Identifying collagen VI as a target of fibrotic diseases regulated by CREBBP/EP300.

Fibrotic diseases remain a major cause of morbidity and mortality, yet there are few effective therapies. The underlying pathology of all fibrotic conditions is the activity of myofibroblasts. Using cells from freshly excised disease tissue from patients with Dupuytren's disease (DD), a localized fibrotic disorder of the palm, we sought to identify new therapeutic targets for fibrotic disease. We hypothesized that the persistent activity of myofibroblasts in fibrotic diseases might involve epigenetic modifications. Using a validated genetics-led target prioritization algorithm (Pi) of genome wide association studies (GWAS) data and a broad screen of epigenetic inhibitors, we found that the acetyltransferase CREBBP/EP300 is a major regulator of contractility and extracellular matrix production via control of H3K27 acetylation at the profibrotic genes, ACTA2 and COL1A1 Genomic analysis revealed that EP300 is highly enriched at enhancers associated with genes involved in multiple profibrotic pathways, and broad transcriptomic and proteomic profiling of CREBBP/EP300 inhibition by the chemical probe SGC-CBP30 identified collagen VI (Col VI) as a prominent downstream regulator of myofibroblast activity. Targeted Col VI knockdown results in significant decrease in profibrotic functions, including myofibroblast contractile force, extracellular matrix (ECM) production, chemotaxis, and wound healing. Further evidence for Col VI as a major determinant of fibrosis is its abundant expression within Dupuytren's nodules and also in the fibrotic foci of idiopathic pulmonary fibrosis (IPF). Thus, Col VI may represent a tractable therapeutic target across a range of fibrotic disorders.

Surgery versus cast immobilisation for adults with a bicortical fracture of the scaphoid waist (SWIFFT): a pragmatic, multicentre, open-label, randomised superiority trial.

BACKGROUND: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. The use of immediate surgical fixation to manage this type of fracture has increased, despite insufficient evidence of improved outcomes over non-surgical management. The SWIFFT trial compared the clinical effectiveness of surgical fixation with cast immobilisation and early fixation of fractures that fail to unite in adults with scaphoid waist fractures displaced by 2 mm or less. METHODS: This pragmatic, parallel-group, multicentre, open-label, two-arm, randomised superiority trial included adults (aged 16 years or older) who presented to orthopaedic departments of 31 hospitals in England and Wales with a clear bicortical fracture of the scaphoid waist on radiographs. An independent remote randomisation service used a computer-generated allocation sequence with randomly varying block sizes to randomly assign participants (1:1) to receive either early surgical fixation (surgery group) or below-elbow cast immobilisation followed by immediate fixation if non-union of the fracture was confirmed (cast immobilisation group). Randomisation was stratified by whether or not there was displacement of either a step or a gap of 1-2 mm inclusive on any radiographic view. The primary outcome was the total patient-rated wrist evaluation (PRWE) score at 52 weeks after randomisation, and it was analysed on an available case intention-to-treat basis. This trial is registered with the ISRCTN registry, ISRCTN67901257, and is no longer recruiting, but long-term follow-up is ongoing. FINDINGS: Between July 23, 2013, and July 26, 2016, 439 (42%) of 1047 assessed patients (mean age 33 years; 363 [83%] men) were randomly assigned to the surgery group (n=219) or to the cast immobilisation group (n=220). Of these, 408 (93%) participants were included in the primary analysis (203 participants in the surgery group and 205 participants in the cast immobilisation group). 16 participants in the surgery group and 15 participants in the cast immobilisation group were excluded because of either withdrawal, no response, or no follow-up data at 6, 12, 26, or 52 weeks. There was no significant difference in mean PRWE scores at 52 weeks between the surgery group (adjusted mean 11·9 [95% CI 9·2-14·5]) and the cast immobilisation group (14·0 [11·3 to 16·6]; adjusted mean difference -2·1 [95% CI -5·8 to 1·6], p=0·27). More participants in the surgery group (31 [14%] of 219 participants) had a potentially serious complication from surgery than in the cast immobilisation group (three [1%] of 220 participants), but fewer participants in the surgery group (five [2%]) had cast-related complications than in the cast immobilisation group (40 [18%]). The number of participants who had a medical complication was similar between the two groups (four [2%] in the surgery group and five [2%] in the cast immobilisation group). INTERPRETATION: Adult patients with scaphoid waist fractures displaced by 2 mm or less should have initial cast immobilisation, and any suspected non-unions should be confirmed and immediately fixed with surgery. This treatment strategy will help to avoid the risks of surgery and mostly limit the use of surgery to fixing fractures that fail to unite. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Content validity and responsiveness of the Patient-Specific Functional Scale in patients with Dupuytren's disease.

