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1.
Haemophilia ; 30(1): 180-194, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38082543

ABSTRACT

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.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Hemophilia A , Humans , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Hip/adverse effects , Hemophilia A/complications , Retrospective Studies , Knee Joint , Risk Factors
2.
AIDS Res Ther ; 21(1): 17, 2024 03 21.
Article in English | MEDLINE | ID: mdl-38515183

ABSTRACT

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).


Subject(s)
Anti-HIV Agents , HIV Infections , HIV Seropositivity , HIV-1 , Oxazines , Piperazines , Pyridones , Humans , Male , Female , Lamivudine/adverse effects , Anti-HIV Agents/adverse effects , HIV Infections/drug therapy , Heterocyclic Compounds, 3-Ring/adverse effects , Anti-Retroviral Agents/therapeutic use , HIV Seropositivity/drug therapy , RNA
3.
Heart Lung Circ ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38755045

ABSTRACT

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.

4.
Knee Surg Sports Traumatol Arthrosc ; 31(3): 751-759, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36166095

ABSTRACT

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.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Surgery, Computer-Assisted , Humans , Arthroplasty, Replacement, Knee/methods , Prospective Studies , Treatment Outcome , Knee Joint/surgery , Surgery, Computer-Assisted/methods , Osteoarthritis, Knee/surgery
5.
J Acad Ethics ; 21(2): 269-292, 2023.
Article in English | MEDLINE | ID: mdl-35975128

ABSTRACT

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.

6.
Br J Neurosurg ; 36(2): 241-250, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34382881

ABSTRACT

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.


Subject(s)
Essential Tremor , Essential Tremor/surgery , Follow-Up Studies , Humans , Quality of Life , Thalamus/diagnostic imaging , Thalamus/surgery , Treatment Outcome , Tremor/surgery
7.
Clin Anat ; 35(8): 1107-1113, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35668648

ABSTRACT

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.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Arthroplasty, Replacement, Knee/methods , Cadaver , Female , Humans , Knee Joint/surgery , Male , Rotation , Tibia/surgery
8.
Eur J Orthop Surg Traumatol ; 32(6): 1127-1136, 2022 Aug.
Article in English | MEDLINE | ID: mdl-34357474

ABSTRACT

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.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Aluminum Oxide , Arthroplasty, Replacement, Hip/adverse effects , Ceramics , Follow-Up Studies , Humans , Middle Aged , Prosthesis Design , Prosthesis Failure , Reoperation , Treatment Outcome
9.
J Arthroplasty ; 36(10): 3451-3455, 2021 10.
Article in English | MEDLINE | ID: mdl-34226082

ABSTRACT

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.


Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Osteoarthritis, Knee , Surgery, Computer-Assisted , Electromagnetic Phenomena , Follow-Up Studies , Humans , Knee Joint/surgery , Osteoarthritis, Knee/surgery , Prospective Studies , Prosthesis Failure , Single-Blind Method , Treatment Outcome
10.
Pediatr Surg Int ; 37(4): 503-509, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33388963

ABSTRACT

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.


Subject(s)
Echocardiography , Esophageal Atresia/diagnostic imaging , Heart Defects, Congenital/diagnostic imaging , Preoperative Care/methods , Female , Humans , Infant, Newborn , Male , Retrospective Studies , Tracheoesophageal Fistula/surgery
11.
Int Orthop ; 45(11): 2859-2867, 2021 11.
Article in English | MEDLINE | ID: mdl-34392378

ABSTRACT

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.


Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Arthroplasty, Replacement, Knee/adverse effects , Humans , Knee Joint/surgery , Knee Prosthesis/adverse effects , Prosthesis Design , Prosthesis Failure , Reoperation , Retrospective Studies
12.
Am J Hum Genet ; 101(6): 985-994, 2017 Dec 07.
Article in English | MEDLINE | ID: mdl-29198724

ABSTRACT

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.


Subject(s)
Bone Morphogenetic Protein 2/genetics , Craniofacial Abnormalities/genetics , Developmental Disabilities/genetics , Dwarfism/genetics , Haploinsufficiency/genetics , Heart Defects, Congenital/genetics , Animals , Bone and Bones/embryology , Child , Child, Preschool , Chromosomes, Human, Pair 20/genetics , Cleft Palate/genetics , Disease Models, Animal , Female , Heart/embryology , Humans , Infant , Male , Mice , Mice, Knockout , Transforming Growth Factor beta/genetics
13.
Anal Chem ; 92(24): 16024-16032, 2020 12 15.
Article in English | MEDLINE | ID: mdl-33241929

ABSTRACT

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.


Subject(s)
Bacillus/cytology , Escherichia coli/cytology , Finite Element Analysis , Microscopy , Bacillus/metabolism , Cell Wall/metabolism , Cellular Microenvironment , Escherichia coli/metabolism
14.
Crit Care Med ; 48(11): e1071-e1078, 2020 11.
Article in English | MEDLINE | ID: mdl-32932352

ABSTRACT

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.


