Why medical students choose not to carry out an intercalated BSc : a questionnaire study.

Peer reviewedPublisher PD

Nonunion of the clavicle: novel use of clinical recovery and ultrasound to improve our ability to predict fracture healing

The aim of this thesis was to progress our understanding of clavicle nonunion and the ability to accurately predict fracture healing in order to improve the current management of these injuries. Although only one in seven fractures go onto nonunion, these are challenging to predict. It is unclear if the recent widespread increase in the use of acute plate fixation for displaced fractures is justified on current evidence. It is unknown whether the early accurate prediction of fractures at high risk of nonunion is advantageous. Currently the perceived risk of nonunion is largely based on factors available at time of injury alone. The evaluation of clinical recovery following non-operative management and the novel use of ultrasound may advance our ability to accurately predict fracture healing for these injuries. The cost-effectiveness of acute clavicle plate fixation versus non-operative treatment was estimated from randomized controlled trial data that had been previously published. This was completed prior to the start of this thesis and the author was not involved in the original trial. A large retrospective review of clavicle fracture fixations was undertaken to determine whether delayed clavicle fixation has an increased risk of complications compared to acute operative management. A prospective study of displaced midshaft fractures was carried out over a two-year period to determine the influence of functional recovery on the ability to predict fracture healing. The influence of clavicle fracture management on the early functional recovery was evaluated with data from a randomized controlled trial and second prospective cohort. Finally, the novel use of ultrasound to detect early callus formation and determine whether this allows accurate prediction of fracture healing was evaluated for a cohort of clavicle and tibia fractures. The estimated cost per quality-of-life adjusted year of acute plate fixation over non-operative treatment is £480,309.41/QALY. For a threshold of £20,000/QALY the benefit of acute fixation would need to be present for 24 years to be cost-effective over conservative treatment. Linear regression analysis identified nonunion as the only factor to negatively influence the SF-6D at 12-months (p<0.001). A ten-year cohort of 259 clavicle plate fixations found failed primary surgery requiring revision fixation occurred in 7.7% of all patients. Smoking (p<0.001), presence of a post-operative infection (<0.001), increasing age (p=0.018), and greater time delay from injury to surgery (p=0.015) was identified as significant independent predictors on regression analysis. Receiver operating curve analysis (ROC) revealed that surgery beyond 96 days from injury has an increased rate of major complications and revision surgery. Using a matched case cohort of cases before (n=67) and after the ‘safe window’ (n=77), the risk of post-operative infection increased (Odds ratio (OR) 7.7, p=0.028), fixation failure (OR 3.8, p=0.017) and revision surgery (OR 4.8 p=0.004). A delay to operative fixation beyond 3 months following injury would appear to be associated with an increased risk of major operative complications and revision surgery. A large prospective cohort of 200 patients managed non-operatively with a displaced midshaft clavicle fracture were recruited. Regression modelling found a QuickDASH ≥40 (p=0.001), no callus on radiograph (p=0.004) and fracture movement on examination (p=0.001) were significant predictors of nonunion. If none were present the predicted nonunion risk was 3%, found in 40% of the cohort. Conversely if two or more of the predictors were present, found in 23.5% of the cohort, the predicted nonunion risk was 60%. The delayed assessment nonunion model appeared to have superior accuracy when compared to the estimation of nonunion at time of injury alone healing on ROC curve analysis (Area Under Curve analysis; 87.3% vs 64.8% respectively). Data from a randomized controlled trial was used to compare 86 patients who underwent operative fixation against 76 patients that united with non-operative treatment. The recovery of normal shoulder function, as defined by a DASH score within the predicted 95% confidence interval for each respective patient was similar between each group at six-weeks (operative 26.7% vs non-operative 25.0%, p=0.80), three-months (52.3% vs 44.2%, p=0.77) and six-months post-injury (86.0% vs 90.8%, p=0.35). The mean DASH score and return to work was also comparable at each time point. Regression analysis found no specific patient, injury or fracture predictor was associated with an early return of function following non-operative management at six or twelve weeks. From a pilot study of twenty clavicle fractures, six-week sonographic bridging callus appeared to be the most accurate, and repeatable, predictor of fracture healing with a strong agreement on intra class correlation (ICC) between four reviewers (ICC 0.82, 95% confidence interval 0.68-0.91). In a large prospective study of 112 patients, sonographic bridging callus was detected in 62.5% (n=70/112) of the cohort at six weeks post-injury. If present, union occurred in 98.6% of the fractures (n=69/70). If absent, nonunion developed in 40.5% of cases (n=17/42). The sensitivity to predict union with sonographic bridging callus at six weeks was 73.4% and the specificity was 94.4%. Three-dimensional fracture reconstruction can be created using multiple ultrasound images in order to evaluate the presence of bridging callus. This imaging modality has the potential to enhance the usability and accuracy of identification of fracture healing at an early stage following injury. Nonunion following a displaced midshaft clavicle fractures accounts for the majority of poor functional recovery and impaired quality of life over the first-year post-injury. Prediction of clavicle fracture healing at six weeks following injury maybe a safe and effective strategy to identify patients at greatest risk of nonunion. The use of functional recovery enables a more accurate estimation of nonunion risk compared to conventional prediction at time of injury alone. The use of ultrasound may further refine our ability to predict fracture healing

