Identification and Optimization of Novel Inhibitors of the Polyketide Synthase 13 Thioesterase Domain with Antitubercular Activity.

There is an urgent need for new tuberculosis (TB) treatments, with novel modes of action, to reduce the incidence/mortality of TB and to combat resistance to current treatments. Through both chemical and genetic methodologies, polyketide synthase 13 (Pks13) has been validated as essential for mycobacterial survival and as an attractive target for Mycobacterium tuberculosis growth inhibitors. A benzofuran series of inhibitors that targeted the Pks13 thioesterase domain, failed to progress to preclinical development due to concerns over cardiotoxicity. Herein, we report the identification of a novel oxadiazole series of Pks13 inhibitors, derived from a high-throughput screening hit and structure-guided optimization. This new series binds in the Pks13 thioesterase domain, with a distinct binding mode compared to the benzofuran series. Through iterative rounds of design, assisted by structural information, lead compounds were identified with improved antitubercular potencies (MIC < 1 µM) and in vitro ADMET profiles.

Residential mobility and mental health.

We examine the extent to which residential relocation within and between tenure types is associated with changes in mental health. We focus on four types of housing transition - rent-to-own, own-to-rent, own-to-own, and rent-to-rent - using Australian and UK panel data sets from 2001 to 2017. In both countries, transitions into homeownership and moves away from the mortgaged edges toward the unburdened mainstream of outright ownership are positively associated with mental health. On the other hand, shifts by mortgagors towards more precarious positions on the edges of ownership precipitate dips in mental health when there is exposure to high levels of payment and investment risks. Clearly, residential moves can both alleviate and introduce different kinds of risks that affect affordability. Moreover, tenure transitions have impacts on mental health beyond the impacts of payment and investment risks. However, we observe some cross-national differences in findings. In Australia, loss of homeownership has a negative impact on mental health that outweighs the mental health impacts of attaining ownership. In the UK, these findings are reversed. Acute housing affordability problems following moves in Australia, but not in the UK, are a significant driver of mental health outcomes. These differences have institutional explanations.

The Supercapsular Percutaneously Assisted Total Hip Approach Does Not Provide Any Clinical Advantage Over the Conventional Posterior Approach for THA in a Randomized Clinical Trial.

BACKGROUND: The supercapsular percutaneously assisted total hip (SuperPATH) approach was designed to be a less-invasive surgical approach to THA. This approach may have advantages, including less pain, more rapid mobilization, and shorter hospital length of stay. However, few published studies have compared the SuperPATH technique to existing standard approaches in a randomized, controlled manner. QUESTIONS/PURPOSES: In this study, we asked: (1) Do patients with SuperPATH demonstrate improved early function, using the timed up and go (TUG) and timed stair climbing (TSC) tests as instruments for assessment during the first 100 days postoperatively? (2) Are patient-reported outcomes, in the form of Oxford Hip Scores, better for the SuperPATH group during the first 3 months postoperatively? (3) Are opioid consumption and pain score in the first month postoperatively different between patients undergoing SuperPATH and patients undergoing a standard posterior approach? (4) Are patients with SuperPATH able to discontinue using mobility aids and return to work more quickly? METHODS: Between February 2017 and May 2019, 46% (46 of 101) of patients were recruited among 101 patients who met our inclusion criteria. Those 46 patients were randomized into two groups on the day of surgery; 54% (25 of 46) were assigned to the study group (SuperPATH approach) and 46% (21 of 46) were assigned to the control group (posterior approach). The SuperPATH technique uses the plane between the gluteus medius and the external rotators while preserving the piriformis and the superior aspect of the capsule. A percutaneous accessory portal is required for acetabular reaming and cup insertion. The posterior approach involves releasing short rotators and partially releasing the quadratus femoris while retaining the gluteus maximus's insertion site. The two groups did not differ in BMI, gender, American Society of Anesthesiologists class, surgical side, or diagnosis. The length of stay, component position, and blood loss were similar between the groups, but the operative time was longer in the SuperPATH group than in the group with the posterior approach. One patient from the control group was lost to follow-up and was excluded. Three patients in the study group had complications. The TUG and TSC tests are timed tasks for the patient. In the TUG test, patients stand from sitting, walk 3 meters and turn, walk back, and sit down. The TSC test measures the time taken to ascend and descend 10 steps. Patients were followed for 24 months for any complications. RESULTS: The TUG time at 100 days was 8.9 ± 2.6 seconds in the SuperPATH group and 8.7 ± 2.2 seconds in the posterior group (mean difference -0.2 seconds [95% CI -1.8 to 1.4]; p = 0.98); results were similar at other timepoints. The TSC time at 100 days was 11.6 ± 4.7 seconds in the SuperPATH group and 10.8 ± 3.6 seconds in the posterior group (mean difference -0.7 seconds [95% CI -3.5 to 2.1]; p = 0.88), and there were no differences between the two groups at all timepoints. The Oxford Hip Score showed no difference at any point postoperatively. At 6 weeks, it was 36 ± 5.9 points in the SuperPATH group and 38 ± 8.6 in the posterior group (mean difference 1.7 points [95% CI -2.7 to 6.1]; p = 0.51). At 3 months, it was 42± 6.7 points in the SuperPATH group and 41 ± 10.2 points in the posterior group (mean difference 0.7 points [95% CI -6.2 to 4.9]; p = 0.34). Patients' pain scores did not show any differences at all tested timepoints (mean difference 1 [95% CI -0.2 to 2.2]; p = 0.102). Total opioid consumption in the posterior group was higher in the first 2 weeks than that in the SuperPATH group (mean difference 6 [95% CI 2.3 to 9.9]; p = 0.001), but there was no difference in either group by week 4 (mean difference 0.4 [95% CI -0.5 to 1.4]; p = 0.36). There was no difference in return to work between the SuperPATH group and the posterior approach group (mean difference 6 days [95% CI -29 to 41]; p = 0.74). Discontinuation of mobility aids was similar between the two groups (mean difference 0.9 days [95% CI -25 to 27]; p = 0.94). CONCLUSION: The SuperPATH approach had no clinical advantages over the posterior approach, resulted in more complications, and only showed a short-term reduction in pain. The results of our small randomized controlled trial can be used to calculate future sample sizes, but our data suggest that any differences favoring the SuperPATH approach are likely to be small and transient. This approach should not be used routinely in clinical practice until an adequately powered trial shows clinically important differences in patient-relevant endpoints. The improved postoperative recovery is likely multifactorial and not dependent on the invasiveness of the approach. LEVEL OF EVIDENCE: Level II, therapeutic study.

