Changing trends in the management of intertrochanteric hip fractures - a single centre experience

With an annual incidence greater than 65,000 in the UnitedKingdom, hip fractures are a common but debilitating injury predominantlyaffecting those over 65. Treatment is based on the anatomical location ofthe fracture relative to the capsule of the hip joint - fracturesoccurring within it are treated by arthroplasty, while extracapsularfractures are an indication for fixation. Intertrochanteric fractures arefurther grouped as stable (AO/OTA 31A1/A2) or unstable (31A3) which inturn governs in the current UK guidelines whether this fixation isachieved with a dynamic hip screw or intramedullary device. Anecdotally,some units are tending towards intramedullary devices for 31A2 fracturesas well, a practice which from the evidence does not appear to conferbenefit and carries an excess cost. We reviewed our data submitted to theNational Hip Fracture Database over the last five years and identifiedall intertrochanteric fractures, from which cohort we identified allpatients with 31A2 fractures by review of radiographs. The cohortcomprised 370 patients. We then recorded age, gender, ASA grade,abbreviated mental test score, residence from where admitted, length ofstay, destination on discharge and whether any further operations wererequired. There was no significant difference in the demographics of thegroups, year-on-year, except gender mix. There was a significant, twentyfoldrise in the use of intramedullary devices between 2011 and 2015.Length of stay, length of overall episode of care, revision rates,mortality and destination on discharge were unchanged. This use is notsupported by NICE guidelines and this study offers no evidence tocontradict this position. We advocate all centres examine their practiceto avoid a costly intervention without clinical benefit

Changing trends in the management of intertrochanteric hip fractures - a single centre experience

With an annual incidence greater than 65,000 in the UnitedKingdom, hip fractures are a common but debilitating injury predominantlyaffecting those over 65. Treatment is based on the anatomical location ofthe fracture relative to the capsule of the hip joint - fracturesoccurring within it are treated by arthroplasty, while extracapsularfractures are an indication for fixation. Intertrochanteric fractures arefurther grouped as stable (AO/OTA 31A1/A2) or unstable (31A3) which inturn governs in the current UK guidelines whether this fixation isachieved with a dynamic hip screw or intramedullary device. Anecdotally,some units are tending towards intramedullary devices for 31A2 fracturesas well, a practice which from the evidence does not appear to conferbenefit and carries an excess cost. We reviewed our data submitted to theNational Hip Fracture Database over the last five years and identifiedall intertrochanteric fractures, from which cohort we identified allpatients with 31A2 fractures by review of radiographs. The cohortcomprised 370 patients. We then recorded age, gender, ASA grade,abbreviated mental test score, residence from where admitted, length ofstay, destination on discharge and whether any further operations wererequired. There was no significant difference in the demographics of thegroups, year-on-year, except gender mix. There was a significant, twentyfoldrise in the use of intramedullary devices between 2011 and 2015.Length of stay, length of overall episode of care, revision rates,mortality and destination on discharge were unchanged. This use is notsupported by NICE guidelines and this study offers no evidence tocontradict this position. We advocate all centres examine their practiceto avoid a costly intervention without clinical benefit

The reinforcement sensitivity theory of personality in children: A new questionnaire

We report the development of a self-report questionnaire of the reinforcement sensitivity theory (RST) of personality for use with children. Focus groups were held with children to sample their experiences of situations modelled on components of three RST systems: fight-flight-freeze system (FFFS, related to fear), behavioural inhibition system (BIS, related to anxiety), and behavioural approach system (BAS, related to approach). The thematic responses formed the conceptual anchors to the development of test items that were examined using exploratory factor analysis in a sample of 288 9–13 year olds. After eliminating items that did not load on their designated factor, or substantially cross-loaded over factors, the original 48 items were reduced to 21 items: 7 items for each of the BIS, FFFS and BAS factors. The separation of the BIS and FFFS items across two factors is consistent with the revised model of RST. We offer this new questionnaire as a RST measure of fundamental motivation and emotion traits in children

Patient, hospital and environmental costs of unnecessary bloodwork : capturing the triple bottom line of inappropriate care in general surgery patients

