Outcomes of total hip and knee arthroplasty in patients with haemophilia: A meta-analysis of comparative studies and clinical practice recommendations.

AIM: We aimed to compare the outcomes of total hip and knee arthroplasty (THA, TKA) in haemophilic patients compared to matched controls. METHODS: Through a literature search we identified all cohort studies comparing perioperative complications and other outcomes of THA and TKA in haemophilic patients and matched controls without haemophilia. Results of the same outcome measure assessed by two or more studies were pooled in meta-analyses; odds ratios (ORs) with 95% confidence intervals (CI) were calculated. The risk of bias in included studies and certainty of evidence of each result were assessed using the Newcastle-Ottawa scale and the GRADE tool respectively. RESULTS: A total of five retrospective studies with matched controls were included; four of them were of good and one of fair quality. Based on moderate certainty evidence, compared to matched controls, patients with haemophilia had a significantly higher incidence of the following complications after a) TKA: periprosthetic joint infection [PJI; OR 1.6 CI (1.3, 1.9)], 1-year revision/re-operation [OR 1.4 CI (1.2, 1.8)] and b) THA: major and minor 90-day complications [major OR 2.2 CI (1.7, 2.9); minor OR 1.4 CI (1.1, 1.8)], venous thromboembolism [OR 3.1 CI (2.1, 4.6)]. PJI incidence in THA was not different in haemophilia compared to controls [OR 1.5 CI (.9, 2.6)]. CONCLUSION: Our results can be used by healthcare professionals counselling patients with haemophilia considering a THA or TKA as part of the informed consent process. We provide detailed clinical recommendations for the perioperative management of THA and TKA in haemophilic patients.

Patient-Reported Outcomes After Switching to a 2-Drug Regimen of Fixed-Dose Combination Dolutegravir/Lamivudine: 48-Week Results from the SALSA Study.

Patient-reported outcomes (PROs) facilitate communication between patients and providers, enhancing patient-centered care. We report PROs for virologically suppressed people living with HIV-1 who switched to dolutegravir/lamivudine (DTG/3TC) or continued their 3- or 4-drug current antiretroviral regimen (CAR) in the phase 3 SALSA study. Secondary endpoints included change from baseline in HIV Treatment Satisfaction Questionnaire (status version; HIVTSQs) and HIV Symptom Distress Module (HIV-SDM) at Weeks 4, 24, and 48. A post hoc analysis assessed change in HIVTSQs and HIV-SDM by age (≥ 50 and < 50 years). Higher HIVTSQs scores represent greater treatment satisfaction (range, 0-60); lower HIV-SDM scores indicate less symptom bother (range, 0-80). Participants in the DTG/3TC (n = 246) and CAR (n = 247) groups reported comparable baseline HIVTSQs total scores (mean [SD], 55.2 [6.5] and 55.8 [5.5], respectively). Beginning at Week 4, mean HIVTSQs scores in the DTG/3TC group further increased vs. CAR and were sustained through Week 48. Baseline mean (SD) HIV-SDM symptom bother scores were comparable between the DTG/3TC (9.0 [9.9]) and CAR (7.9 [9.3]) groups. Small improvements in HIV-SDM scores favoring DTG/3TC were observed at Weeks 4 and 24 and sustained through Week 48 (though not significant between groups). Participants aged ≥ 50 and < 50 years who switched to DTG/3TC reported higher satisfaction and less symptom distress vs. CAR; these results were generally comparable between age groups. Participants who switched to DTG/3TC reported rapid and sustained improvements in treatment satisfaction compared with those who continued CAR, reinforcing the benefits of DTG/3TC beyond virologic suppression (NCT04021290; registration date, 7/11/2019).

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies.

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Exercise Capacity and Reoperation Late After Transatrial Fallot Repair.