INTRODUCTION: Patient-reported outcome measures have become the standard tool for reflecting the patient's perspective on their treatment outcome for a wide variety of hand conditions. The Patient-Specific Functional Scale (PSFS), is an individualized questionnaire that enables patients to specify those activities with which they have difficulty in daily life. PURPOSE OF THE STUDY: This study aims to determine the content validity and responsiveness of the PSFS compared with the Michigan Hand Questionnaire (MHQ) in patients with Dupuytren's disease. STUDY DESIGN: Multicentre inception cohort. METHODS: Patients with Dupuytren's disease being treated with percutaneous needle aponeurotomy, limited fasciectomy, or skin graft were selected from a database with routine outcome measurements in usual care. To assess content validity of the PSFS, the activities specified by patients were classified into the International Classification of Function core set for hand conditions. The standardized response mean is calculated for the pre- and post-change scores of the PSFS to evaluate responsiveness. RESULTS: Three hundred and eight patients were analyzed before and three months after treatment. Content validity of the PSFS was appropriate because 95% of all items could be classified into the International Classification of Function activities and participation domain. The standardized response mean of the PSFS was 1.0 (95% confidence interval, 0.86-1.2), which was substantially larger than the standardized response mean of the MHQ score 0.58 (95% confidence interval, 0.42-0.74). DISCUSSION: The PSFS is a content-valid questionnaire which may be more responsive to change than a fixed-item instrument such as the MHQ in patients with Dupuytren's disease. CONCLUSIONS: The PSFS is a valuable tool to set therapy goals and evaluate the progress over time in patients with Dupuytren's disease.

Return to work after carpal tunnel release surgery: a qualitative interview study.

BACKGROUND: Carpal tunnel syndrome is a common nerve compression disorder which affects hand sensation and function. Carpal tunnel release surgery (CTR) is frequently performed to alleviate these symptoms. For many CTR patients, surgery occurs during their working lifetime, but there is currently no evidence-based guidance to inform clinicians or patients when it might be safe to return to different types of work afterwards. The aim of this qualitative study was to explore the return to work experiences of patients who had recently undergone CTR. METHODS: Semi-structured 1:1 interviews were conducted with a subgroup of participants recruited to a multi-centre prospective cohort study. Interviewees were purposely selected to represent a range of demographic, clinical and occupational characteristics. All had recently undergone CTR and had returned to work. Interviews were audio recorded, transcribed verbatim and analysed using the framework method. Participants were recruited until data saturation was achieved. RESULTS: Fourteen participants were interviewed: 11 women (median age 49 years, range 27-61) and 3 men (age range 51-68 years). Three key themes were identified. Theme 1 centred on the level of functional disability experienced immediately after surgery. There was an expectation that CTR would be a 'minor' procedure, but this did not match the participants' experiences. Theme 2 explored the desire for validation for the time away from work, with participants recalling a need to justify their work absence to themselves as well as to their employers. Theme 3 focused on the participants' reflections of handing their return to work and function, with many reporting uncertainties about what constituted appropriate activity loads and durations. There was a desire for specific information relating to individual work roles. CONCLUSION: Individual return to work decision-making was largely influenced by the recommendations received. According to the views of participants, clinicians may be able to prepare patients better pre-operatively, especially with respect to function in the immediate post-operative period and by providing return to work guidance that can be tailored for individual work roles.

Patient Satisfaction With Collagenase.

