Rapid induction of transdermal buprenorphine to subcutaneous extended-release buprenorphine for the treatment of opioid use disorder.

BACKGROUND: Buprenorphine is an effective and safe treatment for opioid use disorder, but the requirement for moderate opioid withdrawal symptoms to emerge prior to initiation is a significant treatment barrier. CASE PRESENTATION: We report on two cases of hospitalized patients with severe, active opioid use disorder, in which we initiated treatment with transdermal buprenorphine over 48 h, followed by the administration of a single dose of sublingual buprenorphine/naloxone and then extended-release subcutaneous buprenorphine. The patients did not experience precipitated withdrawal and only had mild withdrawal symptoms. CONCLUSIONS: This provides preliminary evidence for a rapid induction strategy that may improve tolerability, caregiver burden, and treatment retention as compared to previous induction strategies.

Systematic review on intentional non-medical fentanyl use among people who use drugs.

Objectives: Fentanyl is a highly potent opioid and has, until recently, been considered an unwanted contaminant in the street drug supply among people who use drugs (PWUD). However, it has become a drug of choice for an increasing number of individuals. This systematic review evaluated intentional non-medical fentanyl use among PWUD, specifically by summarizing demographic variance, reasons for use, and resulting patterns of use. Methods: The search strategy was developed with a combination of free text keywords and MeSH and non-MeSH keywords, and adapted with database-specific filters to Ovid MEDLINE, Embase, Web of Science, and PsychINFO. Studies included were human studies with intentional use of non-medical fentanyl or analogues in individuals older than 13. Only peer-reviewed original articles available in English were included. Results: The search resulted in 4437 studies after de-duplication, of which 132 were selected for full-text review. Out of 41 papers included, it was found that individuals who use fentanyl intentionally were more likely to be young, male, and White. They were also more likely to have experienced overdoses, and report injection drug use. There is evidence that fentanyl seeking behaviours are motivated by greater potency, delay of withdrawal, lower cost, and greater availability. Conclusions: Among PWUD, individuals who intentionally use fentanyl have severe substance use patterns, precarious living situations, and extensive overdose history. In response to the increasing number of individuals who use fentanyl, alternative treatment approaches need to be developed for more effective management of withdrawal and opioid use disorder. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021272111.

48-hour Induction of Transdermal Buprenorphine to Extended-release Buprenorphine.

ABSTRACT: Buprenorphine extended-release (BUP-XR) provides sustained delivery of buprenorphine to control withdrawal and craving symptoms in the form of a monthly injectable and has been shown to improve health outcomes in patients with opioid use disorder. It is recommended that patients are stabilized with a transmucosal buprenorphine product, for at least 7 days per the product monograph; however, clinically, this timeline may be expedited. We report a case of a hospitalized patient with unregulated fentanyl use who underwent a successful transdermal buprenorphine induction for 48 hours to initiate BUP-XR with minimal levels of withdrawal and without precipitating opioid withdrawal. The approach described could provide a practical, patient-centered, accelerated induction strategy that, once independently validated, could considerably facilitate the use of BUP-XR.

Design and experimental validation of the oxazole and thiazole derivatives as potential antivirals against of human cytomegalovirus.

QSAR studies of a set of previously synthesized azole derivatives tested against human cytomegalovirus (HCMV) were performed using the OCHEM web platform. The predictive ability of the classification models has a balanced accuracy (BA) of 73-79%. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds with a reasonable accuracy within the applicability domain (BA = 76-83%). The models were applied to screen a virtual chemical library with expected activity of compounds against HCMV. The five most promising new compounds were identified, synthesized and their antiviral activities against HCMV were evaluated in vitro. Two of them showed some activity against the HCMV strain AD169. According to the results of docking analysis, the most promising biotarget associated with HCMV is DNA polymerase. The docking of the most active compounds 1 and 5 in the DNA polymerase active site shows calculated binding energies of -8.6 and -7.8 kcal/mol, respectively. The ligand's complexation was stabilized by the formation of hydrogen bonds and hydrophobic interactions with amino acids Lys60, Leu43, Ile49, Pro77, Asp134, Ile135, Val136, Thr62 and Arg137.

