Aims. Responsiveness to clinically important change is a key feature of any outcome measure. Throughout Europe, health-related quality of life following total knee arthroplasty (TKA) is routinely measured with EuroQol five-dimension (EQ-5D) questionnaires. The Patient-Reported Outcomes Measurement Information System 10-Question Short-Form (PROMIS-10 Global Health) score is a new general heath outcome tool which is thought to offer greater responsiveness. Our aim was to compare these two tools. Patients and Methods. We accessed data from a prospective multicentre cohort study in the United Kingdom, which evaluated outcomes following TKA. The median age of the 721 patients was 69.0 years (interquartile range, 63.3 to 74.6). There was an even division of sex, and approximately half were educated to secondary school level. The preoperative EQ-5D, PROMIS-10, and Oxford Knee Scores (OKS) were available and at three, six, and 12 months postoperatively. Internal responsiveness was assessed by standardized response mean (SRM) and effect size (Cohen’s d). External responsiveness was assessed by correlating change scores of the EQ-5D and PROMIS-10, with the minimal clinically important difference (MCID) of the OKS. Receiver operating characteristic (ROC) curves were used to assess the ability of change scores to discriminate between improved and non-improved patients. Results. All measures showed significant changes between the preoperative score and the various postoperative times (p < 0.001). Most improvement occurred during the first three months, with small but significant changes between three and six months, and no further change between six and 12 months postoperatively. SRM scores for EQ-5D, PROMIS-10, and OKS were large (> 0.8). ROC curves showed that both EQ-5D and PROMIS-10 were able to discriminate between patients who achieved the OKS MCID and those who did not (area under the curve (AUC) of 0.7 to 0.82). Conclusion. The PROMIS-10 physical health tool showed greater responsiveness to change than the EQ-5D, most probably due to the additional questions on physical health parameters that are more susceptible to modification following TKA. The EQ-5D was, however, shown to be sensitive to clinically meaningful change following TKA, and provides the additional ability to calculate health economic utility scores. It is likely, therefore, that EQ-5D will continue to be the global health metric of choice in the United Kingdom. Cite this article: Bone Joint J 2019;101-B:832–837

Chris Lavy is an orthopaedic surgeon in Oxford (UK) who lived and worked in Malawi for ten years. There he helped build an orthopaedic hospital and research unit. He was also one of the founders of COSECSA, the regional college of surgeons for East and Central Africa in 1999.

Aims. To determine whether obesity and malnutrition have a synergistic effect on outcomes from skeletal trauma or elective orthopaedic surgery. Methods. Electronic databases including MEDLINE, Global Health, Embase, Web of Science, ScienceDirect, and PEDRo were searched up to 14 April 2024, as well as conference proceedings and the reference lists of included studies. Studies were appraised using tools according to study design, including the Oxford Levels of Evidence, the Institute of Health Economics case series quality appraisal checklist, and the CLARITY checklist for cohort studies. Studies were eligible if they reported the effects of combined malnutrition and obesity on outcomes from skeletal trauma or elective orthopaedic surgery. Results. A total of eight studies (106,319 patients) were included. These carried moderate to high risk of bias. Combined obesity and malnutrition did not lead to worse outcomes in patients undergoing total shoulder arthroplasty or repair of proximal humeral fractures (two retrospective cohort studies). Three studies (two retrospective cohort studies, one case series) found that malnourishment and obesity had a synergistic effect and led to poor outcomes in total hip or knee arthroplasty, including longer length of stay and higher complication rates. One retrospective cohort study pertaining to posterior lumbar fusion found that malnourished obese patients had higher odds of developing surgical site infection and sepsis, as well as higher odds of requiring a revision procedure. Conclusion. Combined malnutrition and obesity have a synergistic effect and lead to poor outcomes in lower limb procedures. Appropriate preoperative optimization and postoperative care are required to improve outcomes in this group of patients. Cite this article: Bone Joint J 2024;106-B(10):1044–1049

