Pharmacodynamic effects following co-administration of cannabinoids and opioids: A scoping review of human experimental studies.

BACKGROUND: Cannabinoids are increasingly used in the management of chronic pain. Although analgesic potential has been demonstrated, cannabinoids interact with a range of bodily functions that are also influenced by chronic pain medications, including opioids. OBJECTIVE: We performed a scoping review of literature on the pharmacodynamic effects following co-administration of cannabinoids and opioids. METHODS: We systematically searched EMBASE, PubMed, and PsycINFO for studies that experimentally investigated the co-effects of cannabinoids and opioids in human-subjects. Available evidence was summarized by clinical population and organ system. A risk of bias assessment was performed. RESULTS: A total of sixteen studies met inclusion criteria. Study populations included patients with chronic non-cancer and cancer pain on long-term opioid regimens and healthy young adults without prior exposure to opioids who were subject to experimental nociceptive stimuli. Commonly administered cannabinoid agents included Δ9-tetrahydrocannabinol and/or cannabidiol. Co-administration of cannabinoids and opioids did not consistently improve pain outcomes; however, sleep and mood benefits were observed in chronic pain patients. Increased somnolence, memory and attention impairment, dizziness, gait disturbance, and nauseousness and vomiting were noted with co-administration of cannabinoids and opioids. Cardiorespiratory effects following co-administration appeared to vary according to duration of exposure, population type, and prior exposure to cannabinoids and opioids. CONCLUSIONS: The available evidence directly investigating the pharmacodynamic effects following co-administration of cannabinoids and opioids for non-analgesic outcomes is scarce and suffers from a lack of methodological reporting. As such, further research in this area with comprehensive methodologic reporting is warranted.

Sea-surface temperature pattern effects have slowed global warming and biased warming-based constraints on climate sensitivity.

The observed rate of global warming since the 1970s has been proposed as a strong constraint on equilibrium climate sensitivity (ECS) and transient climate response (TCR)-key metrics of the global climate response to greenhouse-gas forcing. Using CMIP5/6 models, we show that the inter-model relationship between warming and these climate sensitivity metrics (the basis for the constraint) arises from a similarity in transient and equilibrium warming patterns within the models, producing an effective climate sensitivity (EffCS) governing recent warming that is comparable to the value of ECS governing long-term warming under CO[Formula: see text] forcing. However, CMIP5/6 historical simulations do not reproduce observed warming patterns. When driven by observed patterns, even high ECS models produce low EffCS values consistent with the observed global warming rate. The inability of CMIP5/6 models to reproduce observed warming patterns thus results in a bias in the modeled relationship between recent global warming and climate sensitivity. Correcting for this bias means that observed warming is consistent with wide ranges of ECS and TCR extending to higher values than previously recognized. These findings are corroborated by energy balance model simulations and coupled model (CESM1-CAM5) simulations that better replicate observed patterns via tropospheric wind nudging or Antarctic meltwater fluxes. Because CMIP5/6 models fail to simulate observed warming patterns, proposed warming-based constraints on ECS, TCR, and projected global warming are biased low. The results reinforce recent findings that the unique pattern of observed warming has slowed global-mean warming over recent decades and that how the pattern will evolve in the future represents a major source of uncertainty in climate projections.

A new conceptual model of global ocean heat uptake.

We formulate a new conceptual model, named "MT2", to describe global ocean heat uptake, as simulated by atmosphere-ocean general circulation models (AOGCMs) forced by increasing atmospheric CO2, as a function of global-mean surface temperature change T and the strength of the Atlantic meridional overturning circulation (AMOC, M). MT2 has two routes whereby heat reaches the deep ocean. On the basis of circumstantial evidence, we hypothetically identify these routes as low- and high-latitude. In low latitudes, which dominate the global-mean energy balance, heat uptake is temperature-driven and described by the two-layer model, with global-mean T as the temperature change of the upper layer. In high latitudes, a proportion p (about 14%) of the forcing is taken up along isopycnals, mostly in the Southern Ocean, nearly like a passive tracer, and unrelated to T. Because the proportion p depends linearly on the AMOC strength in the unperturbed climate, we hypothesise that high-latitude heat uptake and the AMOC are both affected by some characteristic of the unperturbed global ocean state, possibly related to stratification. MT2 can explain several relationships among AOGCM projections, some found in this work, others previously reported: ∙ Ocean heat uptake efficiency correlates strongly with the AMOC. ∙ Global ocean heat uptake is not correlated with the AMOC. ∙ Transient climate response (TCR) is anticorrelated with the AMOC. ∙ T projected for the late twenty-first century under high-forcing scenarios correlates more strongly with the effective climate sensitivity than with the TCR.