BACKGROUND: The exercise capacity long after repair of tetralogy of Fallot, when performed exclusively with a transatrial repair, is unclear. It is also unknown whether echocardiography and cardiopulmonary exercise testing can predict the risk of reoperation in this patient group. METHOD: We retrospectively reviewed the clinical records of 59 patients who underwent cardiopulmonary exercise testing after transatrial Fallot repair at a single centre. Patients underwent cardiopulmonary exercise testing at a mean age of 16.6±4.4 years, and at 15.3±4.1 years after Fallot repair. RESULTS: At testing, the volume of oxygen consumption at maximal exercise (VO2 max) was 71%±13% and the oxygen pulse was 80%±17% of predicted values. Seventeen (17) patients (29%) had a VO2 max superior to 80% of the predicted value. Thirty-two (32) patients (56%) had severe pulmonary regurgitation, three (5%) had moderate pulmonary regurgitation, and 12 (21%) had mild pulmonary regurgitation. After a mean of 7.8±3.9 years following cardiopulmonary exercise testing (23±5.3 years after the repair), 21 (40%) patients underwent reoperation. Right ventricular dilation and systolic function on echocardiography were both significantly associated with subsequent reoperation rates. Patients who had severe right ventricular dilation were eight times more likely to undergo subsequent reoperation (hazard ratio 8.67; 1.82-41.3; p=0.007). No cardiopulmonary exercise testing variable independently predicted reoperation. CONCLUSIONS: The exercise capacity at adolescence following transatrial repair of tetralogy of Fallot is maintained at around 70% of predicted values. Only the patients with normal right ventricular size and normal right ventricular function seemed to be protected from reoperation over the subsequent decade. We found no exercise variables which predicted reoperation.

No advantage with navigated versus conventional mechanically aligned total knee arthroplasty-10 year results of a randomised controlled trial.

PURPOSE: Computer-assisted surgery (CAS) total knee arthroplasty (TKA) remains a controversial area of surgical practice. The aim of this study is to report the ten-year revision rates and patient-reported outcome measures (PROMS) of a single-blinded, prospective, randomised controlled trial comparing electromagnetically (EM) navigated and conventional TKA. METHODS: 199 patients were randomised to receive either EM navigated or conventional TKA where the aim of implantation was neutral mechanical alignment in all cases. Ten-year revision rates were collated and compared between the two intervention groups. Longitudinal PROMS data was collected prospectively at various time points up to 10 years post-operatively. RESULTS: Over the ten-year period, there were 23 deaths (22.8%) in the EM navigation cohort and 30 deaths (30.6%) in the conventional cohort. At 10 years post-operatively, there was no statistically significant difference in all cause revision between the EM navigation and conventional cohort (4.0 vs 6.1%, p = 0.429). When analysing causes of revision that might be influenced by utilising EM navigation, there was no statistically significant difference in revisions (3.0% EM navigated vs 4.1% conventional group, p = 0.591). Patients that received navigated TKAs had improved Oxford Knee Society, American Knee Society Score and range of motion at 3 months following surgery compared to conventional TKA (p = 0.002, p = 0.032, and p = 0.05, respectively). However, from 1 to 10 years post-operatively, both interventions had equivalent outcomes. CONCLUSION: There is no difference in revision rates or clinical outcomes comparing EM navigated versus conventional TKA at ten-year follow-up. The expected mortality rate makes it unlikely that a difference in revision rates will reach statistical significance in the future. In the setting of an experienced knee arthroplasty surgeon, it is difficult to justify the additional costs of CAS in TKA surgery. LEVEL OF EVIDENCE: I.

Ethical Issues in Research: Perceptions of Researchers, Research Ethics Board Members and Research Ethics Experts.

In the context of academic research, a diversity of ethical issues, conditioned by the different roles of members within these institutions, arise. Previous studies on this topic addressed mainly the perceptions of researchers. However, to our knowledge, no studies have explored the transversal ethical issues from a wider spectrum, including other members of academic institutions as the research ethics board (REB) members, and the research ethics experts. The present study used a descriptive phenomenological approach to document the ethical issues experienced by a heterogeneous group of Canadian researchers, REB members, and research ethics experts. Data collection involved socio-demographic questionnaires and individual semi-structured interviews. Following the triangulation of different perspectives (researchers, REB members and ethics experts), emerging ethical issues were synthesized in ten units of meaning: (1) research integrity, (2) conflicts of interest, (3) respect for research participants, (4) lack of supervision and power imbalances, (5) individualism and performance, (6) inadequate ethical guidance, (7) social injustices, (8) distributive injustices, (9) epistemic injustices, and (10) ethical distress. This study highlighted several problematic elements that can support the identification of future solutions to resolve transversal ethical issues in research that affect the heterogeneous members of the academic community.