Effect of Osteochondroplasty on Time to Reoperation After Arthroscopic Management of Femoroacetabular Impingement: Analysis of a Randomized Controlled Trial.

Background: A subset of patients with femoroacetabular impingement (FAI) fail arthroscopic management. It is not clear which patients will fail surgical management; however, several surgical and patient factors, such as type of procedure and age, are thought to be important predictors. Purpose: This time-to-event analysis with a 27-month follow-up analysis compared the effect of (1) arthroscopic osteochondroplasty with or without labral repair versus (2) arthroscopic lavage with or without labral repair on the time to reoperation in adults aged 18 to 50 years with FAI. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Eligible participants had been randomized in a previous study trial to a treatment of arthroscopic osteochondroplasty or arthroscopic lavage with or without labral repair. Using the comprehensive data set from the Multinational Femoroacetabular Impingement Randomized controlled Trial, all reoperations until 27 months after surgery were identified. The analysis was conducted using a Cox proportional hazards model, with percentage of patients with a reoperation evaluated in a time-to-event analysis as the outcome. The independent variable was the procedure, with age and impingement subtype explored as potential covariates. The effects from the Cox model were expressed as the hazard ratio (HR). All tests were 2-sided, with an alpha level of .05. Results: A total of 108 patients in the osteochondroplasty group and 106 patients in the lavage group were included. The mean age of the patients included in the study was 36 ± 8.5 years. Overall, 27 incident reoperations were identified within the 27-month follow-up, with an incidence rate of 6 per 100 person-years. Within the osteochondroplasty group, 8 incident reoperations were identified (incidence rate, 3.4 per 100 person-years), while within the lavage group, 19 incident reoperations were identified (incidence rate, 8.7 per 100 person-years). The hazard of reoperation for patients undergoing osteochondroplasty was 40% of that of patients undergoing lavage (HR, 0.40 [95% CI, 0.17-0.91] P = .029). Conclusion: This study demonstrated that for adults between the ages of 18 and 50 years with FAI, arthroscopic osteochondroplasty was associated with a 2.5-fold decrease in the hazard of reoperation at any point in time compared with arthroscopic lavage. Registration: NCT01623843 (ClinicalTrials.gov identifier).

The Spatial Dynamics of Homelessness in Australia: Urbanisation, Intra-City Dynamics and Affordable Housing.

