Trends in incidence and average waiting time for arthroplasty from 1998-2021: an observational study of 282,367 patients from the Scottish arthroplasty project.

BACKGROUND: Current waiting times for arthroplasty are reported as being the worst on record. This is a combination of increasing demand, the COVID-19 pandemic and longer standing shortage of capacity. The Scottish Arthroplasty Project (SAP) is a National Audit that analyses all joint replacements undertaken in the Scottish NHS and Independent Sector. The aim of this study was to investigate the long-term trend in provision and waiting time for lower limb joint replacement surgery. METHODS: All total hip replacements (THR) and total knee replacements (TKR) undertaken in NHS Scotland from 1998 to 2021 were identified. Waiting times data were analysed each year to determine the minimum, maximum, median, mean and standard deviation. RESULTS: In 1998, there were 4,224 THR and 2,898 TKR with mean (range, SD) waiting time of 159.5 days (1-1,685, 119.8) and 182.9 days (1-1,946, 130.1). The minimum waiting times were both in 2013 for 7,612 THR - 78.8 days (0-539, 46) and 7,146 TKR - 79.1 days (0-489, 43.7). The maximum waiting times recorded were in 2021 with 4,070 THR waiting 283.7 days (0-945, 215) and 3,153 TKR waiting 316.8 days (4-1,064, 217). CONCLUSIONS: This is the first robust large-scale national dataset showing trends in incidence and waiting time for THR and TKR over two decades. There was an expansion of activity with a reduction in waiting time, which peaked in 2013, followed by an increase in waiting time with a plateau and modest decline in the number of procedures.

Presence of flavoured electronic nicotine delivery system (ENDS) products in US ENDS advertisements, 2015-2020: a content analysis.

OBJECTIVES: Electronic nicotine delivery systems (ENDS) products come in a variety of flavours (eg, fruit, dessert, menthol). Tobacco advertising has historically used flavours as an advertising tactic, but little is known about flavour type and prevalence in ENDS advertisements. We assess the presence of flavoured ENDS in ads over time, by media outlet (eg, magazines, online) and brand. METHODS: We acquired ENDS ads (N=4546) that first ran between 2015-2017 (n=1685; study 1) and 2018-2020 (n=2861; study 2) in outlets including opt-in emails, direct-to-consumer mail (study 1 only), video (TV and online), radio (study 2 only), static online/mobile (ie, ads without video or moving graphics), social media, outdoor (eg, billboards; study 2 only) and consumer magazines. We coded for presence of flavoured ENDS products and flavour type (eg, fruit, tobacco, menthol) and merged this information with metadata on ad year, outlet and manufacturer/retailer brand. RESULTS: Overall, nearly half (45.5%; n=2067) of ads in our sample featured a flavoured product. Tobacco (59.1%; n=1221), menthol (42.9%; n=887) and fruit (38.6%; n=797) were the most advertised flavours. Over time, the proportion of ads containing tobacco-flavoured and menthol-flavoured ENDS generally decreased before menthol rebounded in 2020. The proportion of ads containing fruit, mint and dessert flavours generally increased over time, with a substantive drop in 2020. We found notable differences in flavoured ENDS advertising by outlet and brand. CONCLUSIONS: The overall presence of flavoured ENDS in our sample of ads remained relatively consistent, with tobacco flavour decreasing over time and some non-tobacco flavours increasing over time until 2020 when the presence decreased.

Super Liquid-repellent Surfaces and 3D Spheroids Growth.

Substrates composition and surface features of materials rule adhesion control of cells to surfaces. As a result, most of the aspects of cell functions, such as spreading, migration, proliferation, and differentiation, can be significantly influenced in biomedical applications. Cell cultures make possible to understand cell biology, tissue morphology, mechanisms of diseases, drug action, and tissue engineering development, among others. Recent techniques related to culturing 3D cell aggregates in the presence of very low wettable surfaces represent an innovative field for in vitro experimentation aimed at more reliable conditions to investigate both tumor and non-tumor cell lines. Matching in particular cell biology to innovative materials, this work reviews the recent literature available on promoting cell aggregates formation strongly influenced by the high surface hydrophobicity. In particular, for spheroid formation, the highest water repellent coatings seem to be required for the significant effectiveness of the process. In this way, 3D cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions.