Double lesion MRgFUS treatment of essential tremor targeting the thalamus and posterior sub-thalamic area: preliminary study with two year follow-up.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) is an effective treatment for essential tremor (ET). However, the optimal intracranial target sites remain to be determined. OBJECTIVE: To assess MRgFUS induced sequential lesions in (anterior-VIM/VOP nuclei) the thalamus and then posterior subthalamic area (PSA) performed during the same procedure for alleviating ET. METHODS: 14 patients had unilateral MRgFUS lesions placed in anterior-VIM/VOP then PSA. Bain-Findley Spirals were collected during MRgFUS from the treated arm (BFS-TA) and throughout the study from the treated (BFS-TA) and non-treated (BFS-NTA) arms and scored by blinded assessors. Although, the primary outcome was change in the BFS-TA from baseline to 12 months we have highlighted the 24-month data. Secondary outcomes included the Clinical Rating Scale for Tremor (CRST), Quality of Life for ET (QUEST) and PHQ-9 depression scores. RESULTS: The mean improvement in the BFS-TA from baseline to 24 months was 41.1% (p < 0.001) whilst BFS-NTA worsened by 8.8% (p < 0.001). Intra-operative BFS scores from the targeted arm showed a mean 27.9% (p < 0.001) decrease after anterior-VIM/VOP ablation and an additional 30.1% (p < 0.001) reduction from post anterior-VIM/VOP to post-PSA ablation. Mean improvements at 24 month follow-up in the CRST-parts A, B and C were 60.7%, 30.4% and 65.6% respectively and 37.8% in QUEST-tremor score (all p < 0.05). Unilateral tremor severity scores decreased in the treated arm (UETTS-TA) 72.9% (p = 0.001) and non-treated arm (UETTS-NTA) 30.5% (p = 0.003). At 24 months residual adverse effects were slight unsteadiness (n = 1) and mild hemi-chorea (n = 1). CONCLUSION: Unilateral anterior-VIM/VOP and PSA MRgFUS significantly diminished contralateral arm tremor with improvements in arm function, tremor related disability and quality of life, with an acceptable adverse event profile.

Soft-tissue landmarks for tibial baseplate rotational alignment in total knee arthroplasty: A cadaveric study.

The tip of the tibial tubercle (TTT) is used to assess tibial baseplate rotation in total knee arthroplasty (TKA); however, it can be difficult to palpate and visualize intraoperatively. Several more easily accessible soft-tissue structures have been proposed as intraoperative assessments, including the patellar tendon's medial border (MBPT) and the junction of the medial third of the patellar tendon (mt-PT). No studies have described the relationship between the TTT and these proposed landmarks. The aims of the study were to (1) determine the relationship of the soft-tissue landmarks to the TTT and (2) identify any sex differences in these measures. Measurements of the position of these soft-tissue landmarks relative to the TTT were made on 56 cadaveric knees (28 female) by two observers at the level of the standard tibial cut (10 mm distal to the lateral tibial plateau). The results obtained were compared by sex and side. On average, 50.7% (SD 6.79, range 33.1%-63.1%) of the patellar tendon footprint was medial to the TTT. There were no significant differences between the sexes or left and right lower limbs. However, there was large variability in the position of all the soft-tissue landmarks relative to the TTT. The results indicate that, on average, the patellar tendon footprint is evenly spread around the TTT. However, there is a large variability in the anatomical relationship between the soft-tissue landmarks and the TTT. Caution is advised if relying on these structures intraoperatively.

Alumina ceramic-on-ceramic hybrid total hip arthroplasty. A median of 15 years follow-up.

