Nanomolecularly-induced Effects at Titania/Organo-Diphosphonate Interfaces for Stable Hybrid Multilayers with Emergent Properties.

Nanoscale hybrid inorganic-organic multilayers are attractive for accessing emergent phenomena and properties through superposition of nanomolecularly-induced interface effects for diverse applications. Here, we demonstrate the effects of interfacial molecular nanolayers (MNLs) of organo-diphosphonates on the growth and stability of titania nanolayers during the synthesis of titania/MNL multilayers by sequential atomic layer deposition and single-cycle molecular layer deposition. Interfacial organo-diphosphonate MNLs result in ∼20-40% slower growth of amorphous titania nanolayers and inhibit anatase nanocrystal formation from them when compared to amorphous titania grown without MNLs. Both these effects are more pronounced in multilayers with aliphatic backbone-MNLs and likely related to impurity incorporation and incomplete reduction of the titania precursor indicated by our spectroscopic analyses. In contrast, both MNLs result in two-fold higher titania nanolayer roughness, suggesting that roughening is primarily due to MNL bonding chemistry. Such MNL-induced effects on inorganic nanolayer growth rate, roughening, and stability are germane to realizing high-interface-fraction hybrid nanolaminate multilayers.

Synthesis, Characterization, and Single-Crystal X-ray Structures of Refractory Metal Compounds as Precursors for the Single-Source Chemical Vapor Deposition of Metal Nitrides.

The chemical vapor deposition of refractory metal nitrides requires volatile precursors and has previously been achieved by using metal complexes containing a variety of imide ligands. Recently, the 1,4-di-tert-butyl-1,3-diazabutadiene (DAD) adduct of bis(tert-butylimide)dichloridemolybdenum(VI) was shown to be an excellent precursor for the single-source CVD of Mo2N thin films. Leveraging the success of this work, we prepared chromium and tungsten compounds with the same framework. Additionally, the framework has been modified slightly to allow the isolation of mono(tert-butylimide)trichloride complexes of vanadium, niobium, tantalum, and molybdenum(V) to extend the search for new vapor-phase precursors. These compounds were all fully characterized using the standard methods of multinuclear magnetic resonance spectroscopy, combustion analysis, and single-crystal X-ray diffraction. Their thermal properties were determined by using thermogravimetric analysis and differential scanning colorimetry to assess their utility as vapor-phase precursors. Finally, preliminary deposition studies were carried out to investigate their potential as single-source CVD precursors.

Do the Outcomes of Clinical Efficacy Trials Matter in Regulatory Decision-Making for Biosimilars?

BACKGROUND: There is an increasing body of evidence supporting a more flexible approach in clinical data requirements for the approval of more complex biosimilar substances such as monoclonal antibodies (mAbs). OBJECTIVE: The aim of this paper is to further analyse the role of quality/chemistry, manufacturing and controls (CMC) and clinical data for the conclusion on biosimilarity and the decision on marketing authorisation (MA). METHODS: In the present study, we analysed the MA applications (MAAs) of all 33 mAbs and three fusion proteins evaluated by the European Medicines Agency (EMA) between July 2012 and November 2022 with special emphasis on all submitted rituximab (four products) and trastuzumab (seven products) biosimilar candidates, including withdrawn applications. For the two withdrawn applications, the comparative efficacy trials suggested biosimilarity, but the quality/CMC package was not accepted by EMA. We therefore investigated whether a negative MAA outcome could have been predicted based on the evidence generated in the quality/CMC packages, regardless of clinical trial data. For this purpose, we reviewed the respective European Public Assessment Reports (EPARs) or withdrawal assessment reports, and the first regulatory assessments for all these 36 MAAs (i.e. day 120 of the centralized procedure), which are not publicly available. During EMA review, where significant issues are identified which would preclude a marketing authorisation, these issues are raised as questions to the applicant and are classified as major objections (MO). RESULTS: In 67% of cases, the outcome of the quality and clinical assessment was the same, i.e. both the quality and clinical assessments either supported approval or did not support approval. In 11% of cases, MO were identified in the quality part of the submission but not in the clinical data. In 22% of cases, MO were raised on the clinical data package but not on the quality data. However, we found no instance where seemingly negative clinical data, including failed efficacy trials, led to a negative overall decision. In each instance, the failure to confirm similar clinical performance in all investigated aspects was eventually viewed as not being related to the biosimilar per se but as being due to imbalances in the trial arms, immaturity of secondary endpoint results, change in the reference product, or even chance findings. Furthermore, when performing an in-depth analysis of the quality and clinical packages of trastuzumab and rituximab biosimilars, we found that in no case were clinical trial data necessary to resolve residual uncertainties regarding the quality part. CONCLUSION: The results further support the argument that sufficient evidence for biosimilarity can be obtained from a combination of analytical and functional testing and pharmacokinetic studies which may also generate immunogenicity data. This calls into question the usefulness of comparative efficacy studies for the purposes of regulatory decision-making when approving biosimilar mAbs and fusion proteins.