While homelessness in Australia has remained relatively stable at the national level, its spatial distribution is becoming more nuanced. This paper draws on homelessness estimates produced by the Australian Bureau of Statistics to explore the spatial dynamics of homelessness in Australia over a fifteen-year period. Building on existing work, we show that homelessness is becoming more urbanised with evidence of spatial convergence, mainly driven by a surge in severe crowding in our major cities. However, when exploring intra-city patterns, we find distinctive intra-city spatial dynamics featuring strong suburbanisation of 'couch surfing' in state capital cities, contrasting with shifts in severe crowding numbers toward middle and inner regions of most state capitals. We argue that these dynamics reflect the retreat of affordable rental housing supply to the outer suburban fringe, and the coping strategies that 'couch surfers' and those aspiring to live in the inner cities are compelled to follow in response to the changing spatial configuration of affordable housing.

The Psychological Impact of COVID-19 on Arthroplasty Surgeons.

BACKGROUND: After the COVID-19 pandemic declaration in March 2020, all the elective total joint replacement surgeries in Canada were abruptly canceled for an indefinite period of time. The principal objective of this study was to determine the prevalence of psychological morbidity experienced by arthroplasty surgeons during the peak of the first wave of the COVID-19 pandemic. Secondary objectives included characterizing influential variables affecting the surgeon's well-being and suggesting directives for improvement. METHODS: This study surveyed Canadian Arthroplasty Society (CAS) members regarding their psychological well-being using the validated General Health Questionnaire (GHQ-12), the Center for Epidemiological Studies Depression (CES-D) scale, and the Personal Wellbeing Index-Adult (PWI-A). As well, the survey included questions regarding concerns about COVID-19, precautionary measures, personal well-being, and sociodemographic characteristics. RESULTS: A total of 80 surgeons (52% of those surveyed) completed the questionnaire, representing all 10 provinces in Canada. The prevalence of emotional distress and depression were 38% and 29%, respectively. Psychological morbidity most commonly resulted from concerns of loss of income/operating time, experiences of emotional conflict, and generalized safety worries. The surgeons commonly (93%) demonstrated insight in recognizing the impact of COVID-19 on their emotional health. CONCLUSION: Canadian arthroplasty surgeons demonstrated emotional resilience and insight during COVID-19. Continual communication, as well as remuneration action plans, could improve the mental well-being of at-risk individuals.

Meeting AT needs in humanitarian crises: The current state of provision.

Humanitarian coordination systems increasingly recognize and aim to respond to the needs of people with disabilities within populations affected by crises, spurred on by the UN Convention on the Rights of Persons with Disabilities (CRPD) which was adopted in 2006. Many agencies state their aim to meet the requirements of the CRPD using a "twin track" approach: ensuring the inclusion of people with disabilities in mainstream provision, alongside targeted support for their needs, which may include the need for Assistive Technology (AT). However, there is very little evidence of AT provision in humanitarian settings, which is a specific and urgent need for many people including the elderly and people with disabilities, and an implicit requirement of Article 11 of the CRPD and World Health Assembly resolution on improving access to assistive technology. There is also little evidence of effective mechanisms for AT provision in humanitarian settings. This is despite high and growing levels of unmet AT need in crises, and despite the legally binding requirement in the CRPD to provide AT for those who need it. AT provision faces unique challenges in humanitarian settings. This paper discusses the evidence available in the literature for the scale and quality of AT provision interventions in crises, and what is known about the challenges and facilitators of provision. We conducted a search of the academic literature and retained literature that reported on any form of AT provision following crisis, where international humanitarian response was in place, published in English between January 2010 and June 2020. We found very few examples in that academic literature of systematic and coordinated AT provision at the acute stage of crisis, and even less in the preparedness and post-acute stages. However, it is difficult to assess whether this is the result of insufficient academic attention or reflects a lack of provision. The small body of academic literature that describes AT provision in humanitarian settings paints a picture of small-scale provision, specialized to single types of impairments, and delivered by predominantly by NGOs. We also conducted a search of the gray literature, using the same inclusion criteria, in two countries: Afghanistan and South Sudan (case studies forthcoming). This gray literature provided supplementary evidence of the types of AT providers and AT provision available in those protracted crises. There are very few examples of how AT services can be scaled up (from a very low baseline) and maintained sustainably within a strengthened health system. The literature also describes more examples of provision of assistive products for mobility over assistive products for other impairments. If the paucity of literature on AT provision in humanitarian settings is a reflection of the scale of provision, this implies a deficiency in humanitarian response when it comes to providing people with AT needs with the essential products and services to which they have a right, and which will enable their access to basic, life-saving assistance. We conclude by providing recommendations for urgent actions that the AT and humanitarian community must take to fill this critical gap in the provision of essential products and services for a potentially marginalized and excluded group.

Management of Mycobacterium tuberculosis Prosthetic Joint Infection: 2 Cases and Literature Review.