Targeting p21-activated kinase 1 for development of a novel anti-arrhythmic drug class.

Evidence accumulated over the past decade suggests that p21-activated kinase 1 (PAK1) is a critical cardiac-protective signalling molecule. The present article provides an updated review of recent findings regarding the role of PAK1 in maintaining normal cardiac electrophysiological function through its regulation of membrane and Ca2+ clocks. We first overviewed the PAK1 activation mechanism. We then discussed recent updated results showing the action mechanisms of PAK1 signalling on Cav1.2/Cav1.3 (ICaL)-mediated Ca2+ entry, ryanodine receptor type 2-mediated sarcoplasmic reticulum (SR) Ca2+ release, transcriptional regulation of SR Ca2+-ATPase 2a, Na+/Ca2+ exchangers, and Ca2+/calmodulin-dependent protein kinase II. Finally, we proposed a new and exciting route for developing a PAK1-based therapeutic strategy for cardiac arrhythmias. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Impact of human coronavirus infections on paediatric patients at a tertiary paediatric hospital: a retrospective study of the prepandemic era.

BACKGROUND: Human coronaviruses (HCoVs) are important respiratory pathogens in humans and animals. Most HCoVs are emerging pathogens, with five known human pathogens identified in the last two decades. AIM: To examine the clinical course of HCoV infection in children to improve understanding of severity and outcomes. METHODS: A retrospective review was undertaken of all encounters of children with known HCoV infection at a tertiary paediatric hospital from January 2015 to January 2018. Electronic medical records were reviewed for demographic data, HCoV type, viral co-pathogens, time to testing, need for hospitalization, requirement for higher-level care (HLC) including intensive care unit management and requirement for oxygen support, radiographic findings suggestive of lower respiratory tract (LRT) disease, and length of stay (LOS). FINDINGS: In total, 450 encounters for 430 different patients were identified, with the majority (85%) being inpatient. OC43 was the most common HCoV. Younger patients (age <5 years) had higher probability of hospitalization [adjusted odds ratio (aOR) 2.2, 95% confidence interval (CI) 1.2-4.1], requirement for HLC (aOR 1.8, 95% CI 1.0-3.1) and presence of LRT findings on chest radiographs (aOR 1.7, 95% CI 1.01-2.9). Clinical outcomes did not differ between HCoV types, except LOS which was longer for 229E. Fifty-two (11%) encounters were detected after 3 days of hospitalization (median 25.5 days), suggesting possible nosocomial infection. CONCLUSION: HCoVs are important respiratory pathogens in the paediatric population, especially among patients aged <5 years who are at increased risk for severe disease. The role of HCoVs as hospital-acquired pathogens may be underappreciated.

Opium tincture versus methadone for opioid agonist treatment: a randomized controlled trial.

AIM: To test if opium tincture (OT) was non-inferior to methadone in retaining participants in opioid agonist treatment (OAT). DESIGN: A Phase III, multi-centre, parallel-group, non-inferiority, double-blind randomized controlled trial with an allocation ratio of 1:1. Participants were provided treatment and followed for a period of 85 days. SETTING: Four OAT clinics in Iran. PARTICIPANTS: Two hundred and four participants with opioid use disorder [mean age (standard deviation) = 37.4 (9.3); female 11.3%] recruited between July 2017 and January 2018. INTERVENTIONS: Participants were assigned to either OT (102) or methadone (102) using a patient-centred flexible dosing strategy. MEASUREMENTS: Treatment retention over 85 days was the primary outcome. Self-reported opioid use outside treatment and occurrence of adverse events (AEs) were the secondary outcomes. FINDINGS: Remaining in treatment at the end of the follow-up were 68.6% in the methadone arm and 59.8% in the OT arm. The relative retention rate of methadone to OT was 1.15 (0.97, 1.36) in both intent-to-treat and per-protocol analyses; non-inferiority was not supported statistically, as the upper bound of the confidence interval exceeded our pre-specified non-inferiority margin (1.25). Opioid use outside treatment was reported by 30.3% of OT (n = 152) and 49.4% of methadone (n = 168) patients, a difference in proportions of -19%: 90% confidence interval (-28%, -10%). The total count of AEs in the OT arm (22 among nine individuals) was significantly higher (P = 0.04) than that in the methadone arm (three among two individuals). Nausea was the most common side effect. CONCLUSION: While this study could not conclude the non-inferiority of opium tincture (OT) to methadone for retaining patients in opioid agonist treatment, OT retained 60% of participants to end of follow-up (85 days) and was superior to methadone in reducing self-reported opioid use outside treatment.