A Boron–Boron Double Transborylation Strategy for the Synthesis of gem-Diborylalkanes

Olefin hydroboration reactions provide efficient access to synthetically versatile and easily handled organoboronic esters. In this study, we demonstrate that the commercially available organoborane reagent 9-borabicyclo[3.3.1]nonane (H-B-9-BBN) can serve as a catalyst for the sequential double hydroboration of alkynes using pinacolborane (HBpin). This strategy, which is effective for a wide range of terminal alkynes, is predicated upon a key C(sp3)-B/B-H transborylation reaction. Transition-state thermodynamic parameters and 10-boron-isotopic labeling experiments are indicative of a σ-bond metathesis exchange pathway

Continuous flow mechanochemistry: reactive extrusion as an enabling technology in organic synthesis

Rapid and wide-ranging developments have established mechanochemistry as a powerful avenue in sustainable organic synthesis. This is primarily due to unique opportunities which have been offered in solvent-free - or highly solvent-minimised - reaction systems. Nevertheless, despite elegant advances in ball-milling technology, limitations in scale-up still remain. This tutorial review covers the first reports into the translation from "batch-mode" ball-milling to "flow-mode" reactive extrusion, using twin-screw extrusion

The Olympia anatomic polished cemented stem is associated with a high survivorship, excellent hip-specific functional outcome, and high satisfaction levels:follow-up of 239 consecutive patients beyond 15 years

Introduction: The Olympia femoral stem is a stainless steel, anatomically shaped, polished and three-dimensionally tapered implant designed for use in cemented total hip arthroplasty (THA). The primary aim of this study was to determine the long-term survivorship, radiographic outcome, and patient-reported outcome measures (PROMs) of the Olympia stem. Patients and methods: Between May 2003 and December 2005, 239 patients (264 THAs) underwent a THA with an Olympia stem in our institution. Patient-reported outcome measures were assessed using the Oxford Hip Score (OHS), EuroQol-5 dimensions (EQ-5D) score, and patient satisfaction at mean 10 years following THA. Patient records and radiographs were then reviewed at a mean of 16.5 years (SD 0.7, 15.3–17.8) following THA to identify occurrence of complications or revision surgery for any cause following surgery. Radiographs were assessed for lucent lines and lysis according to Gruen’s zones Results: Mean patient age at surgery was 68.0 years (SD 10.9, 31–93 years). There were 156 women (65%, 176 THAs). Osteoarthritis was the indication for THA in 204 patients (85%). All cause stem survivorship at 10 years was 99.2% (95% confidence interval [CI], 97.9%–100%) and at 15 years was 97.5% (94.6%–100%). The 15-year stem survival for aseptic loosening was 100%. Analysis of all-cause THA failure demonstrated a survivorship of 98.5% (96.3%–100%) at 10 years and 95.9% (92.4%–99.4%) at 15 years. There were 9 THAs with non-progressive lucent lines in a single Gruen zone and 3 had lines in two zones, and no patient demonstrated signs for lysis. At a mean of 10-year (SD 0.8, 8.7–11.3) follow-up, mean OHS was 39 (SD 10.3, range 7–48) and 94% of patients reported being very satisfied or satisfied with their THA. Conclusions: The Olympia stem demonstrated excellent 10-year PROMs and very high rates of stem survivorship at final follow-up beyond 15 years