PURPOSE: To establish patient satisfaction after collagenase clostridium histolyticum (CCH) injection. METHODS: In a cross-sectional study, 213 patients who had been treated for Dupuytren disease with CCH were reviewed between 37 and 1421 days after injection. RESULTS: A total of 73% of the patients were very satisfied or satisfied, and 21% were dissatisfied; 75% would probably or definitely have CCH again, whereas 17% probably or definitely would not. We found that satisfaction and willingness to undergo a second treatment decreased over time and had a negative relationship with recurrence. Dissatisfaction was greater in those with a poor initial outcome but not in those with an initial complication. Of 212 patients, 78 had previously experienced surgery for Dupuytren disease of whom 71% would prefer CCH to surgery and 15% the converse. Satisfaction shows a relationship with function as measured by both QuickDASH and the Southampton Dupuytren Scoring Scheme. CONCLUSIONS: Patient satisfaction with CCH is generally high but deteriorates over time as the disease recurs. To manage patient expectation, this issue should be made explicit to patients in the consent process. CLINICAL RELEVANCE: Overall satisfaction with CCH is high, with initial satisfaction rates especially good. Forewarning of complications and recurrence can help maintain satisfaction levels.

Investigation of the short-term in vivo performance of metal-on-carbon fibre reinforced poly ether ether ketone Motec wrists: an explant analysis.

Total wrist arthroplasty (TWA) aims to restore pain-free motion to diseased joints. One such TWA, the Motec, has demonstrated good results with acceptable complication rates. It has recently been suggested that the metal-on-carbon fibre reinforced poly ether ether ketone (Mo-CFR-PEEK) version of the Motec TWA be implanted instead of the metal-on-metal version. An explant analysis was undertaken on seven Motec Mo-CFR-PEEK TWAs, revised for a variety of reasons, after a mean time of 2 years in vivo. Compared to a new Motec implant, five of the explanted metal heads and three of the CFR-PEEK cups became smoother in vivo, suggesting self-polishing and negative skewness, indicating some material loss in vivo. Two explanted cups showed indentation marks on their rims and one of these was from component impingement with embedded metallic debris. In the short-term, the articulating surfaces of Motec Mo-CFR-PEEK TWAs did not show major damage.Level of evidence: IV.

Radiological outcomes following surgical fixation with wires versus moulded cast for patients with a dorsally displaced fracture of the distal radius: a radiographic analysis from the DRAFFT2 trial.

Aims: The primary aim of this study was to report the radiological outcomes of patients with a dorsally displaced distal radius fracture who were randomized to a moulded cast or surgical fixation with wires following manipulation and closed reduction of their fracture. The secondary aim was to correlate radiological outcomes with patient-reported outcome measures (PROMs) in the year following injury. Methods: Participants were recruited as part of DRAFFT2, a UK multicentre clinical trial. Participants were aged 16 years or over with a dorsally displaced distal radius fracture, and were eligible for the trial if they needed a manipulation of their fracture, as recommended by their treating surgeon. Participants were randomly allocated on a 1:1 ratio to moulded cast or Kirschner wires after manipulation of the fracture in the operating theatre. Standard posteroanterior and lateral radiographs were performed in the radiology department of participating centres at the time of the patient's initial assessment in the emergency department and six weeks postoperatively. Intraoperative fluoroscopic images taken at the time of fracture reduction were also assessed. Results: Patients treated with surgical fixation with wires had less dorsal angulation of the radius versus those treated in a moulded cast at six weeks after manipulation of the fracture; the mean difference of -4.13° was statistically significant (95% confidence interval 5.82 to -2.45). There was no evidence of a difference in radial shortening. However, there was no correlation between these radiological measurements and PROMs at any timepoint in the 12 months post-injury. Conclusion: For patients with a dorsally displaced distal radius fracture treated with a closed manipulation, surgical fixation with wires leads to less dorsal angulation on radiographs at six weeks compared with patients treated in a moulded plaster cast alone. However, the difference in dorsal angulation was small and did not correlate with patient-reported pain and function.

Can learnings from the COVID-19 pandemic improve trial conduct post-pandemic? A case study of strategies used by the DISC trial.