Mammalian Cell Spheroids on Mixed Organic-Inorganic Superhydrophobic Coating.

Three-dimensional cell culture has become a reliable method for reproducing in vitro cellular growth in more realistic physiological conditions. The surface hydrophobicity strongly influences the promotion of cell aggregate formation. In particular, for spheroid formation, highly water-repellent coatings seem to be required for the significant effects of the process. In this work, surfaces at different wettability have been compared to observe their influence on the growth and promotion of aggregates of representative mammalian cell lines, both tumoral and non-tumoral (3T3, HaCat and MCF-7 cell lines). The effect of increased hydrophobicity from TCPS to agarose hydrogel to mixed organic-inorganic superhydrophobic (SH) coating has been investigated by optical and fluorescence microscopy, and by 3D confocal profilometry, in a time scale of 24 h. The results show the role of less wettable substrates in inducing the formation of spheroid-like cell aggregates at a higher degree of sphericity for the studied cell lines.

On the possibility of using temperature to aid in thyroid nodule investigation.

Thyroid nodules are common, and their investigation is very important to exclude the possibility of cancer. The increase in blood vessels of malignant tumours may be related to local temperature augmentation detectable on the skin surface. The objective of this paper is to evaluate the feasibility of Infrared Thermography for cancer identification. For this purpose, two studies were performed. One used numerical modelling to simulate regional metabolic temperature propagation to evaluate whether a nodule is perceptible on the skin surface. A second study considered thyroid nodule identification by using convolutional neural networks (CNNs). First, variations in nodular size and fat thickness were investigated, showing that the fat layer has an important role in regional heat transfer. In the second study, the training process achieved accuracy of 96% for in-sample and 95% for validation. In the testing phase, 92% accuracy, 100% precision and 80% recall were achieved. Thus, the presented studies suggest the feasibility of using Infrared Thermography with the CNN Artificial Intelligence technique as additional information in the investigation of thyroid nodules for patients without a very thick subcutaneous fat layer.

Aggregation Behavior, Antibacterial Activity and Biocompatibility of Catanionic Assemblies Based on Amino Acid-Derived Surfactants.

The surface activity, aggregates morphology, size and charge characteristics of binary catanionic mixtures containing a cationic amino acid-derived surfactant N(π), N(τ)-bis(methyl)-L-Histidine tetradecyl amide (DMHNHC14) and an anionic surfactant (the lysine-based surfactant Nα-lauroyl-Nεacetyl lysine (C12C3L) or sodium myristate) were investigated for the first time. The cationic surfactant has an acid proton which shows a strong pKa shift irrespective of aggregation. The resulting catanionic mixtures exhibited high surface activity and low critical aggregation concentration as compared with the pure constituents. Catanionic vesicles based on DMHNHC14/sodium myristate showed a monodisperse population of medium-size aggregates and good storage stability. According to Small-Angle X-Ray Scattering (SAXS), the characteristics of the bilayers did not depend strongly on the system composition for the positively charged vesicles. Negatively charged vesicles (cationic surfactant:myristate ratio below 1:2) had similar bilayer composition but tended to aggregate. The DMHNHC14-rich vesicles exhibited good antibacterial activity against Gram-positive bacteria and their bactericidal effectivity declined with the decrease of the cationic surfactant content in the mixtures. The hemolytic activity and cytotoxicity of these catanionic formulations against non-tumoral (3T3, HaCaT) and tumoral (HeLa, A431) cell lines also improved by increasing the ratio of cationic surfactant in the mixture. These results indicate that the biological activity of these systems is mainly governed by the cationic charge density, which can be modulated by changing the cationic/anionic surfactant ratio in the mixtures. Remarkably, the incorporation of cholesterol in those catanionic vesicles reduces their cytotoxicity and increases the safety of future biomedical applications of these systems.