Blood loss and transfusion risk in intramedullary nailing for subtrochanteric fractures.

BACKGROUND: The incidence of hip fractures and subtrochanteric fractures in particular is increasing, along with the globally expanding aging population. Intramedullary nailing remains the 'gold standard' of their treatment. Blood loss can be a result of the original trauma, but also secondary to the subsequent surgical insult, especially during the reaming of the intramedullary canal. OBJECTIVES: The aim of our study was to report on the blood loss and incidence of blood transfusion in patients presenting with a subtrochanteric fracture treated with intramedullary nailing. Most importantly, we aim to identify factors associated with the need for transfusion within the first 48 h post-operatively. METHODS: Following institutional board approval, 431 consecutive patients (131 males; age: 79.03 years old, SD 13.68 years) presenting in a Level 1 Trauma Centre with a subtrochanteric fracture treated with an intramedullary nail were retrospectively identified, over an 8-year period. Exclusion criteria included patients with high energy injuries, pathological fractures, primary operations at other institutions and patients lost to follow-up. To identify risk factors leading to increased risk of transfusion, we first compared patients requiring intra-operative transfusion or transfusion during the first 48 h post-operatively against those who did not require transfusion. This was then followed by multivariate regression analysis adjusted for confounding factors to identify the most important risk factors associated with need for transfusion within the first 48 h post-operatively. RESULTS: Incidence of blood transfusion was 6.0% pre-operatively, compared to 62.7% post-operatively. A total of 230 patients (52.3%) required either intra-operative transfusion or transfusion during the first 48 h following surgery. Patients having a transfusion within the first 48 h post-operatively had a higher incidence of escalation in their care (p = 0.050), LOS (p = 0.015), 30-day (p = 0.033) and one-year mortality (p = 0.004). Multivariate regression analysis adjusted for confounding factors identified that the most important association of a need for transfusion within the first 48 post-operative hours was a pre-operative Hb <100 g/L (OR 6.64); a nail/canal ratio <70% (OR 3.92), followed by need for open reduction (OR 2.66). Fracture involving the lesser trochanter was also implicated with an increased risk (OR 2.08). Additionally, pre-operative moderate/severe renal impairment (OR 4.56), as well as hypoalbuminaemia on admission (OR 2.10) were biochemical predictors of an increased risk of transfusion. Most importantly, the need for transfusion was associated with an increase in 30-day mortality (OR 12.07). CONCLUSION: Several patient, fracture and surgery related factors are implicated with an increased risk for transfusion within the first 48-h post-operatively. Early identification, and where possible correction of these factors can potentially reduce blood loss and risk of transfusion, along with all the associated sequelae and mortality risk. LEVEL OF EVIDENCE: III.

48-hour Induction of Transdermal Buprenorphine to Sublingual Buprenorphine/Naloxone: The IPPAS Method.

Buprenorphine is an effective medication for the treatment of opioid use disorder. However, the traditional method of buprenorphine induction requires a period of abstinence and the development of at least moderate withdrawal, which can be barriers in starting treatment. We present the case of a hospitalized patient with opioid use disorder using unregulated fentanyl, who underwent a transdermal buprenorphine induction over 48 hours to initiate sublingual buprenorphine/naloxone on the third day. The patient experienced minimal levels of withdrawal and did not experience precipitated withdrawal. The ease of use of this novel induction method over previously published induction protocols can greatly improve the accessibility of buprenorphine for patients and healthcare staff.

Developing A Rapid Transfer from Opioid Full Agonist to Buprenorphine: "Ultrarapid Micro-Dosing" Proof of Concept.