Background: RCTs often face issues such as slow recruitment, poor intervention adherence and high attrition, however the 2020/2021 COVID-19 pandemic intensified these challenges. Strategies employed by the DISC trial to overcome pandemic-related barriers to recruitment, treatment delivery and retention may be useful to help overcome routine problems. Methods: A structured survey and teleconference with sites was undertaken. Key performance indicators in relation to recruitment, treatment delivery and retention were compared descriptively before and after the pandemic started. This was situated also in relation to qualitative opinions of research staff. Results: Prior to the pandemic, retention was 93.6%. Increased support from the central trial management team and remote data collection methods kept retention rates high at 81.2% in the first 6 months of the pandemic, rising to 89.8% in the subsequent 6 months. Advertising the study to patients resulted in 12.8 patients/month enquiring about participation, however only six were referred to recruiting sites. Sites reported increased support from junior doctors resolved research nurse capacity issues. One site avoided long delays by using theatre space in a private hospital. Conclusions: Recruitment post-pandemic could be improved by identification of barriers, increased support from junior doctors through the NIHR associate PI scheme and advertising. Remote back-up options for data collection can keep retention high while reducing patient and site burden. To future proof studies against similar disruptions and provide more flexibility for participants, we recommend that RCTs have a back-up option of remote recruitment, a back-up location for surgeries and flexible approaches to collecting data.

Examining the benefit of graduated compression stockings in the prevention of hospital-associated venous thromboembolism in low-risk surgical patients: a multicentre cluster randomised controlled trial (PETS trial).

INTRODUCTION: Hospital-acquired thrombosis (HAT) is defined as any venous thromboembolism (VTE)-related event during a hospital admission or occurring up to 90 days post discharge, and is associated with significant morbidity, mortality and healthcare-associated costs. Although surgery is an established risk factor for VTE, operations with a short hospital stay (<48 hours) and that permit early ambulation are associated with a low risk of VTE. Many patients undergoing short-stay surgical procedures and who are at low risk of VTE are treated with graduated compression stockings (GCS). However, evidence for the use of GCS in VTE prevention for this cohort is poor. METHODS AND ANALYSIS: A multicentre, cluster randomised controlled trial which aims to determine whether GCS are superior in comparison to no GCS in the prevention of VTE for surgical patients undergoing short-stay procedures assessed to be at low risk of VTE. A total of 50 sites (21 472 participants) will be randomised to either intervention (GCS) or control (no GCS). Adult participants (18-59 years) who undergo short-stay surgical procedures and are assessed as low risk of VTE will be included in the study. Participants will provide consent to be contacted for follow-up at 7-days and 90-days postsurgical procedure. The primary outcome is the rate of symptomatic VTE, that is, deep vein thrombosis or pulmonary embolism during admission or within 90 days. Secondary outcomes include healthcare costs and changes in quality of life. The main analysis will be according to the intention-to-treat principle and will compare the rates of VTE at 90 days, measured at an individual level, using hierarchical (multilevel) logistic regression. ETHICS AND DISSEMINATION: Ethical approval was granted by the Camden and Kings Cross Research Ethics Committee (22/LO/0390). Findings will be published in a peer-reviewed journal and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN13908683.

Diagnosis and Treatment of Carpometacarpal Instability.

Hypermobility of the first CMC joint may adversely affect hand function and may lead to osteoarthritis later in life. It presents more commonly in younger women with generalized joint hypermobility or postmenopausal women with early stages of arthritis. It may follow trauma and deletive surgical interventions. Clinically, joint subluxation manifests with a prominent and unstable thumb base, and is radiographically confirmed by stress views. A variety of ligament reconstruction techniques are available to stabilize the CMC joint including open ligament reconstruction with or without temporary Kirschner-wire fixation, arthroscopic debridement with capsular shrinkage, metacarpal extension osteotomy, internal proprietary anchors, and arthrodesis.

Dupuytren's disease: using needles more across the world.

In this article we take an international perspective on the use of needles, either percutaneous needle fasciotomy (PNF) or Clostridial Collagenase Histiolyticum (CCH), in treating Dupuytren's Disease (DD). Worldwide, PNF is now used more frequently. The CCH has been withdrawn from non-USA markets, which lessens its use. Different patients have different preferences, while different surgeons have different skills and opinions. The surgeon should fully consider the patient's preference and should also, in view of the scarcity of surgical resource and the potential hazard of surgery, reconsider and expand the use of a needle rather than an operation. In the future, a cheaper, yet equally safe and effective alternative to CCH, will provide a useful clinical tool for those cords, which, in the surgeon's personal Venn diagram, are too challenging for PNF, but the patient does not want to have surgery.