Alcohol hand rubs, endorsed by WHO and NICE guidelines, are integral to modern surgical practices. Our objective was to assess how different scrubbing methods impact overall water usage by the surgical team, shedding light on variations among team members and their environmental implications. Over three consecutive arthroplasty lists spanning a week, water usage during scrubbing was observed for the operating team. Blinding all team members, including the anesthetist, consultant surgeon, orthopaedic registrar, orthopaedic SHO, and scrub nurse, during water usage calculations was implemented. Automated taps, using motion sensors, posed a challenge due to variable water quantity, necessitating water flow calculations per sensor movement. The senior surgeon, with over 20 years of experience, follows a traditional approach, starting with a morning prescrub and using an alcohol tub for each case, except when hands are soiled. We observed a total of 14 cases of lower limb primary arthroplasty. The cumulative water usage for scrubbing by the entire team was 193 liters, yielding a mean of 13.8 liters (±1.85) per case. The anaesthetist demonstrated the most conservative water usage, utilizing a total of 11.85 liters with a mean of 0.84 liters per case. Notably, alcohol rub was employed for half of the observed time, contributing to this efficient use. The senior operating surgeon used a total of 15.6 liters, averaging 1.1 liters per case. In contrast, the SHO and the registrar exhibited the highest water consumption, totaling 121.6 liters and yielding a mean of 5.7 liters per case. The nurses’ collective water usage for scrubbing amounted to 44.8 liters. Adopting alcohol rub, as endorsed by WHO, results in a remarkable 10-fold reduction in water usage, aligning with global health guidelines. This highlights significant potential for resource conservation in surgical procedures, presenting a practical and environmentally conscious approach to surgical scrubbing practices

The global COVID-19 pandemic has resulted in 71 million confirmed global cases and 1.6 million deaths. Hip fractures are a major global health burden with 70 000 admissions per annum in the UK. This multicentre UK study aimed to assess the impact of perioperative COVID-19 status on 30-day and 120-day mortality after a hip fracture. A prospective multicentre study of 10 hospitals in South England comprising eight DGHs and two MTCs treating c.8% of the annual incidence of hip fractures in England was performed. All fragility hip fractures presenting between 1. st. March to 30. th. April 2020 were eligible for inclusion. COVID-19 infection was diagnosed after a positive PCR swab. Expected 30-day mortality was calculated using the Nottingham Hip Fracture Score (NHFS), with non COVID-19 30-day mortality compared against the same study period in 2019. 746 patients were included in this study with 87 (12%) testing positive for COVID-19. Crude 30-day mortality for COVID-19 positive hip fractures was 35% compared to 6% for COVID-19 negative patients, with COVID-19 positive 30-mortality rates being significantly higher than expected based on NHFS alone (RR 3.0, 95% CI 1.57–5.75, p<0.001). There was no significant difference between expected NHFS and actual 2019 and COVID-19 negative hip fracture rates (p>0.05). Overall 120-day mortality was significantly higher for COVID-19 positive (46%) compared to COVID-19 negative (15%) hip fractures (p<0.001). However, mortality rates from 31–120 days were not significantly different despite COVID-19 status (p=0.107). COVID-19 results in significant increases in both 30 and 120-day mortality, above the expected mortality rates when confounding comorbidities are accounted for by the NHFS. However, COVID-19 positive patients who survive beyond 30-days have comparable mortality rates up to 120-days when compared to COVID-19 negative patients. Efforts should therefore be made to mitigate known risks for 30-day mortality such as time to theatre, to improve 30-day mortality rates in COVID-19 positive patients thus increasing the likelihood of long-term survival

Introduction. This analysis aims to provide an update of the Level-IV Partners Arthroplasty Registry (PAR), a quality-improvement initiative and research data repository. Methods. The Harris Joint Registry was founded in 1969 and has since expanded to become the Partners Arthroplasty Registry (PAR). Today, the PAR captures data on total hip and total knee arthroplasties conducted at seven hospitals in Massachusetts. Over time, data has been sourced through independent collection at a single hospital, retrospective sourcing through the Research Patient Data Registry (RPDR), and currently through the Enterprise Data Warehouse (EDW). Various statistical methods analyzed changing trends of care provided to patients across affiliated institutions. PROMs collected in the PAR are the PROMIS Physical Function and Global Health Short Forms, the HOOS and KOOS. The registry is an associate member of ISAR and will incorporate the international implant library. Results. The PAR contains demographic, implant-specifics, and radiographic data for 45,645 primary arthroplasties and 8,400 revision surgeries from 1998 to 2018. The average recorded Charlson Comorbidity Index is 0.98. Average length of stay prior to home or care facility discharge decreased from 5.00 days in 2001 to 3.00 days in 2018. The average 30-day and 90-day mortality rates for 2018 were 0. 18% and 0.28%, respectively. Home discharge increased from 30.1% to 79.0% from 2001–2018. The values for these parameters are varied across the seven sites. Conclusion. The PAR can be used to develop best practices, analyze health-care economics, and promote evidence-based medicine. We are also developing a platform for registry development that can be exported by other hospitals that utilize an Epic-based record system. For any tables or figures, please contact the authors directly