Participatory evaluation of the process of co-producing resources for the public on data science and artificial intelligence.

BACKGROUND: The growth of data science and artificial intelligence offers novel healthcare applications and research possibilities. Patients should be able to make informed choices about using healthcare. Therefore, they must be provided with lay information about new technology. A team consisting of academic researchers, health professionals, and public contributors collaboratively co-designed and co-developed the new resource offering that information. In this paper, we evaluate this novel approach to co-production. METHODS: We used participatory evaluation to understand the co-production process. This consisted of creative approaches and reflexivity over three stages. Firstly, everyone had an opportunity to participate in three online training sessions. The first one focused on the aims of evaluation, the second on photovoice (that included practical training on using photos as metaphors), and the third on being reflective (recognising one's biases and perspectives during analysis). During the second stage, using photovoice, everyone took photos that symbolised their experiences of being involved in the project. This included a session with a professional photographer. At the last stage, we met in person and, using data collected from photovoice, built the mandala as a representation of a joint experience of the project. This stage was supported by professional artists who summarised the mandala in the illustration. RESULTS: The mandala is the artistic presentation of the findings from the evaluation. It is a shared journey between everyone involved. We divided it into six related layers. Starting from inside layers present the following experiences (1) public contributors had space to build confidence in a new topic, (2) relationships between individuals and within the project, (3) working remotely during the COVID-19 pandemic, (4) motivation that influenced people to become involved in this particular piece of work, (5) requirements that co-production needs to be inclusive and accessible to everyone, (6) expectations towards data science and artificial intelligence that researchers should follow to establish public support. CONCLUSIONS: The participatory evaluation suggests that co-production around data science and artificial intelligence can be a meaningful process that is co-owned by everyone involved.

Modern technology offers new treatment options for patients and novel avenues of research. However, there is limited available information in easily understandable language for the public explaining how technology relates to them and could influence their healthcare. The researchers, healthcare professionals and public members worked together collaboratively to address this problem by creating new materials for the public. Our paper explores that project through creative methods. Firstly, everyone involved was offered an opportunity to attend training sessions. Then, people took photos and described them to illustrate to others what is their experience of working together. Finally, we all met to use included photos as building blocks to present a shared experience in the project. Afterwards, the professional artist included it as one circular illustration with six interlinked layers. These layers present everyone's experiences (from inside) (1) is about the opportunity to build confidence in a new topic, (2) relationships with others, (3) working remotely during the pandemic, (4) motivation that influenced people to become involved in this particular piece of work, (5) expectation that the project needs be inclusive and accessible, (6) ethical principles that researchers using new technology should follow. We showed that it is possible for researchers, healthcare professionals and members of the public to feel joint ownership of the project and that working together can be meaningful to everyone.

Energy budget diagnosis of changing climate feedback.

The climate feedback determines how Earth's climate responds to anthropogenic forcing. It is thought to have been more negative in recent decades due to a sea surface temperature "pattern effect," whereby warming is concentrated in the western tropical Pacific, where nonlocal radiative feedbacks are very negative. This phenomenon has however primarily been studied within climate models. We diagnose a pattern effect from historical records as an evolution of the climate feedback over the past five decades. Our analysis assumes a constant rate of change of the climate feedback, which is justified post hoc. We find a decrease in climate feedback by 0.8 ± 0.5 W m-2 K-1 over the past 50 years, corresponding to a reduction in climate sensitivity. Earth system models' climate feedbacks instead increase over this period. Understanding and simulating this historical trend and its future evolution are critical for reliable climate projections.

At the limit? Using operational data to estimate train driver human reliability.