INTRODUCTION: The optimum choice of bearing surfaces in total hip replacement (THR) in the younger and active patient remains controversial. The aim of this study was to report the 10 year clinical outcomes, and a median of 15 year implant survival and incidence of complications in a series of Alumina ceramic-on-ceramic THRs utilising an uncemented shell and cemented stem. METHODS: From January 2004 to December 2007, 175 consecutive patients (195 hips) underwent primary THR. The acetabular components was Trident Peripheral Self Locking (Stryker Orthopaedics) with a third-generation ceramic head and liner (Alumina ceramic, Stryker Orthopaedics). The stem utilised was an Exeter V-40 (Stryker Orthopaedics). Data were collated on demographics, surgical factors, clinical outcomes, radiographic outcomes and revision. RESULTS: 23 patients (27 THRs) died during the follow-up period at a median of 7.8 (3.8 to 9.0) years post-operatively due to causes unrelated to the THR. Median age at time of surgery was 55 (interquartile range 48-60) years. Median follow-up for surviving patients was 15.2 years. Survivorship for all-cause revision was 97.2%. Increasing patient age at time of surgery was associated with a higher OHS at 10 years (p = 0.022). 32 mm head diameter had an improved OHS at 3 months (p = 0.014) and 10 years (p = 0.030). Posterior surgical approach had a statistically significant better OHS at 3 months (p = 0.015) and 1 year (p < 0.001), but the effect was not significant at 10 years (p = 0.440). CONCLUSION: The findings of this study support excellent long-term outcomes and survivorship of Alumina ceramic-on-ceramic bearing in a hybrid THR in a younger population. Surgical factors leading to a more favourable outcome were the use of a 32 mm femoral head and a posterior approach. Increasing age at surgery demonstrated the most sustained improvement in 10 year clinical outcomes.

Electromagnetic Navigated Versus Conventional Total Knee Arthroplasty-A Five-Year Follow-Up of a Single-Blind Randomized Control Trial.

BACKGROUND: The objective of this study is to provide the 5-year follow-up results of a randomized study comparing conventional versus electromagnetic computer navigated total knee arthroplasty. METHODS: Analysis of 127 patients (66 navigated and 61 conventional surgeries) was performed from a prospective, single-blinded, randomized controlled trial. Patient-reported outcome measures were collected at 5 years after surgery and compared with previously published 1-year clinical outcomes. Five-year surgical revision rates were collated and compared between intervention groups. RESULTS: Overall, there have been continued improvements in the clinical scores of patients in both groups when compared with clinical data at 1 year; however, at 5 years, there is no statistical difference in any of the patient-reported outcome measures between conventional and navigated surgery. Interestingly, improved implant survivorship was observed in the navigated (0% revision rate) compared with the conventional group (4.9% all-cause revision rate). CONCLUSION: Electromagnetic computer navigated technology produces similar clinical outcomes compared with traditional surgery. Further work is required to monitor implant survivorship, and clinical outcomes with long-term follow-up, to determine the cost effectiveness of this technology.

Selective approach to preoperative echocardiography in esophageal atresia.

PURPOSE: Preoperative echocardiography is used routinely in neonates with esophageal atresia to identify patients in whom congenital cardiac disease will impact upon anesthetic and surgical decision-making. We aimed to determine the suitability of selective preoperative echocardiography. METHODS: We performed a single-center retrospective review of neonates with esophageal atresia over 6 years (2010-2015) at our tertiary pediatric institution. Data included preoperative clinical examination, chest x-ray, and echocardiography. Endpoints were cardiovascular, respiratory, radiological, and echocardiography findings. Selective strategies were assessed using sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: We identified 115 neonates with esophageal atresia. All underwent preoperative echocardiography. Cardiac defects were identified in 49/115 (43%) (major 9/115, moderate 4/115). Sensitivity, specificity, positive predictive value, and negative predictive value of abnormal clinical and radiologic assessment for major and moderate cardiac defects were 92%, 25%, 13%, 96%; for clinical examination alone were 92%, 25%, 14%, 96%; for absence of murmur, cyanosis, and abnormal respiratory examination were 92%, 28%, 13%, 97%. Selective strategies reduce echocardiograms performed by 22%. CONCLUSION: Selective strategies allow for identification of neonates with esophageal atresia who may have deferral of echocardiogram unill after surgery. Selection may improve timeliness of care and resource utilization, without compromising patient safety.

Significant differences in rates of aseptic loosening between two variations of a popular total knee arthroplasty design.