Objective: To characterise the extent of unnecessary care in general surgery inpatients using a triple bottom line approach. Design: Patients with uncomplicated acute surgical conditions were retrospectively evaluated for unnecessary bloodwork according to the triple bottom line, quantifying the impacts on patients, healthcare costs and greenhouse gas emissions. The carbon footprint of common laboratory investigations was estimated using PAS2050 methodology, including emissions generated from the production, transport, processing and disposal of consumable goods and reagents. Setting: Single-centre tertiary care hospital. Participants: Patients admitted with acute uncomplicated appendicitis, cholecystitis, choledocholithiasis, gallstone pancreatitis and adhesive small bowel obstruction were included in the study. 304 patients met inclusion criteria and 83 were randomly selected for in-depth chart review. Main outcome measures: In each patient population, the extent of over-investigation was determined by comparing ordered laboratory investigations against previously developed consensus recommendations. The quantity of unnecessary bloodwork was measured by number of phlebotomies, tests and blood volume in addition to healthcare costs and greenhouse gas emissions. Results: 76% (63/83) of evaluated patients underwent unnecessary bloodwork resulting in a mean of 1.84 phlebotomies, 4.4 blood vials, 16.5 tests and 18 mL of blood loss per patient. The hospital and environmental cost of these unnecessary activities was $C5235 and 61 kg CO2e (974 g CO2e per person), respectively. The carbon footprint of a common set of investigations (complete blood count, differential, creatinine, urea, sodium, potassium) was 332 g CO2e. Adding a liver panel (liver enzymes, bilirubin, albumin, international normalised ratio/partial thromboplastin time) resulted in an additional 462 g CO2e. Conclusions: We found considerable overuse of laboratory investigations among general surgery patients admitted with uncomplicated acute surgical conditions resulting in unnecessary burden to patients, hospitals and the environment. This study identifies an opportunity for resource stewardship and exemplifies a comprehensive approach to quality improvement

Identification of genes associated with dissociation of cognitive performance and neuropathological burden: Multistep analysis of genetic, epigenetic, and transcriptional data

Introduction: The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation. Methods and findings: “Residual cognition” was quantified by regressing out the effects of cerebral pathologies and demographic characteristics on global cognitive performance proximate to death. To identify genes influencing residual cognition, we leveraged neuropathological, genetic, epigenetic, and transcriptional data available for deceased participants of the Religious Orders Study (n = 492) and the Rush Memory and Aging Project (n = 487). Given that our sample size was underpowered to detect genome-wide significance, we applied a multistep approach to identify genes influencing residual cognition, based on our prior observation that independent genetic and epigenetic risk factors can converge on the same locus. In the first step (n = 979), we performed a genome-wide association study with a predefined suggestive p < 10−5, and nine independent loci met this threshold in eight distinct chromosomal regions. Three of the six genes within 100 kb of the lead SNP are expressed in the dorsolateral prefrontal cortex (DLPFC): UNC5C, ENC1, and TMEM106B. In the second step, in the subset of participants with DLPFC DNA methylation data (n = 648), we found that residual cognition was related to differential DNA methylation of UNC5C and ENC1 (false discovery rate < 0.05). In the third step, in the subset of participants with DLPFC RNA sequencing data (n = 469), brain transcription levels of UNC5C and ENC1 were evaluated for their association with residual cognition: RNA levels of both UNC5C (estimated effect = −0.40, 95% CI −0.69 to −0.10, p = 0.0089) and ENC1 (estimated effect = 0.0064, 95% CI 0.0033 to 0.0096, p = 5.7 × 10−5) were associated with residual cognition. In secondary analyses, we explored the mechanism of these associations and found that ENC1 may be related to the previously documented effect of depression on cognitive decline, while UNC5C may alter the composition of presynaptic terminals. Of note, the TMEM106B allele identified in the first step as being associated with better residual cognition is in strong linkage disequilibrium with rs1990622A (r2 = 0.66), a previously identified protective allele for TDP-43 proteinopathy. Limitations include the small sample size for the genetic analysis, which was underpowered to detect genome-wide significance, the evaluation being limited to a single cortical region for epigenetic and transcriptomic data, and the use of categorical measures for certain non-amyloid-plaque, non-neurofibrillary-tangle neuropathologies. Conclusions: Through a multistep analysis of cognitive, neuropathological, genomic, epigenomic, and transcriptomic data, we identified ENC1 and UNC5C as genes with convergent genetic, epigenetic, and transcriptomic evidence supporting a potential role in the dissociation of cognition and neuropathology in an aging population, and we expanded our understanding of the TMEM106B haplotype that is protective against TDP-43 proteinopathy

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population