Superconductivity beyond the Conventional Pauli Limit in High-Pressure CeSb_{2}.

We report the discovery of superconductivity at a pressure-induced magnetic quantum phase transition in the Kondo lattice system CeSb_{2}, sustained up to magnetic fields that exceed the conventional Pauli limit eightfold. Like CeRh_{2}As_{2}, CeSb_{2} is locally noncentrosymmetric around the Ce site, but the evolution of critical fields and normal state properties as CeSb_{2} is tuned through the quantum phase transition motivates a fundamentally different explanation for its resilience to applied field.

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.

Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol: a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults.

BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013.

Use of a national trauma registry to target violence reduction initiatives.

BACKGROUND: The incidence of interpersonal violence resulting in penetrating traumatic injury has increased in the UK. Violence reduction initiatives vary across the world, from reactive diversionary schemes to proactive educational intervention. To be successful a collaborative public health approach to violence reduction is vital. We examined regional data collected in a trauma network area as part of mandatory national trauma data submission to establish whether useful data could be extracted from this type of registry to inform regional violence reduction initiatives. Key information required to accurately target initiatives includes: who are the victims? where do incidents occur? and when do incidents occur? METHODS: Data were obtained from the national Trauma Audit and Research Network (TARN). This study utilised TARN inclusion criteria. Data for penetrating trauma patients from hospital sites in the Severn Major Trauma Network over an eight-year period were included in the analysis (1 June 2012 to 5 April 2020). The data were analysed using SPSS Statistics V27 and TARN analytics software. Existing ethical approval for anonymised registry data (PIAG section 60) was used. RESULTS: Over the eight-year study period, 299 cases of penetrating trauma were registered in the Major Trauma Network. Overall, the incidence of penetrating trauma is increasing (R value +0.470, and +0.900 when 2020 excluded). Male victims account for 87.3% of cases (n=261). Younger individuals are more likely to be victims of penetrating trauma. The proportion of victims aged 13-18 years increased from 0% in 2012 to 21.6% in 2019. There were 43 (14.3%) incidents of victims presenting more than once during the study period. The early evening and hour after midnight had the highest numbers of penetrating trauma incidents. Most incidents occurred in a small proportion of postcodes. All the postcodes identified as having high incidence of penetrating injuries were also areas with high deprivation. CONCLUSION: This study demonstrated that national trauma registry data can be used to establish valuable information about serious penetrating trauma in a region. This data provides key information with which to target a proactive approach to violence reduction in our region with implications for public health, police, and clinical policymakers.

One-year outcome of surgery compared with immobilization in a cast for adults with an undisplaced or minimally displaced scaphoid fracture : a meta-analysis of randomized controlled trials.

AIMS: There has been an increasing use of early operative fixation for scaphoid fractures, despite uncertain evidence. We conducted a meta-analysis to evaluate up-to-date evidence from randomized controlled trials (RCTs), comparing the effectiveness of the operative and nonoperative treatment of undisplaced and minimally displaced (≤ 2 mm displacement) scaphoid fractures. METHODS: A systematic review of seven databases was performed from the dates of their inception until the end of March 2021 to identify eligible RCTs. Reference lists of the included studies were screened. No language restrictions were applied. The primary outcome was the patient-reported outcome measure of wrist function at 12 months after injury. A meta-analysis was performed for function, pain, range of motion, grip strength, and union. Complications were reported narratively. RESULTS: Seven RCTs were included. There was no significant difference in function between the groups at 12 months (Hedges' g 0.15 (95% confidence interval -0.02 to 0.32); p = 0.082). The complication rate was higher in the operative group and involved more serious complications. CONCLUSION: We found no difference in functional outcome at 12 months for fractures of the waist of the scaphoid with ≤ 2 mm displacement treated operatively or nonoperatively. The complication rate was higher with operative treatment. Cite this article: Bone Joint J 2022;104-B(8):953-962.

Socially induced morphine pseudosensitization in adolescent mice.