PURPOSE: The NexGen Legacy Posterior Stabilised (LPS) prosthesis (Zimmer Biomet, Warsaw, IN, USA) has augmentable and non-augmentable tibial baseplate options. We have noted an anecdotal increase in the number of cases requiring early revision for aseptic loosening since adopting the non-augmentable option. The purpose of this study was to ascertain our rates of aseptic tibial loosening for the two implant types within five years of implantation and to investigate the causes for any difference observed. METHODS: A database search was performed for all patients who underwent primary total knee arthroplasty (TKA) using the NexGen LPS between 2009 and 2015. Kaplan-Meier curves were plotted to assess for differences in revision rates between cohorts. We collected and compared data on gender, age, body mass index, component alignment and cement mantle quality as these were factors thought to affect the likelihood of aseptic loosening. RESULTS: Two thousand one hundred seventy-two TKAs were included with five year follow-up. There were 759 augmentable knees of which 14 were revised and 1413 non-augmentable knees of which 48 were revised. The overall revision rate at five years was 1.84% in the augmentable cohort and 3.4% in the non-augmentable cohort. The revision rate for aseptic loosening was 0.26% in the augmentable group and 1.42% in the non-augmentable group (p = 0.0241). CONCLUSIONS: We have identified increased rates of aseptic loosening in non-augmentable components. This highlights the effect that minor implant changes can have on outcomes. We recommend that clinicians remain alert to implant changes and publish their own results when important trends are observed.

Monoallelic BMP2 Variants Predicted to Result in Haploinsufficiency Cause Craniofacial, Skeletal, and Cardiac Features Overlapping Those of 20p12 Deletions.

Bone morphogenetic protein 2 (BMP2) in chromosomal region 20p12 belongs to a gene superfamily encoding TGF-ß-signaling proteins involved in bone and cartilage biology. Monoallelic deletions of 20p12 are variably associated with cleft palate, short stature, and developmental delay. Here, we report a cranioskeletal phenotype due to monoallelic truncating and frameshift BMP2 variants and deletions in 12 individuals from eight unrelated families that share features of short stature, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. De novo occurrence and autosomal-dominant inheritance of variants, including paternal mosaicism in two affected sisters who inherited a BMP2 splice-altering variant, were observed across all reported families. Additionally, we observed similarity to the human phenotype of short stature and skeletal anomalies in a heterozygous Bmp2-knockout mouse model, suggesting that haploinsufficiency of BMP2 could be the primary phenotypic determinant in individuals with predicted truncating variants and deletions encompassing BMP2. These findings demonstrate the important role of BMP2 in human craniofacial, skeletal, and cardiac development and confirm that individuals heterozygous for BMP2 truncating sequence variants or deletions display a consistent distinct phenotype characterized by short stature and skeletal and cardiac anomalies without neurological deficits.

Scanning Ion Conductance Microscopy Reveals Differences in the Ionic Environments of Gram-Positive and Negative Bacteria.

This paper reports on the use of scanning ion conductance microscopy (SICM) to locally map the ionic properties and charge environment of two live bacterial strains: the Gram-negative Escherichia coli and the Gram-positive Bacillus subtilis. SICM results find heterogeneities across the bacterial surface and significant differences among the Gram-positive and Gram-negative bacteria. The bioelectrical environment of the B. subtilis was found to be considerably more negatively charged compared to E. coli. SICM measurements, fitted to a simplified finite element method (FEM) model, revealed surface charge values of -80 to -140 mC m-2 for the Gram-negative E. coli. The Gram-positive B. subtilis show a much higher conductivity around the cell wall, and surface charge values between -350 and -450 mC m-2 were found using the same simplified model. SICM was also able to detect regions of high negative charge near B. subtilis, not detected in the topographical SICM response and attributed to the extracellular polymeric substance. To further explore how the B. subtilis cell wall structure can influence the SICM current response, a more comprehensive FEM model, accounting for the physical properties of the Gram-positive cell wall, was developed. The new model provides a more realistic description of the cell wall and allows investigation of the relation between its key properties and SICM currents, building foundations to further investigate and improve understanding of the Gram-positive cellular microenvironment.

Milrinone Acts as a Vasodilator But Not an Inotrope in Children After Cardiac Surgery-Insights From Wave Intensity Analysis.