Human reliability analysis plays an important role in the safety assessment and management of rail operations. This paper discusses how the increasing availability of operational data can be used to develop an understanding of train driver reliability. The paper derives human reliability data for two driving tasks, stopping at red signals and controlling speed on approach to buffer stops. In the first of these cases, a tool has been developed that can estimate the number of times a signal is approached at red by trains on the Great Britain (GB) rail network. The tool has been developed using big data techniques and ideas, recording and analysing millions of pieces of data from live operational feeds to update and summarise statistics from thousands of signal locations in GB on a daily basis. The resulting driver reliability data are compared to similar analyses of other train driving tasks. This shows human reliability approaching the currently accepted limits of human performance. It also shows higher error rates amongst freight train drivers than passenger train drivers for these tasks. The paper highlights the importance of understanding the task specific performance limits if further improvements in human reliability are sought. It also provides a practical example of how big data could play an increasingly important role in system error management, whether from the perspective of understanding normal performance and the limits of performance for specific tasks or as the basis for dynamic safety indicators which, if not leading, could at least become closer to real time.

Impact of the national sarcoma guidelines on the prevalence and outcome of inadvertent excisions of soft tissue sarcomas: An observational study from a UK tertiary referral centre.

OBJECTIVES: This study aims to investigate the impact of the national guideline on the prevalence and outcome in patients with soft-tissue sarcoma (STS) who had undergone inadvertent excisions. METHODS: A total of 2336 patients were referred to a tertiary sarcoma centre from six regions (North East, North West, East Midlands, West Midlands, Wales, and South West) in the United Kingdom with a diagnosis of STS between 1996 and 2016, of whom 561 patients (24.0%) had undergone inadvertent excisions. Patients were categorised into two groups of 10-year periods pre and post the National Institute for Health and Clinical Excellence (NICE) guideline implementation in 2006. RESULTS: The proportion of inadvertent excisions decreased after the NICE guideline implementation: 27.2% (pre-NICE) versus 19.8% (post-NICE) (p = 0.001). A substantial regional variation (17.4%-34.5%) in the proportion of inadvertent excisions in the pre-NICE era was reduced in the post-NICE era (14.3%-22.4%). The 5-year disease-specific survival was 77.7% (pre-NICE) versus 75.6% (post-NICE) (p = 0.961) and there was a trend toward lower incidence of local recurrence in the post-NICE era; 13.5% (pre-NICE) versus 10.5% (post-NICE) (p = 0.522). Multivariate analyses revealed that residual tumours in re-resection specimens were independently associated with an increased risk of disease-specific mortality (HR, 3.35; p < 0.001) and local recurrence (HR, 1.99; p = 0.017), which was significantly reduced after the NICE guideline implementation (53.2% versus 42.0%; p = 0.022). CONCLUSIONS: The NICE guideline implementation reduced the proportion of patients with STS who had undergone inadvertent excisions and residual tumour in re-resection specimens, indicating an improved pre-referral management of STSs.

Estimating Ocean Heat Uptake Using Boundary Green's Functions: A Perfect-Model Test of the Method.

Ocean heat uptake is caused by "excess heat" being added to the ocean surface by air-sea fluxes and then carried to depths by ocean transports. One way to estimate excess heat in the ocean is to propagate observed sea surface temperature (SST) anomalies downward using a Green's function (GF) representation of ocean transports. Taking a "perfect-model" approach, we test this GF method using a historical simulation, in which the true excess heat is diagnosed. We derive GFs from two approaches: (a) simulating GFs using idealized tracers, and (b) inferring GFs from simulated CFCs and climatological tracers. In the model world, we find that combining simulated GFs with SST anomalies reconstructs the Indo-Pacific excess heat with a root-mean-square error of 26% for depth-integrated changes; the corresponding number is 34% for inferred GFs. Simulated GFs are inaccurate because they are coarse grained in space and time to reduce computational cost. Inferred GFs are inaccurate because observations are insufficient constraints. Both kinds of GFs neglect the slowdown of the North Atlantic heat uptake as the ocean warms up. SST boundary conditions contain redistributive cooling in the Southern Ocean, which causes an underestimate of heat uptake there. All these errors are of comparable magnitude, and tend to compensate each other partially. Inferred excess heat is not sensitive to: (a) small changes in the shape of prior GFs, or (b) additional constraints from SF6 and bomb 14C.

Regional variation in the survival of patients with a soft-tissue sarcoma of the extremity and trunk wall under a centralized care system : what has been the impact of national policies in the UK?