Disturbance of intermolecular forces: eutectics as a new tool for the preparation of vapor-phase deposition precursors.

The volatile bis(tert-butylimido)dichloromolybdenum(VI) compounds, (tBuN)2MoCl2·dad (dad = 1,4-di-tert-butyl-1,3-diazabutadiene) (1) and [(tBuN)2MoCl(µ-Cl)·(tBuNH2)]2 (2), form a eutectic, with a two to one composition (χ2 = 0.33). A decrease of 40 °C in the melting temperature has been observed between the eutectic mixture and the pure compounds. We have isolated a co-crystal of (tBuN)2MoCl2·dme (dme = 1,2-dimethoxyethane) (3) and 2, also in a two to one ratio, which serves as a structural model for such mixtures. The lower melting point of carefully chosen eutectic mixtures can offer more consistent precursor delivery in deposition processes.

A Data Driven Approach to Support Tailored Clinical Programs for Biosimilar Monoclonal Antibodies.

Biosimilar monoclonal antibodies (mAbs) have been approved in the European Union since 2013 and have been demonstrated to reduce healthcare costs and to expand patient access. Biosimilarity is mainly established on the basis of demonstrated similarity of relevant quality attributes (QAs), determined by comprehensive physiochemical and functional analyses, and demonstration of bioequivalence. In addition, comparative efficacy/safety studies have been requested for all approved biosimilar mAbs so far, although the European Medicines Agency (EMA) Guidelines state that such confirmatory clinical trials may not be necessary in specific circumstances. In order to evaluate the degree of analytical similarity, how residual uncertainty regarding biosimilarity was resolved, and the value of clinical data, we analyzed the quality and clinical data packages for authorized adalimumab (7 products) and bevacizumab (5 products) biosimilars. The percentage of biosimilar batches meeting the similarity range for QAs, as defined by the biosimilar manufacturer based on a comprehensive characterization of the EU reference product (RP), was determined and clinical data were reviewed. Our analyses show that QAs of approved adalimumab and bevacizumab biosimilars have varying concordance with the EU-RP similarity range. In this study, we found that clinical efficacy data played a limited role in addressing quality concerns. Therefore, we encourage a regulatory review of the standards for clinical data requirements for mAb and fusion protein biosimilars. This study outlines a quality data driven approach for facilitating tailored clinical programs for biosimilars.

Origin of Decomposition in a Family of Molybdenum Precursor Compounds.

The bis(tert-butylimido)-molybdenum(VI) framework has been used successfully in the design of vapor-phase precursors for molybdenum-containing thin films, so understanding its thermal behavior is important for such applications. Here, we report the thermal decomposition mechanism for a series of volatile bis(alkylimido)-dichloromolybdenum(VI) adducts with neutral N,N'-chelating ligands, to probe the stability and decomposition pathways for these molecules. The alkyl groups explored were tert-butyl, tert-pentyl, 1-adamantyl, and a cyclic imido (from 2,5-dimethylhexane-2,5-diamine). We also report the synthesis of the new tert-octyl imido adducts, (tOctN)2MoCl2·L (L = N,N,N',N'-tetramethylethylenediamine or 2,2'-bipyridine), which have been fully characterized by spectroscopic techniques as well as single-crystal X-ray diffraction and thermal analysis. We found that the decomposition of all compounds follows the same general pathway, proceeding first by the dissociation of the chelating ligand to give the coordinatively unsaturated species (RN)2MoCl2. Subsequent dimerization results in either an imido bridged adduct, [(RN)Mo(µ-NR)Cl2]2, or a chloride bridged adduct, [(RN)2Mo(µ-Cl)Cl]2, depending on the size of the R group. The dimeric species then likely undergoes an intramolecular γ-hydrogen transfer to yield a nitrido-amido adduct, (RHN)MoNCl2, and an alkene. Ultimately, the resulting molybdenum species appears to decompose into free tert-alkylamine and Mo2N or Mo2C. The thermolysis reactions have been monitored using 1H NMR spectroscopy, and the volatile decomposition products were analyzed using gas chromatography-mass spectrometry. A key intermediate has also been detected using electron ionization high-resolution mass spectrometry. Finally, a detailed computational investigation supports the mechanism outlined above and helps explain the relative stabilities of different N,N'-chelated bis(alkylimido)-dichloromolybdenum(VI) adducts.