Given that social influences are among the strongest predictors of adolescents' drug use, this study examined the effect of social interaction on morphine-induced hyperlocomotion in both adolescent and adult mice. Three experimental groups of adolescent and adult male mice were examined (i) morphine-treated mice (twice daily, 10-40 mg/kg, subcutaneous), (ii) saline-injected mice housed together with the morphine-treated mice ('saline cage-mates'), and (iii) saline-injected mice housed physically and visually separated from the morphine-treated mice ('saline alone'). After the treatment period, mice were tested individually for their locomotor response to 10 mg/kg morphine (subcutaneous). Adolescent saline cage-mates, though administered morphine for the very first time, exhibited an enhanced hyperlocomotion response similar to the locomotor sensitization response exhibited by the morphine-treated mice. This was not observed in adults. In adults, there were no significant differences in morphine-induced hyperlocomotion between saline alone and saline cage-mates. As expected, morphine-treated adults and adolescents both exhibited locomotor sensitization. These results show a vulnerability to social influences in adolescent mice, which does not exist in adult mice.

Surgical fixation compared with cast immobilisation for adults with a bicortical fracture of the scaphoid waist: the SWIFFT RCT.

BACKGROUND: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. Immediate surgical fixation of this fracture has increased. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of surgical fixation with cast treatment and early fixation in adults with scaphoid waist fractures that fail to unite. DESIGN: Multicentre, pragmatic, open-label, parallel two-arm randomised controlled trial with an economic evaluation and a nested qualitative study. SETTING: Orthopaedic departments of 31 hospitals in England and Wales recruited from July 2013, with final follow-up in September 2017. PARTICIPANTS: Adults (aged ≥ 16 years) presenting within 2 weeks of injury with a clear, bicortical fracture of the scaphoid waist on plain radiographs. INTERVENTIONS: Early surgical fixation using Conformité Européenne-marked headless compression screws. Below-elbow cast immobilisation for 6-10 weeks and urgent fixation of confirmed non-union. MAIN OUTCOME MEASURES: The primary outcome and end point was the Patient-Rated Wrist Evaluation total score at 52 weeks, with a clinically relevant difference of 6 points. Secondary outcomes included Patient-Rated Wrist Evaluation pain and function subscales, Short Form questionnaire 12-items, bone union, range of movement, grip strength, complications and return to work. RESULTS: The mean age of 439 participants was 33 years; 363 participants were male (83%) and 269 participants had an undisplaced fracture (61%). The primary analysis was on 408 participants with valid Patient-Rated Wrist Evaluation outcome data for at least one post-randomisation time point (surgery, n = 203 of 219; cast, n = 205 of 220). There was no clinically relevant difference in the Patient-Rated Wrist Evaluation total score at 52 weeks: the mean score in the cast group was 14.0 (95% confidence interval 11.3 to 16.6) and in the surgery group was 11.9 (95% confidence interval 9.2 to 14.5), with an adjusted mean difference of -2.1 in favour of surgery (95% confidence interval -5.8 to 1.6; p = 0.27). The non-union rate was low (surgery group, n = 1; cast group, n = 4). Eight participants in the surgery group had a total of 11 reoperations and one participant in the cast group required a reoperation for non-union. The base-case economic analysis at 52 weeks found that surgery cost £1295 per patient more (95% confidence interval £1084 to £1504) than cast treatment. The base-case analysis of a lifetime-extrapolated model confirmed that the cast treatment pathway was more cost-effective. The nested qualitative study identified patients' desire to have a 'sense of recovering', which surgeons should address at the outset. LIMITATION: There were 17 participants who had initial cast treatment and surgery for confirmed non-union, which in 14 cases was within 6 months from randomisation and in three cases was after 6 months. Three of the four participants in the cast group who had a non-union at 52 weeks were not offered surgery. CONCLUSIONS: Adult patients with an undisplaced or minimally displaced scaphoid waist fracture should have cast immobilisation and suspected non-unions immediately confirmed and urgently fixed. Patients should be followed up at 5 years to investigate the effect of partial union, degenerative arthritis, malunion and screw problems on their quality of life. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67901257. 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. 52. See the NIHR Journals Library website for further project information.