Buprenorphine/naloxone has been shown to be effective for treating opioid use disorder (OUD). However, the traditional method of induction requires a patient to be in moderate-to-severe withdrawal, which is challenging, time-consuming, and a common reason for leaving against medical advice. Induction strategies that minimize the severity and duration of patient discomfort while enabling patients to reach therapeutic doses during short hospital admissions can mitigate difficulties when inducing a patient on buprenorphine/naloxone. This case-series illustrates two patients with OUD using illicit fentanyl, who were successfully started on buprenorphine/naloxone using 24-hour and 6-hour micro-dosing induction protocol. During induction, the patients were up-titrated to a therapeutic dose through ultrarapid micro-dosing with ongoing use of short-acting opioids. Both patients reached therapeutic doses experiencing minimal levels of withdrawal. This case-series is a proof of concept for the use of a buprenorphine/naloxone ultrarapid micro-induction protocol for inpatients with OUD. By reducing the length of induction and precluding the need for withdrawal, this method offers several advantages over previously published inductions protocols and can improve the accessibility of buprenorphine/naloxone to patients with OUD.

Lower limb post-traumatic osteomyelitis: a systematic review of clinical outcomes.

PURPOSE: The aim of this study was to examine the patient-reported outcomes of patients presenting with post-traumatic osteomyelitis (PTOM) of the lower limb over the past 15 years. This period was chosen to reflect modern treatment principles and increased centralisation of care. METHODS: An electronic literature search of the relevant databases (PubMed, Ovid Medline, Embase, and the Cochrane library) was conducted to identify studies published between January 2006 and July 2021 reporting series of greater than 10 patients with PTOM of the tibia or femur at the site of a previous fracture. Studies reporting septic non-union were excluded. RESULTS: Sixteen eligible studies were identified and included in the final report. Remission of infection was achieved in 93.2% of cases (range 70-100%), whilst amputation was reported in 1-7% of cases. A variety of patient-reported outcome measures were utilised including the lower extremity functional scale, short musculoskeletal functional assessment, Enneking score, and EQ-5D-3L. Limb-specific functional outcomes returned to levels similar to that of the general population although poorer outcomes were noted in specific cohorts including those with complex anatomic disease and active medical comorbidities. CONCLUSION: Infection following fracture fixation remains a difficult problem to treat. Regardless, using modern treatments and techniques patients can have comparable functional outcomes to that of the general population. High-quality studies are required to advance our knowledge into which types of treatments offer a benefit and how to further improve outcomes.

Operative management of acetabular fractures in the elderly: a case series.

BACKGROUND: Our objective was to identify acetabular fractures in the elderly population (over 60 years of age), treated with open reduction and internal fixation (ORIF), and to examine their outcomes, primarily the risk for need for further surgery in the form of a total hip arthroplasty (THA), and factors associated with it. Additional outcomes such as infection, avascular necrosis (AVN) of the femoral head, and heterotopic ossification (HO) were also investigated. METHODS: Following institutional review board (IRB) approval, a retrospective analysis of all consecutive patients presenting to a Level I Trauma Centre over a 13-years period (January 2003-February 2016) was conducted. Patients were excluded if their initial treatment was conservative or simultaneous ORIF with THA. RESULTS: A total of 62 patients with an age of 71.5 ± 8.04 years were included (14 female; follow-up 54.2 months, range 1-195 months). Sixteen patients required a THA as a secondary procedure due to symptomatic post-traumatic arthritis (25.8%), five (8.1%) of whom having a THA within a year from the original trauma (three patients presenting with loss of reduction and two patients with early AVN). No associations with progression to THA were identified. Surgical approach (ilioinguinal) was the only factor associated with increased risk of development of HO (p = 0.010). The median post-operative survival following an acetabular fracture treated with ORIF was calculated at 90.1 months (95% CI 72.9-107.2). CONCLUSION: Acetabular fractures ORIF in the elderly, is a safe and reliable option. The relatively incidence of development of severe post-operative arthritis was 45.2%. Conversion to THA was 25.8%, with 8.1% having the arthroplasty procedure within a year of the original trauma surgery. LEVEL OF EVIDENCE: III.

Cost Analysis of Buprenorphine Extended-Release Injection Versus Sublingual Buprenorphine/Naloxone Tablets in a Correctional Setting.