OBJECTIVES: Milrinone is an inodilator widely used in the postoperative management of children undergoing cardiac surgery. The literature supporting its inotropic effect is sparse. We sought to study the effect of milrinone on the vasculature and its effects on the ventricular function using wave intensity analysis. We also intended to evaluate the feasibility of using wave intensity analysis by the bedside. DESIGN: prospective single-center observational study. SETTING: PICU of a tertiary children's hospital. PATIENTS: Children (< 18 yr) admitted to PICU following cardiac surgery who required to be commenced on a milrinone infusion. INTERVENTIONS: Echocardiography and Doppler ultrasound assessments for wave intensity analysis were performed prior to commencing milrinone and 4-6 hours after milrinone infusion. MEASUREMENTS AND MAIN RESULTS: Wave intensity analysis was successfully performed and analyzed in 15 of 16 patients (94%). We identified three waves-a forward compression wave, backward compression wave, and forward decompression wave. The waves were described with their cumulative intensity and wave-related pressure change. There was a 26% reduction in backward compression wave cumulative intensity following the introduction of milrinone. Other variables (backward compression wave cumulative intensity/forward compression wave cumulative intensity ratio, backward compression wave wave-related pressure change, backward compression wave wave-related pressure change/forward compression wave wave-related pressure change ratio) consistent with vasodilation also decreased after milrinone. It also decreased the vascular wavespeed by 7.1% and increased the distensibility of the vessels by 14.6%. However, it did not increase forward compression wave cumulative intensity, a variable indicating the systolic force generated by the ventricle. Forward decompression wave cumulative intensity indicating ventricular early diastolic relaxation also did not change. CONCLUSIONS: In a cohort of children recovering in PICU after having undergone cardiac surgery, we found that milrinone acted as a vasodilator but did not demonstrate an improvement in the contractility or an improved relaxation of the left ventricle as assessed by wave intensity analysis. We were able to demonstrate the feasibility and utility of wave intensity analysis to further understand ventriculo-vascular interactions in an intensive care setting.

Misconduct and Misbehavior Related to Authorship Disagreements in Collaborative Science.

Scientific authorship serves to identify and acknowledge individuals who "contribute significantly" to published research. However, specific authorship norms and practices often differ within and across disciplines, labs, and cultures. As a consequence, authorship disagreements are commonplace in team research. This study aims to better understand the prevalence of authorship disagreements, those factors that may lead to disagreements, as well as the extent and nature of resulting misbehavior. Methods include an international online survey of researchers who had published from 2011 to 2015 (8364 respondents). Of the 6673 who completed the main questions pertaining to authorship disagreement and misbehavior, nearly half (46.6%) reported disagreements regarding authorship naming; and discipline, rank, and gender had significant effects on disagreement rates. Paradoxically, researchers in multidisciplinary teams that typically reflect a range of norms and values, were less likely to have faced disagreements regarding authorship. Respondents reported having witnessed a wide range of misbehavior including: instances of hostility (24.6%), undermining of a colleague's work during meetings/talks (16.4%), cutting corners on research (8.3%), sabotaging a colleague's research (6.4%), or producing fraudulent work to be more competitive (3.3%). These findings suggest that authorship disputes may contribute to an unhealthy competitive dynamic that can undermine researchers' wellbeing, team cohesion, and scientific integrity.

Researchers' Perceptions of Ethical Authorship Distribution in Collaborative Research Teams.

Authorship is commonly used as the basis for the measurement of research productivity. It influences career progression and rewards, making it a valued commodity in a competitive scientific environment. To better understand authorship practices amongst collaborative teams, this study surveyed authors on collaborative journal articles published between 2011 and 2015. Of the 8364 respondents, 1408 responded to the final open-ended question, which solicited additional comments or remarks regarding the fair distribution of authorship in research teams. This paper presents the analysis of these comments, categorized into four main themes: (1) disagreements, (2) questionable behavior, (3) external influences regarding authorship, and (4) values promoted by researchers. Results suggest that some respondents find ways to effectively manage disagreements in a collegial fashion. Conversely, others explain how distribution of authorship can become a "blood sport" or a "horror story" which can negatively affect researchers' wellbeing, scientific productivity and integrity. Researchers fear authorship discussions and often try to avoid openly discussing the situation which can strain team interactions. Unethical conduct is more likely to result from deceit, favoritism, and questionable mentorship and may become more egregious when there is constant bullying and discrimination. Although values of collegiality, transparency and fairness were promoted by researchers, rank and need for success often overpowered ethical decision-making. This research provides new insight into contextual specificities related to fair authorship distribution that can be instrumental in developing applicable training tools to identify, prevent, and mitigate authorship disagreement.