Sickness absence after carpal tunnel release: a multicentre prospective cohort study.

OBJECTIVES: To describe when patients return to different types of work after elective carpal tunnel release (CTR) surgery and identify the factors associated with the duration of sickness absence. DESIGN: Multicentre prospective observational cohort study. SETTING AND PARTICIPANTS: Participants were recruited preoperatively from 16 UK centres and clinical, occupational and demographic information were collected. Participants completed a weekly diary and questionnaires at four and 12 weeks postoperatively. OUTCOMES: The main outcome was duration of work absence from date of surgery to date of first return to work. RESULTS: 254 participants were enrolled in the study and 201 provided the follow-up data. Median duration of sickness absence was 20 days (range 1-99). Earlier return to work was associated with having surgery in primary care and a self-reported work role involving more than 4 hours of daily computer use. Being female and entitlement to more than a month of paid sick leave were both associated with longer work absences. The duration of work absence was strongly associated with the expected duration of leave, as reported by participants before surgery. Earlier return to work was not associated with poorer clinical outcomes reported 12 weeks after CTR. CONCLUSIONS: There was wide variation in the duration of work absence after CTR across all occupational categories. A combination of occupational, demographic and clinical factors was associated with the duration of work absence, illustrating the complexity of return to work decision making. However, preoperative expectations were strongly associated with the actual duration of leave. We found no evidence that earlier return to work was harmful. Clear, consistent advice from clinicians preoperatively setting expectations of a prompt return to work could reduce unnecessary sickness absence after CTR. To enable this, clinicians need evidence-informed guidance about appropriate timescales for the safe return to different types of work.

Dupuytren's interventions surgery versus collagenase (DISC) trial: study protocol for a pragmatic, two-arm parallel-group, non-inferiority randomised controlled trial.

BACKGROUND: Dupuytren's contracture is a fibro-proliferative disease of the hands affecting over 2 million UK adults, particularly the white, male population. Surgery is the traditional treatment; however, recent studies have indicated that an alternative to surgery-collagenase clostridium histolyticum (collagenase)-is better than a placebo in the treatment of Dupuytren's contracture. There is however no robust randomised controlled trial that provides a definitive answer on the clinical effectiveness of collagenase compared with limited fasciectomy surgery. Dupuytren's intervention surgery vs collagenase trial (DISC) trial was therefore designed to fill this evidence gap. METHODS/DESIGN: The DISC trial is a multi-centre pragmatic two-arm parallel-group, randomised controlled trial. Participants will be assigned 1:1 to receive either collagenase injection or surgery (limited fasciectomy). We aim to recruit 710 adult participants with Dupuytren's contracture. Potential participants will be identified in primary and secondary care, screened by a delegated clinician and if eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported patient evaluation measure assessed 1 year after treatment. Secondary outcome measures include the Unité Rhumatologique des Affections de la Main Scale, the Michigan Hand Questionnaire, EQ-5D-5L, resource use, further procedures, complications, recurrence, total active movement and extension deficit, and time to return to function. Given the limited evidence comparing recurrence rates following collagenase injection and limited fasciectomy, and the importance of a return to function as soon as possible for patients, the associated measures for each will be prioritised to allow treatment effectiveness in the context of these key elements to be assessed. An economic evaluation will assess the cost-effectiveness of treatments, and a qualitative sub-study will assess participants' experiences and preferences of the treatments. DISCUSSION: The DISC trial is the first randomised controlled trial, to our knowledge, to investigate the clinical and cost-effectiveness of collagenase compared to limited fasciectomy surgery for patients with Dupuytren's contracture. TRIAL REGISTRATION: Clinical.Trials.gov ISRCTN18254597 . Registered on April 11, 2017.

How a Nationalized Health Care System Influences Hand Surgery Practice: The United Kingdom Perspective.