Prosthetic joint infection caused by Mycobacterium tuberculosis (TBPJI) is uncommon but can be encountered in immunocompromised patients or those from tuberculosis-endemic regions. A lack of clinical suspicion and experience with TBPJI often leads to a delay in diagnosis. We report 2 cases of TBPJI in a Hungarian-Canadian and Iranian-Canadian immigrant, respectively. Both were treated with concurrent surgical and medical therapy. We also performed a literature review on TBPJI case reports, outlining their diagnosis and management.

Adductor canal block with or without added magnesium sulfate following total knee arthroplasty: a multi-arm randomized controlled trial.

PURPOSE: Postoperative analgesia following total knee arthroplasty (TKA) often includes intrathecal opioids, periarticular injection (PAI) of local anesthetic, systemic multimodal analgesia, and/or peripheral nerve blockade. The adductor canal block (ACB) provides analgesia without muscle weakness and magnesium sulphate (MgSO4) may extend its duration. The purpose of this trial was to compare the duration and quality of early post-TKA analgesia in patients receiving postoperative ACB (± MgSO4) in addition to standard care. METHODS: Elective TKA patients were randomized to: 1) sham ACB, 2) ropivacaine ACB, or 3) ropivacaine ACB with added MgSO4. All received spinal anesthesia with intrathecal morphine, intraoperative PAI, and multimodal systemic analgesia. Patients and assessors remained blinded to allocation. Anesthesiologists knew whether patients had received sham or ACB but were blinded to MgSO4. The primary outcome was time to first analgesic (via patient-controlled analgesia [PCA] with iv morphine) following ACB. Secondary outcomes were morphine consumption, side effects, visual analogue scale pain scores, satisfaction until 24 hr postoperatively, and length of stay. RESULTS: Of 130 patients, 121 were included. Nine were excluded post randomization: four were protocol violations, three did not meet inclusion criteria, and two had severe pain requiring open label blockade. There were no differences in the median [interquartile range] time to first PCA request: sham, 310 min [165-550]; ropivacaine ACB, 298 min [120-776]; and ropivacaine ACB with MgSO4, 270 min [113-780] (P = 0.96). Similarly, we detected no differences in resting pain, opioid consumption, length of stay, or associated side effects until 24 hr postoperatively. CONCLUSION: We found no analgesic benefit of a postoperative ACB, with or without added MgSO4, in TKA patients undergoing spinal anesthesia and receiving intrathecal morphine, an intraoperative PAI, and multimodal systemic analgesia. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02581683); registered 21 October 2015.

RéSUMé: OBJECTIF: L'analgésie postopératoire suivant une arthroplastie totale du genou (ATG) inclut souvent des opioïdes intrathécaux, une injection périarticulaire (IPA) d'anesthésique local, une analgésie multimodale systémique, et/ou des blocs des nerfs périphériques. Le bloc du canal des adducteurs (BCA) permet une analgésie sans faiblesse musculaire et le sulfate de magnésium (MgSO4) pourrait prolonger sa durée. L'objectif de cette étude était de comparer la durée et la qualité de l'analgésie post-ATG précoce chez les patients recevant un BCA postopératoire (± MgSO4) en plus des soins standard. MéTHODE: Des patients devant subir une ATG non urgente ont été randomisés à recevoir : 1) un BCA placebo (groupe témoin), 2) un BCA avec ropivacaïne, ou 3) un BCA avec ropivacaïne et MgSO4. Tous ont reçu une rachianesthésie avec morphine intrathécale, une IPA peropératoire, et une analgésie multimodale systémique. L'allocation a été faite à l'insu des patients et des évaluateurs. Les anesthésiologistes savaient si les patients avaient reçu un placebo ou un BCA, mais n'étaient pas informés de l'ajout ou non de MgSO4. Le critère d'évaluation principal était le temps jusqu'à la première prise d'analgésique (via une analgésie contrôlée par le patient [ACP] avec de la morphine iv) après le BCA. Les critères secondaires comprenaient la consommation de morphine, les effets secondaires, les scores de douleur sur l'échelle visuelle analogue, la satisfaction jusqu'à 24 heures postopératoires, et la durée de séjour. RéSULTATS: Sur 130 patients, 121 ont été inclus. Neuf ont été exclus après la randomisation : quatre l'ont été en raison de violations du protocole, trois ne répondaient pas aux critères d'inclusion, et deux ont ressenti des douleurs graves nécessitant un bloc sans insu. Aucune différence n'a été observée dans le temps médian [écart interquartile] jusqu'à la première demande d'ACP : placebo, 310 min [165-550]; BCA ropivacaïne, 298 min [120-776]; et BCA ropivacaïne avec MgSO4, 270 min [113-780] (P = 0,96). De la même manière, nous n'avons détecté aucune différence dans la douleur au repos, la consommation d'opioïdes, la durée de séjour, ou les effets secondaires associés jusqu'à 24 heures postopératoires. CONCLUSION: Nous n'avons trouvé aucun avantage analgésique à un BCA postopératoire, avec ou sans ajout de MgSO4, chez les patients subissant une ATG sous rachianesthésie et recevant de la morphine intrathécale, une IPA peropératoire, et une analgésie multimodale systémique. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02581683); enregistrée le 21 octobre 2015.