AIMS: While a centralized system for the care of patients with a sarcoma has been advocated for decades, regional variations in survival remain unclear. The aim of this study was to investigate regional variations in survival and the impact of national policies in patients with a soft-tissue sarcoma (STS) in the UK. METHODS: The study included 1,775 patients with a STS who were referred to a tertiary sarcoma centre. The geographical variations in survival were evaluated according to the periods before and after the issue of guidance by the National Institute for Health and Care Excellence (NICE) in 2006 and the relevant evolution of regional management. RESULTS: There had been a significant difference in survival between patients referred from the North East, North West, East Midlands, West Midlands, South West, and Wales in the pre-NICE era (five-year disease-specific survival (DSS); South West, 74% vs North East, 47% (p = 0.045) or West Midlands, 54% (p = 0.049)), which was most evident for patients with a high-grade STS. However, this variation disappeared in the post-NICE era, in which the overall DSS for high-grade STS improved from 47% to 68% at five years (p < 0.001). Variation in the size of the tumour closely correlated with the variation in DSS, and the overall size of the tumour and incidence of metastasis at the time of diagnosis also decreased after the national policies were issued. CONCLUSION: The survival of patients with a STS improved and regional variation corrected after the introduction of national policies, as a result of a decreasing size of tumour and incidence of metastasis at the time of diagnosis, particularly in patients with a high-grade STS. This highlights the positive impact of national guidelines on regional variation in the presentation, management, and outcome in patients with a STS. Cite this article: Bone Joint J 2021;103-B(9):1541-1549.

Projected land ice contributions to twenty-first-century sea level rise.

The land ice contribution to global mean sea level rise has not yet been predicted1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models2-8, but primarily used previous-generation scenarios9 and climate models10, and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios11,12 using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.

A Daily Diagnostic Multidisciplinary Meeting to Reduce Time to Definitive Diagnosis in the Context of Primary Bone and Soft Tissue Sarcoma.

BACKGROUND AND OBJECTIVES: Cancer services are under increasing pressure to deliver waiting time targets. Our service has seen referral numbers increase to over 3000 per annum, with more than 80% coming from secondary care. In order to deliver a responsive service, the department has introduced a daily diagnostic multidisciplinary meeting (DMDT) with the aim being stratification of resources by directing rapid access to clinics and diagnostics to those felt to be at greatest risk of malignancy at the start of the pathway. It also aimed to improve communication with patients and referrers, consistency in decision making and deliver improved diagnostic turn-around times in a sustainable manner. An evaluation was undertaken to assess whether the introduction of the DMDT has improved the pathway, the primary endpoint being a reduction in time to definitive diagnosis (TTDD). Secondary endpoints included measurements of efficiency and whether there has been a reduction in variation in practice. METHODS: Retrospective access to a prospective database over a 1-month period before (2015) and after (2018) the intervention. RESULTS: The introduction of the DMDT has led to a reduction in TTDD (7 days). The service also has an added benefit in reducing average total patient miles travelled over the course of diagnosis by 22.68 miles. CONCLUSION: The introduction of a diagnostic MDT at the start of the pathway does lead to an improvement in service efficiency and a reduction in TTDD.

How Are Indeterminate Pulmonary Nodules at Diagnosis Associated with Survival in Patients with High-Grade Osteosarcoma?