The United Kingdom's health care is provided free at the point of delivery by the National Health Service (NHS). The NHS uses an internal market model to fund health care, as opposed to using a provider-purchaser partnership model. Hand surgery is provided by plastic surgeons and trauma and orthopaedic surgeons. The nationalized system has disadvantages and benefits. This environment is heavily cost controlled, with some restrictions on individual practice and associated long waiting times. The advantages include a large population base for research in hand surgery and careful monitoring systems for problems with devices and recommendations for various treatments.

Compression stockings in addition to low-molecular-weight heparin to prevent venous thromboembolism in surgical inpatients requiring pharmacoprophylaxis: the GAPS non-inferiority RCT.

BACKGROUND: Patients admitted to hospital for surgery are at an increased risk of venous thromboembolism. Pharmaco-thromboprophylaxis and mechanical prophylaxis (usually graduated compression stockings or intermittent pneumatic compression) have been shown to reduce the incidence of venous thromboembolism. The evidence base supporting the National Institute for Health and Care Excellence's recommendation for the use of graduated compression stockings for venous thromboembolism prevention in the UK has recently been challenged. It is unclear if the risks and costs associated with graduated compression stockings are justified for deep-vein thrombosis prevention in moderate- and high-risk elective surgical inpatients receiving low-dose low-molecular-weight heparin pharmaco-thromboprophylaxis. OBJECTIVES: The primary objective was to compare the venous thromboembolism rate in elective surgical inpatients at moderate or high risk of venous thromboembolism who were receiving either graduated compression stockings and low-dose low-molecular-weight heparin (standard care) or low-dose low-molecular-weight heparin alone (intervention). DESIGN: This was a pragmatic, multicentre, prospective, non-inferiority, randomised controlled trial. SETTING: This took place in secondary care NHS hospitals in the UK. PARTICIPANTS: Patients aged ≥ 18 years who were assessed to be at moderate or high risk of venous thromboembolism according to the NHS England venous thromboembolism risk assessment tool (or the trust equivalent based on this form) and who were not contraindicated to low-molecular-weight heparin or graduated compression stockings were deemed eligible to take part. INTERVENTIONS: Participants were randomised 1 : 1 to either low-molecular-weight heparin or low-molecular-weight heparin and graduated compression stockings. MAIN OUTCOME MEASURES: The primary outcome measure was venous thromboembolism up to 90 days after surgery. A combined end point of duplex ultrasound-proven new lower-limb deep-vein thrombosis (symptomatic or asymptomatic) plus imaging-confirmed symptomatic pulmonary embolism. Secondary outcomes included quality of life, compliance with graduated compression stockings and low-molecular-weight heparin during admission, and all-cause mortality. RESULTS: A total of 1905 participants were randomised and 1858 were included in the intention-to-treat analysis. A primary outcome event occurred in 16 out of 937 (1.7%) patients in the low-molecular-weight heparin-alone arm compared with 13 out of 921 (1.4%) patients in the low-molecular-weight heparin plus graduated compression stockings arm. The risk difference between low-molecular-weight heparin and low-molecular-weight heparin plus graduated compression stockings was 0.30% (95% confidence interval -0.65% to 1.26%). As the 95% confidence interval did not cross the non-inferiority margin of 3.5% (p < 0.001 for non-inferiority), the results indicate that non-inferiority of low-molecular-weight heparin alone was shown. LIMITATIONS: In total, 13% of patients did not receive a duplex ultrasound scan that could have detected further asymptomatic deep-vein thrombosis. However, missing scans were balanced between both trial arms. The subpopulation of those aged ≥ 65 years assessed as being at a moderate risk of venous thromboembolism was under-represented in the study; however, this reflects that this group is under-represented in the general population. CONCLUSIONS: For elective surgical patients at moderate or high risk of venous thromboembolism, administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and graduated compression stockings. These findings indicate that graduated compression stockings may be unnecessary for most elective surgical patients. FUTURE WORK: Further studies are required to evaluate whether or not adjuvant graduated compression stockings have a role in patients receiving extended thromboprophylaxis, beyond the period of hospital admission, following elective surgery or in patients undergoing emergency surgical procedures. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13911492. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 69. See the NIHR Journals Library website for further project information.