Fracture of the scaphoid bone (one of eight small bones in the wrist) is common in young active people. It is caused by a fall on the hand or the hand being suddenly forced backwards. The usual treatment is to rest the wrist in a plaster cast for 6­10 weeks and allow the broken bone to heal. In 1 in 10 cases in which the fracture is treated in a plaster cast, the bone does not heal and an operation is needed. In the operation, the broken bone is held still with a screw. In the last few years, it has become more common to fix the broken bone with a screw in the first few days after injury, instead of resting the wrist in a plaster cast. It is not clear if fixing the bone early with a screw, compared with resting the wrist in a cast, gives better outcomes for patients and if one treatment is better value for money for the NHS. In this study, 439 adult patients agreed either to have surgery to hold the broken scaphoid with a special screw or to have the wrist held still in a plaster cast (with surgery offered after 6 weeks to those who were still not healed). The decision about which treatment to use was made using randomisation, which is similar to tossing a coin. Patients reported their own wrist pain and function at 6, 12, 26 and 52 weeks. Information was also collected on general health, bone healing, grip strength and range of movement, complications from treatment and costs. No important differences were found in patients' wrist pain and function at 52 weeks. The bone did not heal properly in four patients in the surgery group or in nine patients in the plaster cast group at 52 weeks. For one of these patients in the surgery group and four of these patients in the plaster cast group, the bone did not join at all. Eight patients in the surgery group had further surgery following their initial operation to fix their wrist, and one patient in the cast group required repeated surgery because the bone did not join at all. The overall cost of treating with a plaster cast was lower than that of early surgery. Therefore, the findings of the study suggest that a plaster cast should be used initially and that the bone should be immediately fixed with a screw if it does not heal.

Extracellular signal-regulated kinase activation in the amygdala mediates elevated plus maze behavior during opioid withdrawal.

This study examined whether activation of extracellular signal-regulated kinase (ERK) contributes to the increased open-arm time observed in the elevated plus maze (EPM) during opioid withdrawal. We applied SL327, a selective ERK kinase (MEK) inhibitor, to specific limbic areas and examined the effect on EPM behaviors of controls and during naloxone-precipitated morphine withdrawal. We next confirmed that ERK activation increased in limbic areas of mice undergoing naloxone-precipitated morphine withdrawal. Direct injection of SL327 into the amygdala blocked the withdrawal-induced increase in open-arm time; however, injecting SL327 into the septum had no effect. Consistent with these results, both 0.2 and 2 mg/kg naloxone increased ERK activation in the central amygdala of morphine-dependent mice. In drug-naive mice, 2 mg/kg naloxone, but not 0.2 mg/kg, increased ERK activation in the central amygdala. During withdrawal, increased ERK activation was also observed in the lateral septum. In the locus coeruleus, a significant increase was observed only in morphine-dependent mice receiving 2 mg/kg, but not 0.2 mg/kg naloxone. In conclusion, ERK activation in limbic areas is likely involved in both the aversive properties of naloxone and in the affective/emotional symptoms of opioid withdrawal, including mediating EPM behaviors.

Different affective response to opioid withdrawal in adolescent and adult mice.

AIMS: Drug withdrawal is suggested to play a role in precipitating mood disorders in individuals with familial predisposition. Age-related differences in affective responses to withdrawal might explain the increased risk of mental illnesses when drug use begins during adolescence. Since there is a lack of animal research examining the effects of opioid withdrawal during adolescence, the present study examined whether there are age-related differences in affective responses to opioid withdrawal. MAIN METHODS: Adolescent and adult mice were injected with two different morphine regimens, namely low and high, which differed in the dosage. Three and nine days following discontinuation of morphine administration, immobility time in the forced swim test (FST) and locomotion (total distance traveled) were evaluated. KEY FINDINGS: On withdrawal day 3 (WD3), adolescent mice exhibited a decrease in immobility as compared to controls. No significant differences in immobility were observed on withdrawal day 9 (WD9). This effect on FST behaviors was not due to changes in overall motor activity, since no differences in locomotion were observed on either WD3 or WD9 in adolescent mice. In adults, no differences in either FST or locomotor behaviors were observed on WD3. As expected, on WD9, adult mice exhibited an increase in immobility and a decrease in locomotion. SIGNIFICANCE: This study demonstrates age-dependent differences in both FST scores and locomotor behaviors during opioid withdrawal. FST behaviors are classically used to evaluate mood in rodents, thus this study suggests that opioid withdrawal might affect mood differentially across age.