Osteoarthritis (OA) is the fastest growing global health problem, with a total joint replacement being the only effective treatment for patients with end stage OA. Many groups are examining the use of bone marrow or adipose derived mesenchymal stem cells (MSCs) to repair cartilage, or modulate inflammation to promote healing, however, little efficacy in promoting cartilage repair, or reducing patient symptoms over temporary treatments such as micro-fracture has been observed. There is a growing body of literature demonstrating that MSCs derived from the synovial lining of the joint are superior in terms of chondrogenic differentiation and while improvements in clinical outcome measures have been observed with synovial MSCs, results from clinical studies are still highly variable. Based on our results, we believe this variability in clinical studies with MSCs results in part from the isolation, expansion and re-injection of distinct MSCs subtypes in normal vs. OA tissues, each with differing regenerating potential. However, it remains unknown if this heterogeneity is natural (e.g. multiple MSC subtypes present) or if MSCs are influenced by factors in vivo (disease state/stage). Therefore, in this study, we undertook an ‘omics’ screening approach on MSCs from normal and OA knee synovial tissue. Specifically, we characterized their global proteome and genomic expression patterns to determine if multiple MSC from normal and OA joints are distinct at the protein/gene expression level and/if so, what proteins/genes are differentially expressed between MSCs derived from normal and OA synovial tissue. Synovium tissue was collected from OA patients undergoing joint replacement and normal cadaveric knees. The in vitro adipogenic, chondrogenic and osteogenic differentiation potential of the MSCs was analyzed via qPCR and histology. Fully characterized MSC populations where then analyzed through an unbiased shotgun proteomics, and microarray analysis. Synovial MSCs isolated from both OA and normal knees demonstrated similar multipotent differentiation capacity. Likewise, both OA and normal MSCs display the typical MSCs cell surface marker profile in vitro (CD90+, CD44+, CD73+, CD105+). Using shotgun proteomics, 7720 unique peptides corresponding to 2183 proteins were identified and quantified between normal and OA MSCs. Of these 2183 proteins, 994 were equally expressed in normal and OA, MSCs, 324 were upregulated in OA MSCs (with 50 proteins exclusively expressed in OA MSCs), 630 proteins were upregulated in normal MSCs (with 16 proteins exclusively expressed in normal MSCs). Microarray analysis of normal and OA MSCs demonstrated a similar result in where, 967 genes were differentially expressed between normal and OA MSCs, with 423 genes upregulated in OA, and 544 genes upregulated in normal MSCs. In this project, we have demonstrated that although normal and OA synovial derived MSCs demonstrate similar multipotent differentiation potential and cell surface markers expression, these cells demonstrated significant differences at the molecular level (protein and gene expression). Further research is required to determine if these differences influence functional differences in vitro and/or in vivo and what drives this dramatic change in the regulatory pathways within normal vs. OA synovial MSCs