WHY DID WE CONDUCT THIS RESEARCH?: People undergoing operations are at risk of developing blood clots in their legs, which is known as a deep-vein thrombosis. Blood clots occur for several reasons, such as not being able to move around after an operation, changes in the blood or damage to the veins in which blood travels. To decrease the risk of getting deep-vein thrombosis, patients having operations are given tight elastic socks to wear called graduated compression stockings. They are also given blood thinning medicine to prevent clotting. There is little evidence that wearing elastic socks in hospital will reduce the risk of blood clots if blood thinners are also given. Many patients say that the socks can hurt or cause bruising and can be difficult to put on. The graduated compression as an adjunct to thromboprophylaxis in surgery (GAPS) trial investigated whether or not patients having an operation would benefit from wearing elastic socks as well as getting blood thinners, or if blood thinners on their own prevented blood clots. WHAT DID WE DO?: A total of 1905 patients who were having operations at seven hospitals in England agreed to take part. They were randomly assigned to different treatments by a computer program. Half of the patients were given elastic socks plus blood thinners, and the other half were given the blood thinners alone. WHAT DID WE FIND?: There was no significant difference in the number of people who had a blood clot in either study group. This could mean that blood thinners are as good at stopping blood clots as blood thinners and elastic socks for patients having operations. WHAT COULD BE CARRIED OUT NEXT?: The NHS spends around £63M per year across England on elastic stockings. This research indicates that patients might not get extra benefit from wearing them if they have taken blood thinners.

Graduated compression stockings as adjuvant to pharmaco-thromboprophylaxis in elective surgical patients (GAPS study): randomised controlled trial.

OBJECTIVES: To investigate whether the use of graduated compression stockings (GCS) offers any adjuvant benefit when pharmaco-thromboprophylaxis is used for venous thromboembolism prophylaxis in patients undergoing elective surgery. DESIGN: Open, multicentre, randomised, controlled, non-inferiority trial. SETTING: Seven National Health Service tertiary hospitals in the United Kingdom. PARTICIPANTS: 1905 elective surgical inpatients (≥18 years) assessed as being at moderate or high risk of venous thromboembolism were eligible and consented to participate. INTERVENTION: Participants were randomly assigned (1:1) to receive low molecular weight heparin (LMWH) pharmaco-thromboprophylaxis alone or LMWH pharmaco-thromboprophylaxis and GCS. OUTCOME MEASURES: The primary outcome was imaging confirmed lower limb deep vein thrombosis with or without symptoms, or pulmonary embolism with symptoms within 90 days of surgery. Secondary outcome measures were quality of life, compliance with stockings and LMWH, lower limb complications related to GCS, bleeding complications, adverse reactions to LMWH, and all cause mortality. RESULTS: Between May 2016 and January 2019, 1905 participants were randomised. 1858 were included in the intention to treat analysis (17 were identified as ineligible after randomisation and 30 did not undergo surgery). A primary outcome event occurred in 16 of 937 (1.7%) patients in the LMWH alone group compared with 13 of 921 (1.4%) in the LMWH and GCS group. The risk difference between the two groups was 0.30% (95% confidence interval -0.65% to 1.26%). Because the 95% confidence interval did not cross the non-inferiority margin of 3.5% (P<0.001 for non-inferiority), LMWH alone was confirmed to be non-inferior. CONCLUSIONS: For patients who have elective surgery and are at moderate or high risk of venous thromboembolism, administration of pharmaco-thromboprophylaxis alone is non-inferior to a combination of pharmaco-thromboprophylaxis and GCS. These findings indicate that GCS might be unnecessary in most patients undergoing elective surgery. TRIAL REGISTRATION: ISRCTN13911492.

Mercury vapor volatilization from particulate generated from dental amalgam removal with a high-speed dental drill - a significant source of exposure.