Effect of non-oxidative plasma treatments on the surface properties of poly(p-phenylene terephthalamide) (PPTA) and poly(p-phenylene benzobisoxazole) (PBO) fibres as measured by inverse gas chromatography.

It has been shown in previous works that the interfacial adhesion in PPTA- and PBO-epoxy composites can be improved by modifying the surface properties of these high-performance fibres upon exposure to non-oxidative plasma treatments. In this work, the effects developed on both types of polymer surface were examined as a function of treatment gas nature (He or N2) and exposure time (one or four minutes) using inverse gas chromatography at infinite dilution (IGC). From the adsorption of n-alkanes, it has been proved that non-oxidative plasma treatments led to energetically heterogeneous surfaces in the case of PPTA, and to low-energy surfaces in the case of PBO. Nevertheless, it was proved with the 1-min plasma treatments (either under helium or under nitrogen) that chemical reactivity was enhanced on the PBO surface. Such a behaviour was ascribed to the presence of low-molecular weight oxidized materials. The mechanisms involved in surface activation of PPTA were not equivalent under He or N2 exposure. Nitrogen plasma exposure led to a PPTA surface that is chemically reactive as a result of polarity enhancement. Helium plasma-treated PPTA surface was characterized by the presence of branched arrangements that intensified the number of chemical contacts onto reactive sites. Finally, for both fibre sets, if the purpose is to enhance the chemical surface reactivity, it makes no sense to increase the plasma exposure time from 1 to 4 min.

3D profilometry and cell viability studies for drug response screening.

In vitro tests for assessing cell viability and drug response are widely employed for determining cytotoxicity of drugs, chemicals, or material substrates. These assays have some advantages, such as speed, reduced cost, and potential for automation. However, since these tests are often run with a huge amount of cells, the characteristic properties of a single cell can be masked leading to a lack of the diagnostic features of these assays. Vital processes as proliferation and cell death (either necrosis or apoptosis) are associated to drastic changes of volume and surface analysis techniques like 3D optical scanning profilometry allow noninvasive and nondestructive approach with fast detection and good resolution at nano-microscale. Here, we demonstrate how coupling noninvasive morphological surface analysis techniques with well assessed biochemical methods can help to establish the relationship between the modifications on cellular viability induced by precursors of proliferation and cell death and variations on cell volume induced by these treatments. The proposed approach has demonstrated improved efficiency on the assessment of inductive changes on tumoral cells in comparison to non-tumoral cells upon administration of proliferative nontoxic or cytotoxic substances like chemotherapeutics.

Are national antitobacco campaigns reaching high-risk adolescents? A cross-sectional analysis from PATH Wave 2.

Smoking education and prevention campaigns have had marked success in reducing rates of tobacco use among adolescents, however, disparities in use continue to exist. It is critical to assess if adolescents at risk for tobacco use are being exposed to antitobacco campaigns. We used data from Wave 2 of the Population Assessment of Tobacco and Health Study to assess the relationship between exposure to three antitobacco campaigns and key characteristics related to higher risk of cigarette use using full-sample weights and Poisson regression models with robust variance. Adjusted models identified that exposure to antitobacco campaigns was more common among racial and sexual minority adolescents and adolescents who: reported exposure to tobacco marketing, spent more time using media and had household income greater than $25 000. While some high-risk youth are more likely to report exposure to campaigns, there are some priority groups that are not being reached by current efforts compared with non-priority groups, including youth living in households with income below the poverty line and adolescents who are susceptible to cigarette smoking. Future campaigns should consider targeting these groups specifically in order to reduce tobacco use disparities.

Trainee experience of 'out of hours' surgical working in the UK: A cross-sectional analysis.