Subject(s)
Cardiac Surgical Procedures/methods , Cardiotonic Agents/therapeutic use , Milrinone/therapeutic use , Vasodilator Agents/therapeutic use , Cardiac Surgical Procedures/adverse effects , Cardiotonic Agents/administration & dosage , Echocardiography , Female , Heart Defects, Congenital/surgery , Heart Ventricles/diagnostic imaging , Humans , Infant , Infusions, Intravenous , Male , Milrinone/administration & dosage , Prospective Studies , Vasodilator Agents/administration & dosage , Ventricular Function/drug effects
15.
Sci Eng Ethics ; 26(4): 1967-1993, 2020 08.
Article in English | MEDLINE | ID: mdl-31161378

ABSTRACT

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.


Subject(s)
Authorship , Biomedical Research , Dissent and Disputes , Scientific Misconduct , Female , Humans , Male , Research Personnel
16.
Sci Eng Ethics ; 26(4): 1995-2022, 2020 08.
Article in English | MEDLINE | ID: mdl-31165383

ABSTRACT

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.


Subject(s)
Authorship , Biomedical Research , Research Personnel , Female , Humans , Male , Morals , Perception , Publications
17.
Scott Med J ; 65(3): 89-93, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32594896

ABSTRACT

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.


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/statistics & numerical data , Surgical Wound Infection/epidemiology , Thromboembolism/epidemiology , Age Distribution , Aged , Aged, 80 and over , Arthroplasty, Replacement, Knee/mortality , Female , Humans , Male , Middle Aged , Scotland/epidemiology , Sex Distribution , Thromboembolism/complications
18.
Heart Lung Circ ; 28(5): 792-799, 2019 May.
Article in English | MEDLINE | ID: mdl-29691159

ABSTRACT

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.


Subject(s)
Aortic Coarctation/surgery , Blood Pressure/physiology , Exercise Test/adverse effects , Exercise/physiology , Hypertension/epidemiology , Adolescent , Aortic Coarctation/physiopathology , Blood Pressure Monitoring, Ambulatory , Child , Cross-Sectional Studies , Echocardiography , Female , Follow-Up Studies , Humans , Hypertension/etiology , Hypertension/physiopathology , Male , Postoperative Period , Prevalence , Pulse Wave Analysis , Retrospective Studies , Time Factors , Victoria/epidemiology
19.
Prog Med Chem ; 57(1): 277-356, 2018.
Article in English | MEDLINE | ID: mdl-29680150

ABSTRACT

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.


Subject(s)
Big Data , Computational Biology , Drug Discovery , Artificial Intelligence , Drug Design , Humans
20.
Cardiol Young ; 28(11): 1299-1305, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30149816

ABSTRACT

BACKGROUND: Exercise training has been shown to increase exercise capacity in survivors of Fontan surgery. The geographic distribution of the Fontan population has been a barrier to hospital-based exercise training programmes. The objective of this study was to establish whether a home exercise training programme could achieve similar improvements to a hospital programme. METHODS: Adolescents with a Fontan circulation aged 12-19 years were prospectively recruited in a hospital or home exercise training programme. Patients underwent cardiopulmonary exercise testing and completed the Paediatric Quality of Life Inventory at initial assessment and after completion of an 8-week programme. Both groups performed two 1-hour training sessions per week. Patients in the home training programme had their first session in the hospital, and then progressed independently with one phone consult per week and one home visit by a physiotherapist. RESULTS: In total, 17 patients, with a mean age of 15±3 years, completed the training programme (six hospital). Characteristics and baseline performance of patients were similar in both groups. Oxygen consumption at anaerobic threshold increased from 19.3±3.8 to 21.6±6.0 ml/kg/minute (p=0.02) and peak oxygen pulse increased from 8.8±2.5 to 9.5±2.7 ml/beat (p=0.049). Total quality of life scale improved from 68 to 74% (p=0.01) and psychosocial health improved from 67 to 74% (p=0.02). No patient experienced training-related complications. CONCLUSIONS: Exercise training is beneficial and most likely safe after Fontan, resulting in improved exercise capacity and self-reported quality of life. Home exercise training programmes are probably as effective as hospital programmes. Home exercise training programmes should be integrated in the follow-up care of patients undergoing Fontan surgery.


Subject(s)
Exercise Therapy/methods , Fontan Procedure , Heart Defects, Congenital/surgery , Home Care Services , Inpatients , Postoperative Care/methods , Quality of Life , Adolescent , Child , Exercise Tolerance/physiology , Female , Heart Defects, Congenital/physiopathology , Heart Defects, Congenital/rehabilitation , Humans , Male , Surveys and Questionnaires , Treatment Outcome , Young Adult
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