Osteochondroplasty and Labral Repair for the Treatment of Young Adults With Femoroacetabular Impingement: A Randomized Controlled Trial.

BACKGROUND: Femoroacetabular impingement (FAI) is a condition known to cause hip pain in young adults. PURPOSE: To evaluate the efficacy of the surgical correction of FAI via arthroscopic osteochondroplasty with or without labral repair compared with arthroscopic lavage of the hip joint with or without labral repair. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 220 male and female participants aged 18 to 50 years with nonarthritic FAI suitable for surgical treatment were recruited for the trial at 10 clinical centers in Canada, Finland, and Denmark between October 2012 and November 2017, of whom 214 were included in the final analysis. In the osteochondroplasty group, cam- and/or pincer-type lesions were resected using fluoroscopic guidance. In the lavage group, the joint was washed out with 3 L of normal saline. Surgeons were instructed to repair the labrum in both groups if it was mechanically unstable once probed, showing visible displacement or chondrolabral separation. The primary outcome was patient-reported pain (using the 100-point visual analog scale [VAS]) at 12 months. Secondary outcomes included hip function (Hip Outcome Score [HOS] and International Hip Outcome Tool), physical and mental health (12-Item Short Form Health Survey), and health utility (EuroQol-5 Dimensions) at 12 months as well as any reoperations and other hip-related adverse events at 24 months. RESULTS: At 12 months, there was no difference in pain (VAS) between the groups (mean difference [MD], 0.11 [95% CI, -7.22 to 7.45]; P = .98). Also, 88.3% (189/214) of participants had a labral tear, of which 60.3% were repaired. For the secondary outcomes, there were no significant differences between treatment groups, with the exception of the HOS activities of daily living domain in which lavage showed significant improvement compared with osteochondroplasty (MD, -5.03 [95% CI, -10.40 to -0.03]; P = .049). By 24 months, there were significantly fewer reoperations reported in the osteochondroplasty group (8/105) than the lavage group (19/104) (odds ratio, 0.37 [95% CI, 0.15-0.89]; P = .026). The primary reasons for a reoperation included hip pain (15/27; 55.6%) and a reinjury of the labrum (11/27; 40.7%). CONCLUSION: Both the osteochondroplasty and the lavage groups with or without labral repair for FAI had significantly improved pain or function significantly at 1 year. By 2 years, the reoperation rate was significantly lower in the osteochondroplasty group. REGISTRATION: NCT01623843 (ClinicalTrials.gov identifier).

Effects of accelerated versus standard care surgery on the risk of acute kidney injury in patients with a hip fracture: a substudy protocol of the hip fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) international randomised controlled trial.

INTRODUCTION: Inflammation, dehydration, hypotension and bleeding may all contribute to the development of acute kidney injury (AKI). Accelerated surgery after a hip fracture can decrease the exposure time to such contributors and may reduce the risk of AKI. METHODS AND ANALYSIS: Hip fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) is a multicentre, international, parallel-group randomised controlled trial (RCT). Patients who suffer a hip fracture are randomly allocated to either accelerated medical assessment and surgical repair with a goal of surgery within 6 hours of diagnosis or standard care where a repair typically occurs 24 to 48 hours after diagnosis. The primary outcome of this substudy is the development of AKI within 7 days of randomisation. We anticipate at least 1998 patients will participate in this substudy. ETHICS AND DISSEMINATION: We obtained ethics approval for additional serum creatinine recordings in consecutive patients enrolled at 70 participating centres. All patients provide consent before randomisation. We anticipate reporting substudy results by 2021. TRIAL REGISTRATION NUMBER: NCT02027896; Pre-results.

Rationale and design of the HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) Trial: a protocol for an international randomised controlled trial evaluating early surgery for hip fracture patients.