Increased elevated plus maze open-arm time in mice during naloxone-precipitated morphine withdrawal.

Opioid withdrawal is known to be anxiogenic in humans and, using the elevated plus maze (EPM), was demonstrated to also be anxiogenic in rats. Thus, this study characterizes EPM behaviors of mice during naloxone-precipitated morphine withdrawal. Naloxone did not significantly change EPM behaviors of drug-naïve mice. Additionally, morphine-dependent mice in which withdrawal was not precipitated (i.e. morphine-dependent mice receiving saline) spent less time in the open-arms compared to the controls. Surprisingly, increased open-arm time was observed in morphine-dependent mice undergoing naloxone-precipitated withdrawal. This increase was not because of total motor activity, as no significant differences in total activity were observed. Moreover, morphine dependency was necessary, given that there was not a significant increase in open-arm time for mice undergoing withdrawal from acute morphine. Increased open-arm time during withdrawal is unexpected, given that opioid withdrawal is usually associated with anxiety. Additionally, even in mice, naloxone-precipitated morphine withdrawal is known be aversive and increases plasma corticosterone levels. In conclusion, this study demonstrates somewhat unexpected EPM behavior in mice undergoing naloxone-precipitated morphine withdrawal. Possible interpretations of these EPM results, though somewhat speculative, raise the possibility that EPM behaviors might not be driven exclusively by anxiety levels but rather by other withdrawal-induced behaviors.

Comparison of Herbert and Acutrak screws in the treatment of scaphoid non-union and delayed union.

A retrospective analysis was performed on patients who had undergone surgery for delayed union or non-union of a scaphoid fracture. This was conducted to investigate if there was a difference in outcome between patients treated with the Acutrak screw or the Herbert screw. Twenty two cases were treated with a Herbert screw and 23 with an Acutrak screw. The patient demographics, aetiology of injury and fracture types were similar between the two groups. There was no significant difference in union rate or time to union for fractures treated with the Herbert screw or the Acutrak screw. There appears to be no difference in outcome for cases of scaphoid fracture delayed union and non-union treated with either the Herbert screw or the Acutrak screw.

Internal fixation of proximal humeral fractures.

We discuss the appropriate assessment and treatment options available for proximal humeral fractures. Important factors to consider are the fracture pattern, the bone quality and any co-morbidities. These are common injuries and are increasing in incidence due to an ageing population. The management of displaced 3- and 4-part fractures remains controversial. The ideal is anatomic reduction and stable internal fixation of the fractures especially the tuberosities to allow early mobilisation. The recent introduction of fixed angle locking plates allows stable fixation even in markedly osteoporotic bone. The early results are encouraging however there are presently no randomised trials comparing these devices to conservative treatment, conventional plating or hemiarthroplasty.

Oncogenic osteomalacia: localization of underlying peripheral mesenchymal tumors with use of Tc 99m sestamibi scintigraphy.