BACKGROUND: Changes to working practices and increasing service demand have contributed to low morale amongst UK surgical trainees, with pressures particularly acute 'out of hours' (OOH). Surgeons may be expected to be 'on call' for multiple hospitals, or to provide remote consultations, yet healthcare systems may undermine their professional safety and patient care. This cross-sectional study sought to define the perceptions of UK-based Royal College of Surgeons of Edinburgh (RCSEd) affiliated trainees of OOH surgical care and training. METHODS: The RCSEd Trainees' Committee conducted a design-thinking exercise to produce an online questionnaire. Non-consultant grade RCSEd Members and Fellows were invited to participate. Quantitative data was analysed using descriptive statistics, and qualitative data was coded to identify emergent themes. RESULTS: One hundred and fifty-five surgeons participated. Of those surgeons working in multiple hospitals OOH (n = 16), many did not receive access cards (12[75%]) or site-specific induction (13[81%]), and 8(50%) were not confident in using local electronic investigation and records systems. Only 14/114 (12%) of the surgeons providing remote opinion had access to a consultation record system, and most perceived dissatisfaction with the system. Emergent themes from qualitative data revealed that trainee surgeons desire specific training in OOH working, concerns that OOH work experience is diminishing, and that hospital infrastructure such as IT and communications, rest facilities and catering were inadequate in facilitating safe care. CONCLUSIONS: The participants perceived that the systems supporting delivery of safe surgical care OOH were inadequate. Hospital leaders should ensure that systems minimise risk to staff and patients.

Mammalian cell viability on hydrophobic and superhydrophobic fabrics.

Surface properties like hydrophobicity and morphology of the substrate are essential for cell proliferation affecting its growth, survival and also for its communication with other cells on fabrics. The combination of low surface energy and a specific surface morphology (micro/nano-roughness) leads to significantly less wettable surfaces, known as superhydrophobic characterized by high contact angle above 150° and a very small hysteresis. Such high water repellent coatings feature small area available to be exploited in many applications where interactions with aqueous environment are strongly to be avoided. In this work, the authors have investigated the influence of coating polyester fabric at different degree of hydrophobicity by mixed organic-inorganic coating with moderated to highly water repellence. Depending on the coating composition and structure, the hydrophobicity of the fabric can be finely modulated by an easy-to-prepare method applicable to commercial, low cost fabric substrates providing advanced performance. In vitro experiments have been performed in order to establish the influence of surface modification on adhesion of representative model mammalian cell lines such as 3T3 fibroblasts, HaCaT keratinocytes and HeLa epithelial carcinoma cells. The obtained results suggested that, in addition to the chemistry and morphology of the coating, the characteristics of the substrate are important parameters on the final cell viabilities.

Dual responsive gelatin-based nanoparticles for enhanced 5-fluorouracil efficiency.

The very slow progress in the therapeutic efficacy of the treatment of severe diseases has suggested the use of a growing need for a multidisciplinary approach to the delivery of therapeutics to targets tissues. There has been increasing effort in the design of stimuli-responsive nanomaterials that they will be developed into effective drug delivery vehicles. Most commonly, effective drug delivery is associated with nanomaterial-facilitated accumulation and/or cellular internalization. Recent studies in our lab have demonstrated that gelatin-based NPs can be considered suitable pH responsive devices for the effective intracellular delivery of drugs. Concerning cancer treatment, ligands recognizing tumour-associated antigens expressed on the surface of the tumour cells have been employed. Some of the target structures suitable for tumour targeting belong to integrins which mediate cell adhesion to extracellular matrix and other cells. Interestingly, gelatin chains contain motifs such as RGD sequences that can be recognised by integrins. In this work the inclusion of the anticancer drug 5-fluorouracil (5-FU) on these gelatin-based NPs has been projected. These NPs may provide an opportunity to increase the therapeutic effect using a dual approach by: i) targeting the therapeutic drug to the tumour cells by the action of the naturally occurring RGD-motif on gelatin and ii) minimizing the non-productive trafficking from endosomes to lysosomes by releasing the cargo using the charge reversal approach after cellular internalization. In vitro cytotoxicity experiments of NPs on tumoral and non-tumoral cell lines have reported selectivity indexes higher than 30 demonstrating a great selectivity on the mode of action as a function of the cell line and the imposed compositions.

Recall of preoperative Oxford Hip and Knee Scores one year after arthroplasty is an alternative and reliable technique when used for a cohort of patients.