INTRODUCTION: Annually, millions of adults suffer hip fractures. The mortality rate post a hip fracture is 7%-10% at 30 days and 10%-20% at 90 days. Observational data suggest that early surgery can improve these outcomes in hip fracture patients. We designed a clinical trial-HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) to determine the effect of accelerated surgery compared with standard care on the 90-day risk of all-cause mortality and major perioperative complications. METHODS AND ANALYSIS: HIP ATTACK is a multicentre, international, parallel group randomised controlled trial (RCT) that will include patients ≥45 years of age and diagnosed with a hip fracture from a low-energy mechanism requiring surgery. Patients are randomised to accelerated medical assessment and surgical repair (goal within 6 h) or standard care. The co-primary outcomes are (1) all-cause mortality and (2) a composite of major perioperative complications (ie, mortality and non-fatal myocardial infarction, pulmonary embolism, pneumonia, sepsis, stroke, and life-threatening and major bleeding) at 90 days after randomisation. All patients will be followed up for a period of 1 year. We will enrol 3000 patients. ETHICS AND DISSEMINATION: All centres had ethics approval before randomising patients. Written informed consent is required for all patients before randomisation. HIP ATTACK is the first large international trial designed to examine whether accelerated surgery can improve outcomes in patients with a hip fracture. The dissemination plan includes publishing the results in a policy-influencing journal, conference presentations, engagement of influential medical organisations, and providing public awareness through multimedia resources. TRIAL REGISTRATION NUMBER: NCT02027896; Pre-results.

Short stay total joint arthroplasty program: patient factors predicting readmission

Background: The aim of this study was to evaluate the effectiveness of our short stay arthroplasty program as measured by 30-day readmission rate and the rate of transfer to inpatient care. Risk factors for readmission/transfer were also evaluated and contrasted with current patient screening criteria. Methods: We retrospectively reviewed 297 charts for all primary total joint arthroplasties completed in the short stay program during an 18-month period. Data included readmission and patient characteristics such as age, sex, comorbidities, the American Society of Anesthesiologists (ASA) physical classification grade, body mass index (BMI) and the number of preoperative medications. Results: The 30-day readmission rate was 2.6% (n = 8). With the inclusion of patients transferred to the inpatient hospital, the overall failure rate of our short stay program was 6.7% (n = 20). Multivariable modelling controlling for age, BMI and ASA suggested that those with an in-hospital complication were 11.4 times more likely to be readmitted or transferred to inpatient care (p < 0.001) with a trend for patients who were taking more medications (p = 0.09). Conclusion: The current readmission rate from this program is comparable to previously published data in the arthroplasty literature. However, several patients required transfer to inpatient care, which significantly impacted the effectiveness of the short stay program. Risk factors for readmission/transfer are not completely accounted for by current presurgical screening criteria. Further evaluation of the Blaylock Risk Assessment Screening Score is required to determine its value for predicting hospital readmission.

Contexte: Cette étude avait pour but d'évaluer l'efficacité de notre programme d'arthroplastie court séjour sur la base du taux de réadmission à 30 jours et du taux de conversion en hospitalisation. Les facteurs de risque de réadmission/conversion ont aussi été évalués et mis en parallèle avec les critères actuels de sélection des patients. Méthodes: Nous avons passé en revue de manière rétrospective les 297 dossiers d'arthroplasties totales primaires effectuées dans le cadre du programme court séjour sur une période de 18 mois. Les données incluaient les réadmissions et les caractéristiques des patients telles que âge, sexe, comorbidités, score ASA (classification de l'état de santé physique selon l'American Society of Anesthesiologists), indice de masse corporelle (IMC) et nombre de médicaments courants. Résultats: Le taux de réadmission à 30 jours a été de 2,6 % (n = 8). En incluant les cas de conversion en hospitalisation, le taux d'échec global de notre programme court séjour a été de 6,7 % (n = 20). Après ajustement selon un modèle multivarié tenant compte de l'âge, de l'IMC et de la classification de l'ASA, les patients ayant présenté une complication justifiant l'hospitalisation étaient 11,4 fois plus susceptibles d'être réadmis ou hospitalisés (p < 0,001), avec une tendance proportionnelle au nombre de médicaments courants avant l'intervention (p = 0,09). Conclusion: Le taux actuel de réadmission pour ce programme est comparable aux données publiées antérieurement dans la littérature sur l'arthroplastie. Toutefois, plusieurs patients ont eu besoin d'être hospitalisés, ce qui a eu un impact significatif sur l'efficacité du programme court séjour. Les facteurs de risque de réadmission/conversion ne sont pas entièrement expliqués par les critères de sélection préchirurgicaux actuels. Il faudra continuer d'évaluer le score Blaylock d'estimation des risques pour en déterminer l'utilité à prédire les réhospitalisations.

Discovery of Soft-Drug Topical Tool Modulators of Sphingosine-1-phosphate Receptor 1 (S1PR1).

