraisal tool and interpreted using the GRADE approach. RESULTS: A total of 6704 people (2090 people with post-operative delirium) from 32 studies were analysed. There was moderate evidence of nearly a two-times greater probability of post-operative delirium for those aged 80 years and over (OR: 1.77; 95% CI: 1.09, 2.87), whether patients lived in a care institution pre-admission (OR: 2.65; 95% CI: 1.79, 3.92), and a six-times greater probability of developing post-operative delirium with a pre-admission diagnosis of dementia (OR: 6.07, 95% CI: 4.84, 7.62). There was no association with intra-operative variables and probability of delirium. CONCLUSION: Clinicians treating people with a hip fracture should be vigilant towards post-operative delirium if their patients are older, have pre-existing cognitive impairment and poorer overall general health. This is also the case for those who experience post-operative complications such as pneumonia or a urinary tract infection. Copyright © 2017 John Wiley & Sons, Ltd.

Differences in soil micro-eukaryotic communities over soil pH gradients are strongly driven by parasites and saprotrophs.

A recent large-scale assessment of bacterial communities across a range of UK soil types showed that bacterial community structure was strongly determined by soil pH. We analysed a data set of eukaryotic 454 sequencing 18S rDNA from the surveyed samples and showed significant differences in eukaryotic assemblages according to pH class, mostly between low pH and higher pH soils. Soil eukaryote communities (per sample) differed most at the taxonomic rank approximating to order level. Taxonomies assigned with the Protist Ribosomal Reference and the Silva 119 databases were taxonomically inconsistent, mostly due to differing 18S annotations, although general structure and composition according to pH were coherent. A relatively small number of lineages, mostly putative parasitic protists and fungi, drive most differences between pH classes, with weaker contributions from bacterivores and autotrophs. Overall, soil parasites included a large diversity of alveolates, in particular apicomplexans. Phylogenetic analysis of alveolate lineages demonstrates a large diversity of unknown gregarines, novel perkinsids, coccidians, colpodellids and uncharacterized alveolates. Other novel and/or divergent lineages were revealed across the eukaryote tree of life. Our study provides an in-depth taxonomic evaluation of micro-eukaryotic diversity, and reveals novel lineages and insights into their relationships with environmental variables across soil gradients.

Prediction of 30-day mortality after hip fracture surgery by the Nottingham Hip Fracture Score and the Surgical Outcome Risk Tool.

The care of the elderly with hip fractures and their outcomes might be improved with resources targeted by the accurate calculation of risks of mortality and morbidity. We used a multicentre national dataset to evaluate and recalibrate the Nottingham Hip Fracture Score and Surgical Outcome Risk Tool. We split 9,017 hip fracture cases from the Anaesthesia Sprint Audit of Practice into derivation and validation data sets and used logistic regression to derive new model co-efficients for death at 30 postoperative days. The area (95% CI) under the receiver operator characteristic curve of 0.71 (0.67-0.75) indicated acceptable discrimination by the Nottingham Hip Fracture Score and acceptable calibration fit (Hosmer-Lemeshow test), p = 0.23, with a similar discrimination by the Surgical Outcome Risk Tool, 0.70 (0.66-0.74), which was miscalibrated to the observed data, p = 0.001. We recommend that studies test these scores for patients with hip fractures in other countries. We also recommend these models are compared with case-mix adjustment tools used in the UK.

Secondary analysis of outcomes after 11,085 hip fracture operations from the prospective UK Anaesthesia Sprint Audit of Practice (ASAP-2).

We re-analysed prospective data collected by anaesthetists in the Anaesthesia Sprint Audit of Practice (ASAP-1) to describe associations with linked outcome data. Mortality was 165/11,085 (1.5%) 5 days and 563/11,085 (5.1%) 30 days after surgery and was not associated with anaesthetic technique (general vs. spinal, with or without peripheral nerve blockade). The risk of death increased as blood pressure fell: the odds ratio (95% CI) for mortality within five days after surgery was 0.983 (0.973-0.994) for each 5 mmHg intra-operative increment in systolic blood pressure, p = 0.0016, and 0.980 (0.967-0.993) for each mmHg increment in mean pressure, p = 0.0039. The equivalent odds ratios (95% CI) for 30-day mortality were 0.968 (0.951-0.985), p = 0.0003 and 0.976 (0.964-0.988), p = 0.0001, respectively. The lowest systolic blood pressure after intrathecal local anaesthetic relative to before induction was weakly correlated with a higher volume of subarachnoid bupivacaine: r(2) -0.10 and -0.16 for hyperbaric and isobaric bupivacaine, respectively. A mean 20% relative fall in systolic blood pressure correlated with an administered volume of 1.44 ml hyperbaric bupivacaine. Future research should focus on refining standardised anaesthesia towards administering lower doses of spinal (and general) anaesthesia and maintaining normotension.

Corrigendum: Did the addition of concomitant chemotherapy to radiotherapy improve outcomes in hypopharyngeal cancer? A population-based study.