Incarcerated clients experience high rates of opioid use disorder and overdose. It is critical that opioid agonist treatment (OAT) is provided in correctional facilities. However, few receive OAT due to concerns about diversion, misuse, and safety. Buprenorphine extended-release (BUP-XR), a monthly buprenorphine depot injection, could be especially advantageous in the correctional setting as it can prevent diversion and misuse, saving staff resources and time. An injection of BUP-XR is costly compared with a monthly supply of buprenorphine/naloxone (BUP/NX) tablets. We demonstrate that when factoring in the added costs of medication preparation, administration, monitoring, and personnel, it is more economical to provide BUP-XR than BUP/NX. Other facilities, by utilizing our cost breakdown, can determine whether BUP-XR is economically advantageous at their own facility.

Subtrochanteric femoral fractures and intramedullary nailing complications: a comparison of two implants.

INTRODUCTION: Intramedullary (IM) nails are considered the 'gold' standard treatment for subtrochanteric femoral fractures. The incidence and risk factors for re-operation in subtrochanteric fractures remain unclear. Furthermore, no studies have compared the outcomes of different nailing systems used to treat subtrochanteric fractures in the same study population. AIMS/OBJECTIVES: Our study aimed to (i) investigate the cumulative incidence and factors associated with an increased risk of re-operation in subtrochanteric fractures treated with a long intramedullary (IM) nail, (ii) compare the outcomes of subtrochanteric fractures treated with long Affixus and Gamma nails, and (iii) establish whether the addition of a proximal anti-rotation screw in the Affixus nail confers any clinical benefit. METHODS: A retrospective review of all adult patients admitted to a level 1 trauma centre with a subtrochanteric femur fracture treated with a long cephalomedullary IM nail over an 8-year period was conducted. Exclusion criteria were primary surgery performed at another institution, prophylactic nailing because of tumours, incomplete fractures, and patients who were lost to follow-up or died before fracture healing. Data variables were assessed for normality prior to determining the use of either parametric or non-parametric tests. Logistic regression analysis was performed to identify potential factors associated with re-operation. For the comparison between the two nail types, patients were matched into two groups of 119 each by age (10-year intervals), gender and mechanism of injury (low energy, high energy and pathological fractures). A p-value < 0.05 was considered significant. The Kaplan-Meier nail survival curve was used to demonstrate the survival of each nail. Data were analysed using the statistical package R (R version 3.6.0). RESULTS: A total of 309 subtrochanteric fractures were treated with a distally locked long IM nail (re-operation rate: 22.33%) over an 8-year period. Logistic regression identified six factors associated with an increased risk of re-operation, including age < 75 years old, use of a long Gamma nail, pre-injury coxa-vara femoral neck shaft angles, an immediate post-operative reduction angle of > 10° varus, deep wound infection and non-union. Following matching, we compared the two long cephalomedullary nailing systems used (Gamma versus Affixus nail). The only differences identified from the unadjusted analysis were a higher overall incidence of nail failure in Gamma nails due to any cause, re-operation, and impingement of the nail tip distally against the anterior femoral cortex. When we corrected for covariates, no significant differences remained evident between the two nails. From the Kaplan-Meier nail survival curves, however, the Affixus nail demonstrated better survivorship up to 5 years post-implantation in terms of nail failure and re-operation for all causes. Finally, the addition of a proximal anti-rotation screw in the Affixus nail did not seem to confer any benefit. CONCLUSION: We reported a 22.3% re-operation rate in our cohort of subtrochanteric fractures treated with a long IM nail. We have identified six risk factors associated with re-operation: age < 75 years old, pre-injury femoral neck shaft angle, choice of nail, varus reduction angle, fracture-related infection and non-union. The addition of a proximal anti-rotation screw in the Affixus nail did not confer any benefit.

Case report: acute care management of severe opioid withdrawal with IV fentanyl.