In order to study the role of S1PRs in inflammatory skin disease, S1PR modulators are dosed orally and topically in animal models of disease. The topical application of S1PR modulators in these models may, however, lead to systemic drug concentrations, which can complicate interpretation of the observed effects. We set out to design soft drug S1PR modulators as topical tool compounds to overcome this limitation. A fast follower approach starting from the drug ponesimod allowed the rapid development of an active phenolic series of soft drugs. The phenols were, however, chemically unstable. Protecting the phenol as an ester removed the instability and provided a compound that is converted by enzymatic hydrolysis in the skin to the phenolic soft drug species. In simple formulations, topical dosing of these S1PR modulators to mice led to micromolar skin concentrations but no detectable blood concentrations. These topical tools will allow researchers to investigate the role of S1PR in skin, without involvement of systemic S1PR biology.

All-Polyethylene Tibial Components in Total Knee Replacement: Early Failures.

In total primary knee replacement surgery, the use of all-polyethylene tibial (APT) components has many advantages, including no backside wear and no linear dissociation. In addition, the greater polyethylene thickness permits more conservative bone resection compared with that for metal-backed components, with a lower unit cost and similar functional results. Thus, the use of an APT in primary total knee arthroplasty remains an attractive option. This is a review of 158 patients who underwent primary knee replacement using APT components from a single manufacturer. Data collection included age, American Society of Anesthesiology physical status classification, body mass index (BMI), type of deformity, the presence of diabetes mellitus, rate of revision, and characteristics associated with early failure of the components. Average follow-up time was 40 months. The revision rate for any reason was 5.6%, and the average BMI in revision cases was 37.6. Patients with a higher BMI (≥ 37.6) were significantly more likely to require revision surgery than patients with a lower BMI (p = 0.04). In our sample, high BMI was a contributing factor for early failures in total knee replacements using an APT component. Generally, polyethylene tibial components used for primary knee replacements are safe and effective, with good outcomes and subsequent lower costs to the health care system.

Outcomes of hip and knee total joint arthroplasty in a Canadian inmate population over a 10-year period

Background: Little information exists regarding the risk of complications in inmates who receive total hip or knee arthroplasties in Canada. Inmates tend to be less healthy owing to socioeconomic factors and an increased number of medical and psychiatric comorbidities. We compared revision and complication rates of total joint replacements in a cohort of incarcerated Canadians versus a cohort of non-inmates. Methods: We obtained a list of all Canadian inmate inpatient hospital visits with diagnostic/procedure codes of primary hip or knee arthroplasty within the last 10 years from our institution's discharge abstract database. Demographic data and information related to the perioperative course, along with any data related to postoperative complications/readmissions, were obtained through manual chart review. Results: The inmate group consisted of 20 men (mean age 58 yr) with a total of 24 primary total joint arthroplasties; the comparison group included 171 men (mean age 62 yr). Postoperatively, the inmates had a 4-fold increased risk of major complication compared with non-inmates (33.3% v. 7.6%; odds ratio 4.21, p = 0.01). The inmates' revision rate was 20.8% compared with 5.8% in the comparison group (p = 0.03). The most common cause for revision in the inmate group was infection, with a rate of 16.7% compared with 3.5% in the comparison group (p = 0.03). Conclusion: Patients requiring total joint arthroplasty who are inmates in the Canadian penitentiary system are at increased risk of complication and revision surgeries following total joint arthroplasty.

Contexte: Il y a peu de données concernant le risque de complications chez les détenus opérés pour une prothèse totale de la hanche ou du genou au Canada. Les détenus tendent à être en moins bonne santé en raison de divers facteurs socioéconomiques et d'un nombre accru de comorbidités médicales et psychiatriques. Nous avons comparé les taux de révision et de complications suite à des arthroplasties articulaires totales dans une cohorte de Canadiens incarcérés comparée à une cohorte d'individus non incarcérés. Méthodes: Nous avons extrait de la base de données sur les congés des patients de notre établissement la liste de toutes les consultations de détenus hospitalisés assorties aux codes de diagnostics et d'interventions concernant les arthroplasties de la hanche ou du genou au cours des 10 dernières années. Les données démographiques et les renseignements relatifs à la période périopératoire, de même que les données concernant les complications postopératoires ou réadmissions ont été obtenus au moyen d'un examen manuel des dossiers. Résultats: Le groupe de détenus se composait de 20 hommes (âgés en moyenne de 58 ans) totalisant 24 arthroplasties articulaires totales primaires; le groupe de comparaison incluait 171 hommes (âgés en moyenne de 62 ans). En période postopératoire, les détenus étaient exposés à un risque 4 fois plus élevé de complications majeures, comparativement aux individus non incarcérés (33,3 % c. 7,6 %; risque relatif 4,21, p = 0,01). Le taux de révision chez les détenus a été de 20,8 %, contre 8 % dans le groupe de comparaison (p = 0,03). La plus fréquente cause de révision chez les détenus était l'infection, avec un taux de 16,7 %, contre 3,5 % dans le groupe de comparaison (p = 0,03).