[This corrects the article on p. 266 in vol. 23, PMID: 27536177.].

Did the addition of concomitant chemotherapy to radiotherapy improve outcomes in hypopharyngeal cancer? A population-based study.

BACKGROUND: For oncologists and for patients, no site-specific clinical trial evidence has emerged for the use of concurrent chemotherapy with radiotherapy (ccrt) over radiotherapy (rt) alone for cancer of the hypopharynx (hpc) or for other human papilloma virus-negative head-and-neck cancers. METHODS: This retrospective population-based cohort study using administrative data compared treatments over time (1990-2000 vs. 2000-2010), treatment outcomes, and outcomes over time in 1333 cases of hpc diagnosed in Ontario between January 1990 and December 2010. RESULTS: The incidence of hpc is declining; the use of ccrt that began in 2001 is increasing; and the 3-year overall survival for all patients remains poor at 34.6%. No difference in overall survival was observed in a comparison of patients treated in the decade before ccrt and of patients treated in the decade during the uptake of ccrt. CONCLUSIONS: The addition of ccrt to the armamentarium of treatment options for oncologists treating head-and-neck patients did not improve outcomes for hpc at the population level.

Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma.

BACKGROUND: Tumour-infiltrating lymphocyte (TIL) therapy is showing great promise in the treatment of patients with advanced malignant melanoma. However, the translation of TIL therapy to non-melanoma tumours such as renal cell carcinoma has been less successful with a major constraint being the inability to reproducibly generate TILs from primary and metastatic tumour tissue. METHODS: Primary and metastatic renal cell carcinoma biopsies were subjected to differential tumour disaggregation methods and procedures that stimulate the specific expansion of TILs tested to determine which reliably generated TIL maintained antitumour specificity. RESULTS: Enzymatic or combined enzymatic/mechanical disaggregation resulted in equivalent numbers of TILs being liberated from renal cell carcinoma biopsies. Following mitogenic activation of the isolated TILs with anti-CD3/anti-CD28-coated paramagnetic beads, successful TIL expansion was achieved in 90% of initiated cultures. The frequency of T-cell recognition of autologous tumours was enhanced when tumours were disaggregated using the GentleMACS enzymatic/mechanical system. CONCLUSION: TILs can be consistently produced from renal cell carcinoma biopsies maintaining autologous tumour recognition after expansion in vitro. While the method of disaggregation has little impact on the success of TIL growth, methods that preserve the cell surface architecture facilitate TIL recognition of an autologous tumour, which is important in terms of characterising the functionality of the expanded TIL population.

Safety guideline: reducing the risk from cemented hemiarthroplasty for hip fracture 2015: Association of Anaesthetists of Great Britain and Ireland British Orthopaedic Association British Geriatric Society.

Concise guidelines are presented for the preparation and conduct of anaesthesia and surgery in patients undergoing cemented hemiarthroplasty for hip fracture. The Working Party specifically considered recent publications highlighting complications occurring during the peri-operative period. The advice presented is based on previously published advice and clinical studies.

Peri-operative management of the obese surgical patient 2015: Association of Anaesthetists of Great Britain and Ireland Society for Obesity and Bariatric Anaesthesia.

Guidelines are presented for the organisational and clinical peri-operative management of anaesthesia and surgery for patients who are obese, along with a summary of the problems that obesity may cause peri-operatively. The advice presented is based on previously published advice, clinical studies and expert opinion.

Outcome by mode of anaesthesia for hip fracture surgery. An observational audit of 65 535 patients in a national dataset.

Large observational studies of accurate data can provide similar results to more arduous and expensive randomised controlled trials. In 2012, the National Hip Fracture Database extended its dataset to include 'type of anaesthesia' data fields. We analysed 65 535 patient record sets to determine differences in outcome. Type of anaesthesia was recorded in 59 191 (90%) patients. Omitting patients who received both general and spinal anaesthesia or in whom an uncertain type of anaesthesia was recorded, there was no significant difference in either cumulative five-day (2.8% vs 2.8%, p = 0.991) or 30-day (7.0% vs 7.5%, p = 0.053) mortality between 30 130 patients receiving general anaesthesia and 22 999 patients receiving spinal anaesthesia, even when 30-day mortality was adjusted for age and ASA physical status (p = 0.226). Mortality within 24 hours after surgery was significantly higher among patients receiving cemented compared with uncemented hemiarthroplasty (1.6% vs 1.2%, p = 0.030), suggesting excess early mortality related to bone cement implantation syndrome. If these data are accurate, then either there is no difference in 30-day mortality between general and spinal anaesthesia after hip fracture surgery per se, and therefore future research should focus on how to make both types of anaesthesia safer, or there is a difference, but mortality is not the correct outcome to measure after anaesthesia, and therefore future research should focus on differences between general and spinal anaesthesia. These could include more anaesthesia-sensitive outcomes, such as hypotension, pain, postoperative confusion, respiratory infection and mobilisation.