BACKGROUND: An increasing number of individuals who use drugs in North America are preferentially consuming fentanyl over other opioids. This has significant consequences on the treatment and management of opioid use disorder (OUD) and its concurrent disorders, especially in acute care if opioid requirements are not met. CASE PRESENTATION: We present a patient with severe OUD and daily injection of fentanyl, admitted to hospital for management of acute physical health issues. Due to high opioid requirements and history of patient-initiated discharge, intravenous fentanyl was administered for treatment of opioid withdrawal, and management of pain, which supported continued hospitalization for acute care treatment and aligned with substance use treatment goals. CONCLUSION: This case demonstrates that intravenous fentanyl for management of OUD in hospital can be a feasible approach to meet opioid requirements and avoid fentanyl withdrawal among patients with severe OUD and daily fentanyl use, thereby promoting adherence to medical treatment and reducing the risk of patient-initiated discharge. There is an urgent need to tailor current treatment strategies for individuals who primarily use fentanyl. Carefully designed research is needed to further explore the use of IV fentanyl for acute care management of severe opioid withdrawal in a hospital setting.

Biological and molecular profile of fracture non-union tissue: A systematic review and an update on current insights.

Fracture non-union represents a common complication, seen in 5%-10% of all acute fractures. Despite the enhancement in scientific understanding and treatment methods, rates of fracture non-union remain largely unchanged over the years. This systematic review investigates the biological, molecular and genetic profiles of both (i) non-union tissue and (ii) non-union-related tissues, and the genetic predisposition to fracture non-union. This is crucially important as it could facilitate earlier identification and targeted treatment of high-risk patients, along with improving our understanding on pathophysiology of fracture non-union. Since this is an update on our previous systematic review, we searched the literature indexed in PubMed Medline; Ovid Medline; Embase; Scopus; Google Scholar; and the Cochrane Library using Medical Subject Heading (MeSH) or Title/Abstract words (non-union(s), non-union(s), human, tissue, bone morphogenic protein(s) (BMPs) and MSCs) from August 2014 (date of our previous publication) to 2 October 2021 for non-union tissue studies, whereas no date restrictions imposed on non-union-related tissue studies. Inclusion criteria of this systematic review are human studies investigating the characteristics and properties of non-union tissue and non-union-related tissues, available in full-text English language. Limitations of this systematic review are exclusion of animal studies, the heterogeneity in the definition of non-union and timing of tissue harvest seen in the included studies, and the search term MSC which may result in the exclusion of studies using historical terms such as 'osteoprogenitors' and 'skeletal stem cells'. A total of 24 studies (non-union tissue: n = 10; non-union-related tissues: n = 14) met the inclusion criteria. Soft tissue interposition, bony sclerosis of fracture ends and complete obliteration of medullary canal are commonest macroscopic appearances of non-unions. Non-union tissue colour and surrounding fluid are two important characteristics that could be used clinically to distinguish between septic and aseptic non-unions. Atrophic non-unions had a predominance of endochondral bone formation and lower cellular density, when compared against hypertrophic non-unions. Vascular tissues were present in both atrophic and hypertrophic non-unions, with no difference in vessel density between the two. Studies have found non-union tissue to contain biologically active MSCs with potential for osteoblastic, chondrogenic and adipogenic differentiation. Proliferative capacity of non-union tissue MSCs was comparable to that of bone marrow MSCs. Rates of cell senescence of non-union tissue remain inconclusive and require further investigation. There was a lower BMP expression in non-union site and absent in the extracellular matrix, with no difference observed between atrophic and hypertrophic non-unions. The reduced BMP-7 gene expression and elevated levels of its inhibitors (Chordin, Noggin and Gremlin) could potentially explain impaired bone healing observed in non-union MSCs. Expression of Dkk-1 in osteogenic medium was higher in non-union MSCs. Numerous genetic polymorphisms associated with fracture non-union have been identified, with some involving the BMP and MMP pathways. Further research is required on determining the sensitivity and specificity of molecular and genetic profiling of relevant tissues as a potential screening biomarker for fracture non-unions.

Treatment approaches and outcome trajectories for youth with high-risk opioid use: A narrative review.