BACKGROUND: Pulmonary metastases are a poor prognostic factor in patients with osteosarcoma; however, the clinical significance of subcentimeter lung nodules and whether they represent a tumor is not fully known. Because the clinician is faced with decisions regarding biopsy, resection, or observation of lung nodules and the potential impact they have on decisions about resection of the primary tumor, this remains an area of uncertainty in patient treatment. Surgical management of the primary tumor is tailored to prognosis, and it is unclear how aggressively patients with indeterminate pulmonary nodules (IPNs), defined as nodules smaller than 1 cm at presentation, should be treated. There is a clear need to better understand the clinical importance of these nodules. QUESTIONS/PURPOSES: (1) What percentage of patients with high-grade osteosarcoma and spindle cell sarcoma of bone have IPNs at diagnosis? (2) Are IPNs at diagnosis associated with worse metastasis-free and overall survival? (3) Are there any clinical or radiologic factors associated with worse overall survival in patients with IPN? METHODS: Between 2008 and 2016, 484 patients with a first presentation of osteosarcoma or spindle cell sarcoma of bone were retrospectively identified from an institutional database. Patients with the following were excluded: treatment at another institution (6%, 27 of 484), death related to complications of neoadjuvant chemotherapy (1%, 3 of 484), Grade 1 or 2 on final pathology (4%, 21 of 484) and lack of staging chest CT available for review (0.4%, 2 of 484). All patients with abnormalities on their staging chest CT underwent imaging re-review by a senior radiology consultant and were divided into three groups for comparison: no metastases (70%, 302 of 431), IPN (16%, 68 of 431), and metastases (14%, 61 of 431) at the time of diagnosis. A random subset of CT scans was reviewed by a senior radiology registrar and there was very good agreement between the two reviewers (κ = 0.88). Demographic and oncologic variables as well as treatment details and clinical course were gleaned from a longitudinally maintained institutional database. The three groups did not differ with regard to age, gender, subtype, presence of pathological fracture, tumor site, or chemotherapy-induced necrosis. They differed according to local control strategy and tumor size, with a larger proportion of patients in the metastases group presenting with larger tumor size and undergoing nonoperative treatment. There was no differential loss to follow-up among the three groups. Two percent (6 of 302) of patients with no metastases, no patients with IPN, and 2% (1 of 61) of patients with metastases were lost to follow-up at 1 year postdiagnosis but were not known to have died. Individual treatment decisions were determined as part of a multidisciplinary conference, but in general, patients without obvious metastases received (neo)adjuvant chemotherapy and surgical resection for local control. Patients in the no metastases and IPN groups did not differ in local control strategy. For patients in the IPN group, staging CT images were inspected for IPN characteristics including number, distribution, size, location, presence of mineralization, and shape. Subsequent chest CT images were examined by the same radiologist to reevaluate known nodules for interval change in size and to identify the presence of new nodules. A random subset of chest CT scans were re-reviewed by a senior radiology resident (κ = 0.62). The association of demographic and oncologic variables with metastasis-free and overall survival was first explored using the Kaplan-Meier method (log-rank test) in univariable analyses. All variables that were statistically significant (p < 0.05) in univariable analyses were entered into Cox regression multivariable analyses. RESULTS: Following re-review of staging chest CTs, IPNs were found in 16% (68 of 431) of patients, while an additional 14% (61 of 431) of patients had lung metastases (parenchymal nodules 10 mm or larger). After controlling for potential confounding variables like local control strategy, tumor size, and chemotherapy-induced necrosis, we found that the presence of an IPN was associated with worse overall survival and a higher incidence of metastases (hazard ratio 1.9 [95% CI 1.3 to 2.8]; p = 0.001 and HR 3.6 [95% CI 2.5 to 5.2]; p < 0.001, respectively). Two-year overall survival for patients with no metastases, IPN, or metastases was 83% [95% CI 78 to 87], 65% [95% CI 52 to 75] and 45% [95% CI 32 to 57], respectively (p = 0.001). In 74% (50 of 68) of patients with IPNs, it became apparent that they were true metastatic lesions at a median of 5.3 months. Eighty-six percent (43 of 50) of these patients had disease progression by 2 years after diagnosis. In multivariable analysis, local control strategy and tumor subtype correlated with overall survival for patients with IPNs. Patients who were treated nonoperatively and who had a secondary sarcoma had worse outcomes (HR 3.6 [95% CI 1.5 to 8.3]; p = 0.003 and HR 3.4 [95% CI 1.1 to 10.0]; p = 0.03). The presence of nodule mineralization was associated with improved overall survival in the univariable analysis (87% [95% CI 39 to 98] versus 57% [95% CI 43 to 69]; p = 0.008), however, because we could not control for other factors in a multivariable analysis, the relationship between mineralization and survival could not be determined. We were unable to detect an association between any other nodule radiologic features and survival. CONCLUSION: The findings show that the presence of IPNs at diagnosis is associated with poorer survival of affected patients compared with those with normal staging chest CTs. IPNs noted at presentation in patients with high-grade osteosarcoma and spindle cell sarcoma of bone should be discussed with the patient and be considered when making treatment decisions. Further work is required to elucidate how the nodules should be managed. LEVEL OF EVIDENCE: Level III, prognostic study.

Venous thromboembolism in orthopaedic oncology.