Introduction. Hypoalbuminemia has previously been identified as an independent predictor of postoperative complications following total knee arthroplasty (TKA). Given the morbidity and financial burden associated with TKA complications, significant effort has gone into identifying patients at increased risk for perioperative complications. The American Society of Anesthesiologists (ASA) physical status score has been utilized for risk stratification of surgical patients for many years and is a measure of overall health. However, it is unclear how measures like albumin compare to the prognostic ability of this type of global health measure. This study aims to elucidate the utility of preoperative albumin compared with that of the ASA score in predicting complications following TKA. Methods. Patients undergoing TKA between 2005 and 2015 were identified using the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database. Patients were stratified based on preoperative hypoalbuminemia (<3.5 g/dL) and ASA score (≤ 2 vs. > 2). Multivariable regression analysis adjusted for age, sex, BMI, and smoking status was utilized to determine predictive potential of hypoalbuminemia and ASA score on each postoperative complication. Results. Of the 79,661 patients included in the cohort, 4.3% had preoperative hypoalbuminemia. Univariate regression analysis found significant predictive abilities of both serum albumin and ASA score on numerous postoperative complications, such as superficial infection, deep infection, MI, pneumonia, renal insufficiency, reintubation, transfusion, readmission, reoperation, and death. Interestingly, multivariable regression analysis demonstrated that hypoalbuminemia more robustly predicted postoperative deep infection than ASA. Discussion and Conclusion. Hypoalbuminemia and ASA each individually predict numerous postoperative complications following TKA. However, this study suggests that while ASA score more accurately predicts post-operative medical complications, hypoalbuminemia may be a more accurate predictor of periprosthetic infection following TKA. Ultimately, preoperative albumin should be incorporated in the pre-operative work-up routine to stratify patient risk, especially regarding postoperative infection

Background & purpose. Measurement inconsistency across clinical trials is tackled by the development of a core outcome measurement set. Four core outcome domains were recommended for clinical trials in patients with non-specific LBP (nsLBP): physical functioning, pain intensity, health-related quality of life (HRQoL), and number of deaths. This study aimed to reach consensus on core instruments to measure the first three domains. Methods & Results. The Steering Committee overseeing this project selected 17 potential core instruments for physical functioning, three for pain intensity, and five for HRQoL. Evidence on their measurement properties in nsLBP was synthesized in three systematic reviews using COSMIN methodology. Researchers, clinicians, and patients (n = 208) were invited in a Delphi survey to seek consensus on which instruments to endorse as core. Consensus was a-priori set at 67% of participants agreeing on endorsing an instrument. Two Delphi rounds were run (response rates = 44% and 41%). Agreement was reached on endorsing the Oswestry Disability Index (ODI 2.1a) for physical functioning, the Numeric Rating Scale (NRS) for pain intensity, but not on other instruments. Several participants demanded to have free of charge core instruments. Taking these results into account, the steering committee formulated the following recommendations: ODI 2.1a or 24-item Roland Morris Disability Questionnaire for physical functioning, NRS for pain intensity, Short-Form 12 or 10-item PROMIS Global Health for HRQoL. Conclusion. A core outcome measurement set is available for clinical trials in patients with nsLBP. High quality clinimetric studies directly comparing recommended and not recommended instruments are required. Conflict of interest: None. Source of funding: EUROSPINE, The Spine Society of Europe

There has been a recent surge in the creation of medical student-led and foundation trainees-led research collaboratives in surgery. These have mainly been in general surgery. The current study therefore explores the value and feasibility of such collaboratives, highlighting the scope for a similar idea in orthopaedics. Research Collaborative organisations were systematically searched and reviewed to check whether medical students or junior doctors prior to speciality training led them. The advertised research projects and subsequent publication productivity for each identified organisation was also evaluated using the information presented on their websites. Two medical student-led research collaborative organisations and 1 medical student and foundation trainees-led research collaborative were identified. All of which are in general surgery and none in trauma and/or orthopaedics surgery. These include STARSurg, EuroSurg and GlobalSurg respectively. A total of 6 research collaborative projects were identified with 3 leading to subsequent publications. This study highlights the value and feasibility of medical students- and foundation trainees-driven high quality surgical research collaborative. It also emphasises the growing contribution of medical students towards research and policymaking in our global health system, an aspect that may be absent or delayed in the field of orthopaedics. We therefore, explore the idea as well as the need to instigate a similar collaboration in the field of trauma and orthopaedic surgery