Age and gender related differences in infection, thromboembolism, revision and death in knee arthroplasty in a Scottish population.

BACKGROUND AND AIMS: The aim of this large population based study was to investigate the effect of patient age and gender on the complication rates of knee arthroplasty surgery using data from the Scottish Arthroplasty Project joint registry. METHODS AND RESULTS: 55,636 knee arthroplasty procedures were included in the study and divided into four age categories (<55, 55-64, 65-75 and >75 years) for comparison of the 90-day deep vein thrombosis or pulmonary embolism (DVT/PE) and one-year infection rates and the mortality and revision rates up to ten-year follow up. The mean rate of DVT/PE was 1.4% with significantly higher rates in elderly patients (p = 0.0006). The mean one-year infection rate was 1.6% with a significantly increased rate of 1.9% in males (p = 0.0001). Mortality rates increased with age, the 10-year mortality in patients >75 years of age was 44.8%. Revision rates were increased in males and younger patients. CONCLUSION: Elderly patients showed higher rates of thromboembolic complications. There was no difference in infection rates between different age groups. The infection rate was higher in males. Younger patients need to be counselled about the increased risk of revision at 10 years.

A Cross-Sectional Study of the Prevalence of Exercise-Induced Hypertension in Childhood Following Repair of Coarctation of the Aorta.

BACKGROUND: Exercise-testing may be a more tolerable method of detecting hypertension in children after coarctation repair compared to gold-standard 24-hour ambulatory blood pressure (BP) monitoring (ABPM). This study aims to determine the prevalence of exercise-induced hypertension and end-organ damage in children after coarctation repair, and the effectiveness of exercise-testing compared to 24-hour ABPM in this population. METHODS: Exercise-testing (Bruce protocol), transthoracic echocardiogram, 24-hour ABPM, and pulse wave velocity were performed in 41 patients aged 8 to 18 years with previous coarctation repair. Median age at repair was 13 days. Exercise-testing data were compared to healthy paediatric controls. Hypertension was defined as BP >95th percentile on 24-hour ABPM compared to normalised data, and systolic BP (SBP) arbitrarily >200mmHg on exercise-testing. RESULTS: After 13±3years, 39% (14/36) were hypertensive on 24-hour ABPM and 12% (5/41) on exercise-testing. Coarctation patients had a higher peak exercise SBP and reduced endurance compared to controls (164±26mmHg vs. 148±19mmHg, p=0.003; and 13.0±1.7mins vs. 14.2±2.4mins, p=0.007; respectively). All patients with a peak exercise SBP >190mmHg were hypertensive on 24-hour ABPM. Pulse wave velocity was higher in hypertensive patients on exercise-testing and 24-hour ABPM compared to normotensive patients (p=0.004 and p=0.06; respectively). CONCLUSIONS: Exercise-testing may be a useful tool to detect hypertension in children and young adults after coarctation repair, particularly in those who do not tolerate 24-hour ABPM. Normative peak exercise BP data for age should be obtained to improve the accuracy of exercise-testing in detecting hypertension.

Big Data in Drug Discovery.

Interpretation of Big Data in the drug discovery community should enhance project timelines and reduce clinical attrition through improved early decision making. The issues we encounter start with the sheer volume of data and how we first ingest it before building an infrastructure to house it to make use of the data in an efficient and productive way. There are many problems associated with the data itself including general reproducibility, but often, it is the context surrounding an experiment that is critical to success. Help, in the form of artificial intelligence (AI), is required to understand and translate the context. On the back of natural language processing pipelines, AI is also used to prospectively generate new hypotheses by linking data together. We explain Big Data from the context of biology, chemistry and clinical trials, showcasing some of the impressive public domain sources and initiatives now available for interrogation.