AIMS: Malignancy and surgery are risk factors for venous thromboembolism (VTE). We undertook a systematic review of the literature concerning the prophylactic management of VTE in orthopaedic oncology patients. METHODS: MEDLINE (PubMed), EMBASE (Ovid), Cochrane, and CINAHL databases were searched focusing on VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), bleeding, or wound complication rates. RESULTS: In all, 17 studies published from 1998 to 2018 met the inclusion criteria for the systematic review. The mean incidence of all VTE events in orthopaedic oncology patients was 10.7% (1.1% to 27.7%). The rate of PE was 2.4% (0.1% to 10.6%) while the rate of lethal PE was 0.6% (0.0% to 4.3%). The overall rate of DVT was 8.8% (1.1% to 22.3%) and the rate of symptomatic DVT was 2.9% (0.0% to 6.2%). From the studies that screened all patients prior to hospital discharge, the rate of asymptomatic DVT was 10.9% (2.0% to 20.2%). The most common risk factors identified for VTE were endoprosthetic replacements, hip and pelvic resections, presence of metastases, surgical procedures taking longer than three hours, and patients having chemotherapy. Mean incidence of VTE with and without chemical prophylaxis was 7.9% (1.1% to 21.8%) and 8.7% (2.0% to 23.4%; p = 0.11), respectively. No difference in the incidence of bleeding or wound complications between prophylaxis groups was reported. CONCLUSION: Current evidence is limited to guide clinicians. It is our consensus opinion, based upon logic and deduction, that all patients be considered for both mechanical and chemical VTE prophylaxis, particularly in high-risk patients (pelvic or hip resections, prosthetic reconstruction, malignant diagnosis, presence of metastases, or surgical procedures longer than three hours). Additionally, the surgeon must determine, in each patient, if the risk of haemorrhage outweighs the risk of VTE. No individual pharmacological agent has been identified as being superior in the prevention of VTE events. Cite this article: Bone Joint J 2020;102-B(12)1743:-1751.

Comorbidities and Pregnancy Do Not Affect Local Recurrence in Patients With Giant Cell Tumour of Bone.

This study evaluates the relationship between pregnancy, comorbid conditions and giant cell tumour of bone. Furthermore, it examines if pregnancy and comorbid conditions affect the outcome following treatment for this tumour. A multi-centre retrospective review was conducted of consecutive patients with a confirmed histological diagnosis of giant cell tumour of bone between June 2012 and May 2017. A total of 195 patients were identified from two centres. Of these, 168 patients were treated with curative intent and had more than six months follow-up. Data were collected on pregnancy status, comorbid conditions, site of disease, surgical management and local recurrence rates. Statistical analysis included the Fisher exact test and Kaplan-Meier survival analysis. There were 72 females of childbearing age, of which 15 (21%) were currently pregnant or had been pregnant within the last six months. The pregnancy rate is higher than the highest reported pregnancy rate over the last 10 years (8.4%; Fisher test, p = 0.033). Women were more likely to have a comorbid condition than men (Fisher test, p < 0.002) and had a higher rate of autoimmune disease than the normal population (p = 0.015). Men were older than women (Wilcoxon test, p = 0.046) and had less risk of local recurrence (logrank test, p = 0.014). Pregnancy or comorbid conditions did not increase the local recurrence rate. Predictors for local recurrence included location in the distal radius (logrank test, p < 0.001), intralesional treatment (logrank test, p = 0.008) and age less than 40 (logrank test, p = 0.043). In conclusion, giant cell tumour of bone is more common in pregnant females and patients with immune disease. Comorbidities and pregnancy do not affect the local recurrence rate. Male patients over 40 years of age have a lower risk of local recurrence, and patients with disease in the distal radius have a high risk of recurrence.

The role of radiotherapy in the treatment of superficial soft-tissue sarcomas.