OBJECTIVES: The primary aim of this study was to assess the reproducibility of the recalled preoperative Oxford Hip Score (OHS) and Oxford Knee Score (OKS) one year following arthroplasty for a cohort of patients. The secondary aim was to assess the reliability of a patient's recollection of their own preoperative OHS and OKS one year following surgery. METHODS: A total of 335 patients (mean age 72.5; 22 to 92; 53.7% female) undergoing total hip arthroplasty (n = 178) and total knee arthroplasty (n = 157) were prospectively assessed. Patients undergoing hip and knee arthroplasty completed an OHS or OKS, respectively, preoperatively and were asked to recall their preoperative condition while completing the same score one year after surgery. RESULTS: A mean difference of 0.04 points (95% confidence intervals (CI) -15.64 to 15.72, p = 0.97) between the actual and the recalled OHS was observed. The mean difference in the OKS was 1.59 points (95% CI -11.57 to 14.75, p = 0.10). There was excellent reliability for the 'average measures' intra-class correlation for both the OHS (r = 0.802) and the OKS (r = 0.772). However, this reliability was diminished for the individuals OHS (r = 0.670) and OKS (r = 0.629) using single measures intra-class correlation. Bland-Altman plots demonstrated wide variation in the individual patient's ability to recall their preoperative score (95% CI ± 16 for OHS, 95% CI ± 13 for OKS). CONCLUSION: Prospective preoperative collection of OHS and OKS remains the benchmark. Using recalled scores one year following hip and knee arthroplasty is an alternative when used to assess a cohort of patients. However, the recall of an individual patient's preoperative score should not be relied upon due to the diminished reliability and wide CI.Cite this article: T. F. M. Yeoman, N. D. Clement, D. Macdonald, M. Moran. Recall of preoperative Oxford Hip and Knee Scores one year after arthroplasty is an alternative and reliable technique when used for a cohort of patients. Bone Joint Res 2018;7:351-356. DOI: 10.1302/2046-3758.75.BJR-2017-0259.R1.

Insurance Companies Fighting the Peer Review Empire without any Validity: the Case for Addiction and Pain Modalities in the face of an American Drug Epidemic.

The United States are amid an opioid overdose epidemic; we are challenged to provide non-addicting/non-pharmacological alternatives to assist in pain attenuation. There are proven strategies available to manage chronic pain effectively without opioids. Utilization review providers for insurance companies often ignore medicine based scientific peer-reviewed studies that warn against the chronic use of opioid medications, as well as the lack of evidence to support long-term use of opioids for pain. This paradigm must change if we are to indeed change the drug-embracing culture in American chronic pain management. A barrier to treatment is pushback on the part of insurance companies especially as it relates to fighting against pain relief alternatives compared to classical analgesic agents. Pain specialists in the U.S., are compelled to find alternative solutions to help pain victims without promoting unwanted tolerance to analgesics and subsequent biological induction of the "addictive brain." It is noteworthy that reward center of the brain plays a crucial role in the modulation of nociception, and that adaptations in dopaminergic circuitry may affect several sensory and affective components of chronic pain syndromes. Possibly knowing a patient's genetic addiction risk score (GARS™) could eliminate guessing as it relates to becoming addicted.

Hair Repigmentation During Immunotherapy Treatment With an Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Agent for Lung Cancer.