We set out to determine the impact of surgery on quality of life and function in patients who had undergone surgery for symptomatic peri-acetabular metastases. From a prospective database we retrospectively reviewed 46 consecutive patients who had been treated operatively between June 2003 and June 2009. The mean age of the patients was 56.4 years (20 to 73) and the mean post-operative follow-up was 19.2 months (4 to 70). Functional evaluation and quality-of-life assessments were performed. At the most recent follow-up, 26 patients (56.5%) were alive. Their median survival time was 25.0 months. Ten major postoperative complications had occurred in eight patients (17.4%). The mean post-operative Musculoskeletal Tumor Society score (MSTS 93) was 56.3% (6.7% to 90.0%). Improvement in the Eastern Cooperative Oncology Group (ECOG) performance status was seen in 32 patients (69.6%). On the European Organisation for Research and Treatment of Cancer core quality-of-life questionnaire (QLQ-C30) measure of global health status there was a statistically significant improvement from the patients’ pre-operative status (42.8 (. sd. 13.7)) to that found at the latest follow-up (58.0 (. sd. 12.5)) (p = 0.001). The only statistically significant change in the nine symptom domains of the QLQ-C30 was a reduction in the mean level of pain (from 59.1 to 29.5 (out of 100)) (p < 0.001). Surgery for patients with peri-acetabular metastases reduces pain and improves their quality of life, and has a low rate of surgical complications

Osteoporosis is a global health issue with 200 million people suffering worldwide and it is a common condition in the elderly. Bisphosphonates including alendronate and risendronate are considered as the first line treatment for osteoporosis. However, there is increasing evidence that bisphosphonate (BP) therapy is associated with atypical fractures. Animal studies have reported a dose-dependent association between the duration of BP therapy and the accumulation of micro-damage. We tested the hypothesis that hip fracture patients treated with BP exhibited greater micro-damage density than untreated fracture and ‘healthy’ aging non-fracture controls. Trabecular bone cores from patients treated with BP were compared with patients who had not received any treatment for bone metabolic disease (ethics reference: R13004). Non-fractured cadaveric femora from individuals with no history of bone metabolic disease were used as controls. Cores were imaged in high spatial resolution (∼1.3µm) using Synchrotron X-ray tomography (Diamond Light Source Ltd.) A novel classification system was devised to characterise features of micro-damage in the Synchrotron images: micro-cracks, diffuse damage and perforations. Synchrotron micro-CT stacks were visualised and analysed using ImageJ, Avizo and VGStudio MAX. Our findings show that the BP group had the highest micro-damage density across all groups. The BP group (7.7/mm. 3. ) also exhibited greater micro-crack density than the fracture (4.3/mm. 3. ) and non-fracture (4.1/mm. 3. ) controls. Furthermore, the BP group (1.9/mm. 3. ) demonstrated increased diffuse damage when compared to the fracture (0.3/mm. 3. ) and non-fracture (0.8/mm. 3. ) controls. In contrast, the BP group (1.9mm. 3. ) had fewer perforations than fracture (3.0/mm. 3. ) and non-fracture controls (3.9/mm. 3. ). BP inhibits bone remodelling, thereby reducing the number of perforated trabeculae, but over-suppression leads to micro-damage accumulation. Accumulated damage could weaken the trabecular bone in the femoral head and neck, increasing the risk of a fracture during a trip or fall

The World Health Organisation (WHO) has recently identified musculoskeletal care as a major global health issue in the developing world. However, little is known about the quality and trends of orthopaedic research in resource-poor settings. The purpose of this study was to perform a systematic review of orthopaedic research in low-income countries (LIC). The primary objective was to determine the quality and publication parameters of studies performed in LIC. Secondary objectives sought to provide recommendations for successful strategies to implement research endeavors in LIC. A systematic review of the literature was performed by searching MEDLINE (1966-November 2014), EMBASE and the Cochrane Library to identify peer-reviewed orthopaedic research conducted in LICs. The PRISMA guidelines for performing a systematic review were followed. LIC were defined by the WHO and by the World Bank as countries with gross national income per capita equal or less than 1045US$. Inclusion criteria were (1) studies performed in a LIC, (2) conducted on patients afflicted by an orthopaedic condition, and (3) evaluated either an orthopaedic intervention or outcome. The Oxford Centre for Evidence-Based Medicine Levels of Evidence, and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to objectively rate the overall methodological quality of each study. Additional data collected from these studies included the publication year, journal demographics, orthopaedic subspecialty and authors' country of origin. A total of 1,809 articles were screened and 277 studies met our inclusion criteria. Eighty-eight percent of studies conducted in LIC were of lower quality evidence according to the GRADE score and consisted mostly of small case series or case reports. Bangladesh and Nepal were the only two LIC with national journals and produced the highest level of research evidence. Foreign researchers produced over 70% of the studies with no collaboration with local LIC researchers. The most common subspecialties were trauma (42%) and paediatrics (14%). The 3 most frequent countries where the research originated were the United States (42%), United Kingdom (11%), and Canada (8%). The 3 most common locations where research was conducted were Haiti (18%), Afghanistan (14%), and Malawi (7%). The majority of orthopaedic studies conducted in LIC were of lower quality and performed by foreign researchers with little local collaboration. In order to promote the development of global orthopaedic surgery and research in LIC, we recommend (1) improving the collaboration between researchers in developed and LIC, (2) promoting the teaching of higher-quality and more rigorous research methodology through shared partnerships, (3) improving the capacity of orthopaedic research in developing nations through national peer-reviewed journals, and (4) dedicated subsections in international orthopaedic journals to global healthcare research