AIMS: The existing clinical guidelines do not describe a clear indication for adjuvant radiotherapy (RT) in the treatment of superficial soft tissue sarcomas (STSs). We aimed to determine the efficacy of adjuvant RT for superficial STSs. METHODS: We retrospectively studied 304 patients with superficial STS of the limbs and trunk who underwent surgical resection at a tertiary sarcoma centre. The efficacy of RT was investigated according to the tumour size and grade: group 1, ≤ 5 cm, low grade; group 2, ≤ 5cm, high grade; group 3, > 5 cm, low grade; group 4, > 5 cm, high grade. RESULTS: The five- and ten-year local recurrence-free survival (LRFS) for all patients was 88% and 81%, respectively. While the efficacy of adjuvant RT was not proven in local control of all patients (five-year LRFS; RT+, 90% versus RT-, 83%; p = 0.074), the LRFS was significantly improved by adjuvant RT in group 2 (five-year LRFS; RT+, 96% versus RT-, 82%; p = 0.019), and group 4 (five-year LRFS; RT+, 87% versus RT-, 73%; p = 0.027). In groups 2 and 4, adjuvant RT significantly reduced the LR risk if the resection margin was clear but less than 5 mm; the LR rate was 7% with adjuvant RT compared with 26% with surgery alone (p = 0.003). There was no statistical relationship with the use of adjuvant RT and survival in every group. CONCLUSION: Adjuvant RT reduces the risk of local recurrence in patients with superficial high-grade STS regardless of tumour size, especially when resection margin is less than 5 mm. Cite this article: Bone Joint J 2020;102-B(8):1088-1094.

Radiological Features of Giant Cell Tumours of Bone.

Introduction The aim of this study was to evaluate radiological measurements to establish the origin of giant cell tumours of bone. Methods A multi-centre retrospective review was conducted of patients with histologically confirmed giant cell tumours of bone. Images were analysed to estimate the centre of the tumour. Measured from the joint line, the ratio between the distance of the centre of the tumour and the physeal scar was calculated. Results Ninety-five patients were included in the study. Two observers found the tumour to be arising from the metaphyseal area in 94% - 97% of the cases. There was good agreement between the measurements of observers (interclass correlation coefficient 0.71). Conclusion  Giant cell tumours of bone appear to be arising from the metaphyseal region.

Secondary chondrosarcoma arising from osteochondroma: outcomes and prognostic factors.

AIMS: The aim of this study was to report the outcomes of patients who underwent definitive surgery for secondary chondrosarcomas arising from osteochondromas. PATIENTS AND METHODS: A total of 51 patients with secondary chondrosarcomas occurring from osteochondromas were reviewed. Median age was 36 years (interquartile range (IQR) 15 to 82). Median follow-up was 6.9 years (IQR 2.8 to 10.6). The pelvis was the most commonly affected site (59%). Histological grades were grade I in 35 (69%), grade II in 13 (25%), and grade III in three patients (6%). RESULTS: Preoperative biopsy histology correctly predicted the final histological grade in 27% of patients. The ten-year disease-specific survival (DSS) for all patients was 89.4%. Local recurrence occurred in 15 patients (29%), more commonly in pelvic tumours (37%) compared with limb tumours (19%). Four patients with pelvic tumours died from progression of local recurrence. No patient with limb tumours died of disease. Wide/radical margin was associated with improved local recurrence-free survival (p = 0.032) and local recurrence was associated with worse DSS (p = 0.005). CONCLUSION: We recommend that a secondary chondrosarcoma arising from osteochondroma of the pelvis is resected with wide/radical resection margins. The balance between the morbidity of surgery and risk of local recurrence needs to be considered in patients with limb secondary chondrosarcomas. Cite this article: Bone Joint J 2019;101-B:1313-1320.

Patient Perceptions of the Impact of Treatment (Surgery and Radiotherapy) for Soft Tissue Sarcoma.

BACKGROUND AND OBJECTIVES: Treatment for soft tissue sarcoma (STS) is challenging for patients. This study aimed to gain an in-depth understanding of patients' experiences of STS treatment, including whether the sequence of treatment (preoperative or postoperative radiotherapy) influences patient perceptions. METHODS: Face-to-face semi-structured interviews were conducted with nineteen patients who had been treated for STS with surgery and radiotherapy between 2011 and 2016. Topics discussed included perceptions of treatment, social support, and coping mechanisms. Qualitative, inductive, thematic analysis was conducted and structured using the Framework approach. RESULTS: Treatment sequence itself did not appear to cause concern, but uncertainty regarding treatment and side effects could negatively impact participants. Social relationships and individual coping strategies influenced participants' experiences of treatment. CONCLUSIONS: Participants' perceptions of the treatment process varied; the experience was highly individual. It is important to ensure individual psychosocial and information needs are met. In particular, the removal of uncertainty regarding treatment is important in supporting patients undergoing treatment for soft tissue sarcoma.