OBJECTIVE: To highlight a strategy for potential detection of mesenchymal tumors in oncogenic malacia, as illustrated by 3 cases. METHODS: Three case reports are presented in which successful localization of the offending neoplasm was accomplished by using whole-body Tc 99m sestamibi scanning. Alternative localization techniques are also reviewed. RESULTS: Oncogenic osteomalacia occurs infrequently and is caused by neoplasms that secrete phosphatonins, substances that interfere with proximal tubular resorption of phosphorus and can result in phosphaturia, hypophosphatemia, reduced 1,25-dihydroxyvitamin D concentration, and osteomalacia. Removal of the underlying neoplasm results in complete resolution of all biochemical, pathologic, and physical manifestations of this disorder, as shown in our 3 patients. Because the neoplasms are small and can occur in any tissue compartment, they are difficult to localize, a feature that often results in therapeutic failure. CONCLUSION: We conclude that use of whole-body Tc 99m sestamibi scanning may be an appropriate and cost-effective initial strategy for the localization of peripheral phosphatonin-secreting tumors.

The American College of Endocrinology and Endocrine University.

Subspecialty training in endocrinology depends in part on local expertise, with fellows having "hands-on" experience in some areas but only "book knowledge" in others. To provide more uniform training in new technologies, The American College of Endocrinology developed Endocrine University, which provides on-site didactic and interactive sessions on thyroid ultrasound, bone densitometry, and other topics over 6 to 7 days. The inaugural event in 2002 was attended by 137 fellows. A second conference in 2003 had capacity attendance of 143. A third course is scheduled for 2004. Fellows pay a token registration fee; the College provides grants to defray the cost of registration, travel, etc. Financial support comes from the College and industry, with plans for an endowment to sustain the program. Fellows value the educational sessions and also the unique opportunity to meet and visit with their peers. This innovative program can serve as a model for other specialties.

Osteomalacia after Roux-en-Y gastric bypass.

OBJECTIVE: To emphasize the potential for Roux-en-Y gastric bypass treatment of morbid obesity to result in late development of metabolic bone disease and to illustrate the error of treating a low bone mineral density with bisphosphonates in the presence of unrecognized osteomalacia. METHODS: We conducted a retrospective case review of clinical, laboratory, and radiologic details in a patient who underwent Roux-en-Y gastric bypass as well as a review of the literature relative to metabolic bone disease associated with bariatric surgical procedures. RESULTS: A 42-year-old woman was diagnosed with high bone turnover osteoporosis and failed to respond to bisphosphonate (alendronate) therapy. Her past medical history included corticosteroid-dependent asthma and a Roux-en-Y gastric bypass surgical procedure for obesity approximately 6 1/2 years before the current assessment. Evaluation revealed vitamin D deficiency in conjunction with pronounced secondary hyperparathyroidism and biochemical evidence of osteomalacia. Aggressive calcium and vitamin D supplementation corrected the vitamin D-deficient state and was accompanied by rapid improvement in clinical symptoms, biochemical variables, and bone mineral density. CONCLUSION: This case exemplifies two principles: (1) the potential for a Roux-en-Y gastric bypass surgical procedure to lead to the development of metabolic bone disease and (2) the importance of recognizing mineralization defects as a cause for low bone mineral density, before initiation of therapy with bisphosphonates.

Sex differences in affective response to opioid withdrawal during adolescence.

Drug withdrawal is suggested to play a role in precipitating mood disorders in individuals with familial predisposition. Age-related differences in affective responses to withdrawal might explain the increased risk of mental illnesses when drug use begins during adolescence. Recently we observed that, in contrast to adult male mice, adolescent males exhibited a decrease in immobility in the forced swim test on the third day of withdrawal, as compared with controls. Thus, the present study examined forced swim test behaviors of adolescent female mice during opioid withdrawal. Similar to the male study, adolescent female mice were injected with two morphine regimens which differed in dosage. Three and nine days following discontinuation of morphine administration, forced swim test immobility time and locomotion were evaluated. In contrast to males, which exhibited a decrease in immobility, no significant differences in immobility were observed in female adolescents undergoing withdrawal as compared with saline-injected controls. This sex difference in forced swim test behaviors was not due to changes in overall motor activity, since differences in locomotion were not observed in either male or female adolescent mice. Thus, this study demonstrates sex differences in forced swim test behavior during opioid withdrawal. Forced swim test behaviors are classically used to evaluate mood in rodents, thus this study suggests that opioid withdrawal might affect mood differentially across sexes.