3D ultrasound reconstruction of sonographic callus:a novel imaging modality for early evaluation of fracture healing

AIMS: The aim of this study was to establish a reliable method for producing 3D reconstruction of sonographic callus. METHODS: A cohort of ten closed tibial shaft fractures managed with intramedullary nailing underwent ultrasound scanning at two, six, and 12 weeks post-surgery. Ultrasound capture was performed using infrared tracking technology to map each image to a 3D lattice. Using echo intensity, semi-automated mapping was performed to produce an anatomical 3D representation of the fracture site. Two reviewers independently performed 3D reconstructions and kappa coefficient was used to determine agreement. A further validation study was undertaken with ten reviewers to estimate the clinical application of this imaging technique using the intraclass correlation coefficient (ICC). RESULTS: Nine of the ten patients achieved union at six months. At six weeks, seven patients had bridging callus of ≥ one cortex on the 3D reconstruction and when present all achieved union. Compared to six-week radiographs, no bridging callus was present in any patient. Of the three patients lacking sonographic bridging callus, one went onto a nonunion (77.8% sensitive and 100% specific to predict union). At 12 weeks, nine patients had bridging callus at ≥ one cortex on 3D reconstruction (100%-sensitive and 100%-specific to predict union). Presence of sonographic bridging callus on 3D reconstruction demonstrated excellent reviewer agreement on ICC at 0.87 (95% confidence interval 0.74 to 0.96). CONCLUSION: 3D fracture reconstruction can be created using multiple ultrasound images in order to evaluate the presence of bridging callus. This imaging modality has the potential to enhance the usability and accuracy of identification of early fracture healing. Cite this article: Bone Joint Res 2021;10(12):759–766

Acute plate fixation of displaced midshaft clavicular fractures is not associated with earlier return of normal shoulder function when union is achieved

Aims: It is unclear whether acute plate fixation facilitates earlier return of normal shoulder function following a displaced mid-shaft clavicular fracture compared with nonoperative management when union occurs. The primary aim of this study was to establish whether acute plate fixation was associated with a greater return of normal shoulder function when compared with nonoperative management in patients who unite their fractures. The secondary aim was to investigate whether there were identifiable predictors associated with return of normal shoulder function in patients who achieve union with nonoperative management. Methods: Patient data from a randomized controlled trial were used to compare acute plate fixation with nonoperative management of united fractures. Return of shoulder function was based on the age- and sex-matched Disabilities of the Arm, Shoulder and Hand (DASH) scores for the cohort. Independent predictors of an early recovery of normal shoulder function were investigated using a separate prospective series of consecutive nonoperative displaced mid-shaft clavicular fractures recruited over a two-year period (aged ≥ 16 years). Patient demographics and functional recovery were assessed over the six months post-injury using a standardized protocol. Results: Data from the randomized controlled trial consisted of 86 patients who underwent operative fixation compared with 76 patients that united with nonoperative treatment. The recovery of normal shoulder function, as defined by a DASH score within the predicted 95% confidence interval for each respective patient, was similar between each group at six weeks (operative 26.7% vs nonoperative 25.0%, p = 0.800), three months (52.3% vs 44.2%, p = 0.768), and six months post-injury (86.0% vs 90.8%, p = 0.349). The mean DASH score and return to work were also comparable at each timepoint. In the prospective cohort, 86.5% (n = 173/200) achieved union by six months post-injury (follow-up rate 88.5%, n = 200/226). Regression analysis found that no specific patient, injury, or fracture predictor was associated with an early return of function at six or 12 weeks. Conclusion: Return of normal shoulder function was comparable between acute plate fixation and nonoperative management when union was achieved. One in two patients will have recovery of normal shoulder function at three months, increasing to nine out of ten patients at six months following injury when union occurs, irrespective of initial treatment

A ball-milling-enabled cross-electrophile coupling

The nickel-catalyzed cross-electrophile coupling of aryl halides and alkyl halides enabled by ball-milling is herein described. Under a mechanochemical manifold, the reductive C–C bond formation was achieved in the absence of bulk solvent and air/moisture sensitive setups, in reaction times of 2 h. The mechanical action provided by ball milling permits the use of a range of zinc sources to turnover the nickel catalytic cycle, enabling the synthesis of 28 cross-electrophile coupled products