AIM: First use of opioids often happens in adolescence and an increasing number of opioid overdoses are being reported among youth. The purpose of this narrative review was to present the treatment approaches for youth with high-risk opioid use, determine whether the literature supports the use of opioid agonist treatment among youth and identify evidence for better treatment outcomes in the younger population. METHODS: A search of the literature on PubMed using MeSH terms specific to youth, opioid use and treatment approaches generated 1436 references. Following a screening process, 137 papers were found to be relevant to the treatment of high-risk opioid use among youth. After full-text review, 19 eligible studies were included: four randomized controlled trials, nine observational studies and six reviews. RESULTS: Research for the different treatment options among youth is limited. The available evidence shows better outcomes in terms of retention in care and cost-effectiveness for opioid agonist treatment than abstinence-based comparisons. Integrating psychosocial interventions into the continuum of care for youth can be an effective way of addressing comorbid psychiatric conditions and emotional drivers of substance use, leading to improved treatment trajectories. CONCLUSIONS: From the limited findings, there is no evidence to deny youth with high-risk opioid use the same treatment options available to adults. A combination of pharmacological and youth-specific psychosocial interventions is required to maximize retention and survival. There is an urgent need for more research to inform clinical strategies toward appropriate treatment goals for such vulnerable individuals.

Development and Validation of a Post-Operative Non-Union Risk Score for Subtrochanteric Femur Fractures.

BACKGROUND: Our objective was to develop and validate a predictive model for non-union following a subtrochanteric fracture of the femur. METHODS: Following institutional board approval, 316 consecutive patients presenting to our institution (84 non-unions) who fulfilled the inclusion criteria were retrospectively identified. To identify potential unadjusted associations with progression to non-union, simple logistic regression models were used, followed by a revised adjusted model of multiple logistic regression. RESULTS: Having established the risk factors for non-union, the coefficients were used to produce a risk score for predicting non-union. To identify the high-risk patients in the early post-operative period, self-dynamisation was excluded. The revised scoring system was the sum of the following: diabetes (6); deep wound infection (35); simple or severe comminution (13); presence of an atypical fracture (14); lateral cortex gap size ≥5 mm (11), varus malreduction (5-10 degrees) (9); varus malreduction (>10 degrees) (20). On the ROC (receiver operating characteristic) curve, the area under the curve (0.790) demonstrated very good discriminatory capability of the scoring system, with good calibration (Hosmer-Lemeshow test; p = 0.291). Moreover, 5-fold cross validation confirmed good fit of the model and internal validity (accuracy 0.806; Kappa 0.416). The cut-point determined by Youden's formula was calculated as 18. CONCLUSION: This study demonstrates that the risk of non-union can be reliably estimated in patients presenting with a subtrochanteric fracture, from the immediate post-operative period. The resulting non-union risk score can be used not only to identify the high-risk patients early, offering them appropriate consultation and in some cases surgical intervention, but also informs surgeons of the modifiable surgery related factors that contribute to this risk.

Shifting North American drug markets and challenges for the system of care.

Drug markets are dynamic systems which change based on demand, competition, legislation and revenue. Shifts that are not met with immediate and appropriate responses from the healthcare system can lead to public health crises with tragic levels of morbidity and mortality, as experienced Europe in the early 1990s and as is the case in North America currently. The major feature of the current drug market shift in North America is towards highly potent synthetic opioids such as fentanyl and fentanyl analogues. An additional spike in stimulant use further complicates this issue. Without understanding the ever-changing dynamics of drug markets and consequent patterns of drug use, the healthcare system will continue to be ineffective in its response, and morbidity and mortality will continue to increase. Economic perspectives are largely neglected in research and clinical contexts, but better treatment alternatives need to consider the large-scale macroeconomic conditions of drug markets as well as the behavioural economics of individual substance use. It is important for policy makers, health authorities, first responders and medical providers to be aware of the clinical implications of drug market changes in order to best serve people who use drugs. Only with significant clinical research, a comprehensive reorganization of the system of care across all sectors, and an evidence-driven governance, will we be successful in addressing the challenges brought on by the recent shifts in drug markets.

Simultaneous induced membrane technique to reconstruct an obliterated floating knee.

The induced membrane technique, first described by Masquelet, is a powerful surgical approach that can be used to address segmental bone loss of various aetiologies. Despite ongoing debate regarding optimal delivery, the indications and limits of its application have been tested in increasingly complex situations, highlighting its considerable potential. We present a case of a devastating open lower limb injury with simultaneous femoral and ipsilateral tibial bone loss including articular injury on both sides of the joint. The Masquelet technique was used to successfully address both segments of bone loss within the same limb.