BACKGROUND: The ubiquitous use of dental amalgam for over 180 years has resulted in the exposure of millions of dental workers to mercury. Dental amalgam contains approximately 50% mercury. Dental workers, including dentists, dental assistants, and dental hygienists, have been shown to have increased levels of mercury and suffer more from health issues related to mercury exposure than the general public. Mercury is known to be absorbed via inhalation or through the skin. There are many routine dental procedures that require the removal of dental amalgam by using the dental high-speed drill, which we suspected generates an occupational mercury exposure that is not sufficiently recognized. RESULTS: We showed that drilling dental amalgam generates particulate that volatilizes significant amounts of mercury vapor generally for more than an hour after removal. The levels of mercury vapor created by this procedure frequently exceed the safety thresholds of several jurisdictions and agencies. CONCLUSIONS: A significant, underrecognized source of localized exposure to mercury vapor was identified in this study. The vapor was created by microgram levels of particulate generated from dental amalgam removal with a high-speed dental drill, even when all feasible engineering controls were used to reduce mercury exposure. This exposure may explain why dental workers incur health effects when safety thresholds are not breached. The dispersion patterns for the particulate are not known, so the use of effective skin barriers and inhalation protection are required during amalgam removal to protect the dental worker from this form of occupational mercury exposure. Standard methodologies for occupational mercury exposure assessment appear to be inadequate when assessing mercury exposure during amalgam removal.

Venous thromboembolic disease after total hip and knee arthroplasty: current perspectives in a regulated environment.

Venous thromboembolic disease is the single most common reason for readmission to the hospital following total hip and total knee arthroplasty and remains a genuine threat to the life of the patient. Nevertheless, advances in surgical procedure, anesthetic management, and postoperative convalescence have altered the risks of venous thromboembolism after total joint arthroplasty in the lower extremity. Regional anesthetic techniques reduce the prevalence of venographic thrombosis by approximately 50%, and intraoperative monitoring has identified preparation of the femoral canal as the sentinel event that activates the coagulation cascade by the intravasation of marrow fat into the systemic circulation. Prevention of venographic thrombosis is most efficacious by administering fractionated heparin followed by warfarin; warfarin (international normalized ratio 2.0) appears to have a greater safety margin than fractionated heparin based on clinically meaningful bleeding events. Prevention of readmission events, proximal thrombosis, or pulmonary embolism has been demonstrated by using low-intensity warfarin. Aspirin, when used in conjunction with hypotensive epidural anesthesia after hip arthroplasty and regional anesthesia after knee arthroplasty, combined with pneumatic compression devices, also has been suggested to prevent clinical venous thromboembolism, as measured by readmission events. Oral thrombin inhibitors hold promise, but instances of liver toxicity have precluded approval in North America to date. Mechanical compression devices enhance venous flow and increase fibrinolytic activity in the lower extremity; clinical trials demonstrate efficacy in reducing venographic thrombosis alone after total knee arthroplasty and in combination with other chemoprophylactic agents after total hip arthroplasty. Extended chemoprophylaxis for 3 to 6 weeks after surgery is prudent in view of the protracted risk of thrombogenesis and the late occurrence of readmission for venous thrombosis and pulmonary embolism.

Sickness absence after carpal tunnel release: a systematic review of the literature.

Objectives The aim of this systematic review was to provide an overview of time to return to work (RTW) after carpal tunnel release (CTR), including return to different occupations and working patterns. Methods A systematic search from inception to 2016 was conducted using nine electronic databases, trial registries and grey literature repositories. Randomized controlled trials and observational studies reporting RTW times after CTR were included. Study risk of bias was assessed using Cochrane risk of bias assessment tools. Time to RTW was summarized using median and range. Results A total of 56 relevant studies were identified: 18 randomized controlled trials and 38 observational studies. Only 4 studies were rated as having a low risk of bias. Reported RTW times ranged from 4-168 days. Few studies reported occupational information. Among 6 studies, median time to return to non-manual work was 21 days (range 7-41), compared with 39 days for manual work (range 18-101). Median time to return to modified or full duties was 23 days (ranges 12-50 and 17-64, respectively), as reported by 3 studies. There was no common method of defining, collecting or reporting RTW data. Conclusions This review highlights wide variation in reported RTW times after CTR. Whilst occupational factors may play a role, these were poorly reported, and there is currently limited evidence to inform individual patients of their expected duration of work absence after CTR. A standardized definition of RTW is needed, as well as an agreed method of collecting and reporting related data.