Can the Blaylock Risk Assessment Screening Score (BRASS) predict length of hospital stay and need for comprehensive discharge planning for patients following hip and knee replacement surgery? Predicting arthroplasty planning and stay using the BRASS.

BACKGROUND: Knee and hip arthroplasty constitutes a large percentage of hospital elective surgical procedures. The Blaylock Risk Assessment Screening Score (BRASS) was designed to identify patients in need of discharge planning. The purpose of this study was to evaluate whether the BRASS was associated with length of stay (LOS) in hospital following elective arthroplasty. METHODS: We retrospectively reviewed the charts of individuals undergoing primary elective arthroplasty for knee or hip osteoarthritis who had a documented BRASS score. RESULTS: In our study cohort of 241, both BRASS (p < 0.001) and replacement type (hip v. knee; p = 0.048) were predictive of LOS. Higher BRASS was associated with older patients (p < 0.001), higher American Society of Anesthesiologists score (p < 0.001) and longer LOS (p < 0.001). We found a specificity of 83% for a BRASS greater than 8 and a hospital stay longer than 5 days and a specificity of 92% for a BRASS greater than 10. CONCLUSION: The BRASS represents a novel and significant predictor of LOS following elective arthroplasty. Patients with higher BRASS are more likely to stay in hospital 5 days or more and should receive pre-emptive social work consultations to facilitate timely discharge planning and hospital resources.

CONTEXTE: Les arthroplasties du genou et de la hanche représentent un fort pourcentage des interventions chirurgicales non urgentes pratiquées dans les hôpitaux. Le score BRASS (Blaylock Risk Assessment Screening Score) a été conçu pour reconnaître les patients dont il faut planifier le congé de l'hôpital. Le but de la présente étude était de vérifier s'il y a un lien entre le score BRASS et la durée du séjour hospitalier (DSH) après une arthroplastie non urgente. MÉTHODES: Nous avons analysé rétrospectivement les dossiers de patients soumis à une arthroplastie primaire non urgente du genou ou de la hanche dont le score BRASS avait été documenté. RÉSULTATS: Dans la cohorte de 241 patients de notre étude, le score BRASS (p < 0,001) et le type d'arthroplastie (hanche c. genou, p = 0,048) ont été des facteurs prédicteurs de la DSH. Un score BRASS plus élevé était associé à un âge plus avancé des patients (p < 0,001), à un score plus élevé à l'échelle de l'American Society of Anesthesiologists (p < 0,001) et à une DSH plus longue (p < 0,001). Nous avons observé une spécificité de 83 % pour un score BRASS supérieur à 8 et un séjour hospitalier de plus de 5 jours, et une spécificité de 92 % pour un score BRASS supérieur à 10. CONCLUSION: Le score BRASS constitue un nouveau prédicteur important de la DSH après une arthroplastie non urgente. Les patients dont le score BRASS est plus élevé, risquent davantage de séjourner plus de 5 jours à l'hôpital et devraient bénéficier de consultations préventives auprès du personnel des Services sociaux afin de faciliter la planification des congés en temps opportun et d'assurer l'utilisation efficace des ressources hospitalières.

Recognition of minor adult hip dysplasia: which anatomical indices are important?

The rise in popularity of hip arthroscopy has led to a renewed interest in mild hip dysplasia. There is a lack of clarity in the literature regarding both the diagnosis and management of such patients. The aim of this study was to analyse the relative importance of and the inter-relationship between the classically described anatomical indices of dysplasia.One hundred and fifty hips with varying degrees of hip dysplasia were studied. The following were measured: centre-edge (CE), Sharp's and Tönnis angles, acetabular head index (AHI), and acetabular index of depth to width (AIDW). Spearman's correlation coefficient was calculated.Using the CE angle 82 hips were classified as normal and 68 dysplastic. Of the 82 patients with a normal CE angle, 20-39% were dysplastic on at least one other variable. The CE angle did not have a significant correlation to other variables. The remaining four variables showed inter-correlations between 0.26 and 0.54. Overall the Tönnis angle showed the strongest correlation with the other variables. In the patient group with CE angles 21o to 25o (minor dysplasia) 72% of hips had Tönnis angles greater than 10o and 28% had angles greater than or equal to 15o indicating the great variability in the level of dysplasia within this group.In patients with mild dysplasia we have shown that measurement of a single anatomical variable may lead to under-diagnosis. We recommend the measurement the CE angle combined with at least one other variable and suggest the use of the Tönnis angle.