Importance: New targeted therapies for cancer have been released in recent years, opening new horizons in the treatment of patients with cancer. However, their related adverse events (AE) are not fully characterized. Hair repigmentation (HR) is a nondescribed effect secondary to anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1 ) therapy for treatment of lung cancer (LC), in opposition to the vitiligo reactions that develop during melanoma treatment. Objective: To describe a new adverse event occurring during anti-PD-1/anti-PD-L1 therapy for LC. Design, Setting, and Participants: A case series from a descriptive observation of 14 patients with HR after anti-PD-1/anti-PD-L1 treatment, recruited between September and December, 2016, who were followed up to detect whether they developed cutaneous AE at the time HR was detected. The patients had all been treated in the dermatology department at Hospital Universitari Germans Trias i Pujol, Badalona, Spain. Main Outcomes and Measures: Clinical observation of HR during anti-PD-1/anti-PD-L1 therapy for LC, proved by comparing old pictures provided by the patients and recent pictures taken during the follow-up. Results: Fourteen patients (13 men and 1 woman; mean age, 64.9 years) receiving anti-PD-1 or anti-PD-L1 therapy for non-small-cell lung cancer (NSCLC) presented hair repigmentation during follow-up. This hair repigmentation consisted in a diffuse darkening of the hair in 13 of 14 patients, or in black patches between white hairs in 1. Thirteen of 14 patients presented a good clinical response to the treatment, with at least stable disease, and only 1 had to stop the therapy after only 4 cycles of treatment owing to a life-threatening progression of the disease. Conclusions and Relevance: We present to our knowledge the first report of hair repigmentation owing to anti-PD-1/anti-PD-L1 therapy for lung cancer in a series of 14 patients. Hair repigmentation may be a good response marker in patients receiving anti-PD1/anti-PD-L1 therapy for LC.

Cellular stress induces TRB3/USP9x-dependent Notch activation in cancer.

Expression of the Notch ligand JAG1 and Notch pathway activation promote poor prognosis, basal-like breast cancer. We have recently shown that the pseudokinase Tribbles homolog 3 (TRB3) regulates JAG1 expression in this malignancy. TRB3 is a stress and metabolic sensor, and here we show that nutrient deprivation or endoplasmic reticulum stress markedly upregulate TRB3, which serves as a scaffold for the deubiquitinase USP9x. USP9x in turn stimulates JAG1 activity through two mechanisms: (1) through TRB3 deubiquitination and stabilization, and (2) through deubiquitination and activation of Mind Bomb 1, an E3 ligase required for JAG1 ubiquitination-mediated endocytosis and Notch activation. These USP9x activities are confined to the signal-sending cell of a cell pair undergoing Notch signaling. We demonstrate that USP9x is required for TRB3 upregulation and Notch activation in response to cellular stress in basal-like breast cancer cells. These data suggest that TRB3 functions as a sensor of tumor microenvironmental stress and together with USP9x induces the cell survival and tumor-promoting activities of Notch. These findings identify a novel mechanism by which cancer cells survive in their hostile environment and provide potential therapeutic targets in breast cancer.

Predicting dissatisfaction following total knee arthroplasty in patients under 55 years of age.

AIMS: Risk of revision following total knee arthroplasty (TKA) is higher in patients under 55 years, but little data are reported regarding non-revision outcomes. This study aims to identify predictors of dissatisfaction in these patients. PATIENTS AND METHODS: We prospectively assessed 177 TKAs (157 consecutive patients, 99 women, mean age 50 years; 17 to 54) from 2008 to 2013. Age, gender, implant, indication, body mass index (BMI), social deprivation, range of movement, Kellgren-Lawrence (KL) grade of osteoarthritis (OA) and prior knee surgery were recorded. Pre- and post-operative Oxford Knee Score (OKS) as well as Short Form-12 physical (PCS) and mental component scores were obtained. Post-operative range of movement, complications and satisfaction were measured at one year. RESULTS: Overall, 44 patients with 44 TKAs (24.9%) under 55 years of age were unsure or dissatisfied with their knee. Significant predictors of dissatisfaction on univariate analysis included: KL grade 1/2 OA (59% dissatisfied), poor pre-operative OKS, complications, poor improvements in PCS and OKS and indication (primary OA 19% dissatisfied, previous meniscectomy 41%, multiply operated 42%, other surgery 29%, BMI > 40 kg/m2 31%, post-traumatic OA 45%, and inflammatory arthropathy 5%). Poor pre-operative OKS, poor improvement in OKS and post-operative stiffness independently predicted dissatisfaction on multivariate analysis. CONCLUSION: Patients receiving TKA younger than 55 years old should be informed about the increased risks of dissatisfaction. Offering TKA in KL 1/2 is questionable, with a dissatisfaction rate of 59%. Cite this article: Bone Joint J 2016;98-B:1625-34.