Aims

The optimal bearing surface design for medial unicompartmental knee arthroplasty (UKA) remains controversial. The aim of this study was to compare outcomes of fixed-bearing (FB) and mobile-bearing (MB) UKAs from a single high-volume institution.

Aims

The Vantage Total Ankle System is a fourth-generation low-profile fixed-bearing implant that has been available since 2016. We aimed to describe our early experience with this implant.

Musculoskeletal diseases are having a growing impact worldwide. It is therefore crucial to have an evidence base to most effectively and efficiently implement future health services across different healthcare systems. International trials are an opportunity to address these challenges and have many potential benefits. They are, however, complex to set up and deliver, which may impact on the efficient and timely delivery of a project. There are a number of models of how international trials are currently being delivered across a range of orthopaedic patient populations, which are discussed here. The examples given highlight that the key to overcoming these challenges is the development of trusted and equal partnerships with collaborators in each country. International trials have the potential to address a global burden of disease, and in turn optimize the benefit to patients in the collaborating countries and those with similar health services and care systems.

Cite this article: Bone Joint J 2023;105-B(7):719–722.

Quadriceps femoris muscle weakness has long been associated with disuse atrophy in symptomatic knee osteoarthritis but more recently implicated in the aetiology of this condition. The purpose of this study was to assess the benefits of two interventions aimed at increasing quadriceps strength in subjects with moderate to severe knee osteoarthritis. Twenty-eight patients, aged fifty-five to seventy-five, were recruited and randomised to either a six-week home resistance-training exercise program or a six-week neuromuscular electrical stimulation (NMES) program. Eleven patients matched for age, gender and osteoarthritis severity formed a control group, receiving standard care. The resistance-training group performed six exercises three times per week, while the NMES group used the garment stimulator for twenty minutes five times per week Outcome measures included isometric and isokinetic quadriceps strength, functional capacity, quadriceps cross-sectional area, and validated health survey scores. These measures were assessed at baseline, post-intervention and at 6-weeks post-intervention. Both intervention groups showed significant improvements in all functional tests, in the global health survey, and in quadriceps cross-sectional area immediately post-intervention. An increase in isokinetic strength was seen in the exercise group only. With the exception of isokinetic strength, all benefits were maintained six weeks post-intervention. Both a six-week home resistance-training program and a six-week NMES program produce significant improvements in functional performance as well as physical and mental health for patients with moderate to severe knee osteoarthritis. Home-based NMES is an acceptable alternative to physical therapy, and is especially appropriate for patients who have difficulty complying with an exercise program

The December 2022 Shoulder & Elbow Roundup³⁶⁰ looks at: Biceps tenotomy versus soft-tissue tenodesis in females aged 60 years and older with rotator cuff tears; Resistance training combined with corticosteroid injections or tendon needling in patients with lateral elbow tendinopathy; Two-year functional outcomes of completely displaced midshaft clavicle fractures in adolescents; Patients who undergo rotator cuff repair can safely return to driving at two weeks postoperatively; Are two plates better than one? A systematic review of dual plating for acute midshaft clavicle fractures; Treatment of acute distal biceps tendon ruptures; Rotator cuff tendinopathy: disability associated with depression rather than pathology severity; Coonrad-Morrey total elbow arthroplasty implications in young patients with post-traumatic sequelae.

Aims

The primary aim of this prospective, multicentre study is to describe the rates of returning to golf following hip, knee, ankle, and shoulder arthroplasty in an active golfing population. Secondary aims will include determining the timing of return to golf, changes in ability, handicap, and mobility, and assessing joint-specific and health-related outcomes following surgery.