Atomic layer deposition of PbCl2, PbBr2 and mixed lead halide (Cl, Br, I) PbXnY2-n thin films.

Atomic layer deposition offers outstanding film uniformity and conformality on substrates with high aspect ratio features. These qualities are essential for mixed-halide perovskite films applied in tandem solar cells, transistors and light-emitting diodes. The optical and electronic properties of mixed-halide perovskites can be adjusted by adjusting the ratios of different halides. So far ALD is only capable of depositing iodine-based halide perovskites whereas other halide processes are lacking. We describe six new low temperature (≤100 °C) ALD processes for PbCl2 and PbBr2 that are crucial steps for the deposition of mixed-halide perovskites with ALD. Lead bis[bis(trimethylsilyl)amide]-GaCl3 and -TiBr4 processes yield the purest, crystalline, uniform and conformal films of PbCl2 and PbBr2 respectively. We show that these two processes in combination with a PbI2 process from the literature deposit mixed lead halide films. The four less optimal processes revealed that reaction by-products in lead halide deposition processes may cause film etching or incorporate themselves into the film.

Thermal Stability and Decomposition Pathways in Volatile Molybdenum(VI) Bis-imides.

The vapor deposition of many molybdenum-containing films relies on the delivery of volatile compounds with the general bis(tert-butylimido)molybdenum(VI) framework, both in atomic layer deposition and chemical vapor deposition. We have prepared a series of (tBuN)2MoCl2 adducts using neutral N,N'-chelates and investigated their volatility, thermal stability, and decomposition pathways. Volatility has been determined by thermogravimetric analysis, with the 1,4-di-tert-butyl-1,3-diazabutadiene adduct (5) found to be the most volatile (1 Torr of vapor pressure at 135 °C). Thermal stability was measured primarily using differential scanning calorimetry, and the 1,10-phenanthroline adduct (4) was found to be the most stable with an onset of decomposition of 303 °C. We have also investigated molybdenum compounds with other alkyl-substituted imido groups: these compounds all follow a similar decomposition pathway, γ-H activation, with varying reaction barriers. The tert-pentyl, 1-adamantyl, and a cyclic imido (from 2,5-dimethylhexane-2,5-diamine) were systematically studied to probe the kinetics of this pathway. All of these compounds have been fully characterized, including via single-crystal X-ray diffraction, and a total of 19 new structures are reported.

Trends and Contributing Factors in Medicolegal Cases Involving Spine Surgery.

STUDY DESIGN: Retrospective descriptive study. OBJECTIVE: The aim of this study was to describe closed medicolegal cases involving physicians and spine surgery in Canada from a trend and patient safety perspective. SUMMARY OF BACKGROUND DATA: Spine surgery is a source of medicolegal complaints against surgeons partly owing to the potential severity of associated complications. In previous medicolegal studies, researchers applied a medicolegal lens to their analyses without applying a quality improvement or patient safety lens. METHODS: The study comprised a 15-year medicolegal trend analysis and a 5-year contributing factors analysis of cases (civil legal and regulatory authority matters) from the Canadian Medical Protective Association (CMPA), representing an estimated 95% of physicians in Canada. Included cases were closed by the CMPA between 2004 and 2018 (trends) or 2014 and 2018 (contributing factors). We fit a linear trend line to the annual rates of spine surgery cases per 1000 physician-years of CMPA membership for physicians in a neurosurgery or orthopedic surgery specialty. We then applied an ANOVA type III sum of squares test to determine the statistical significance of the annualized change rate over time. For the contributing factors analysis, we reported descriptive statistics for patient and physician characteristics, patient harm, and peer expert criticisms in each case. RESULTS: Our trend analysis included 340 cases. Case rates decreased significantly at an annualized change rate of -4.7% (P  = 0.0017). Our contributing factors analysis included 81 civil legal and 19 regulatory authority cases. Most patients experienced health care-related harm (89/100, 89.0%). Peer experts identified intraoperative injuries (29/89, 32.6%), diagnostic errors (14/89, 15.7%), and wrong site surgeries (16/89, 18.0%) as the top patient safety indicators. The top factor contributing to medicolegal risk was physician clinical decision-making. CONCLUSION AND RELEVANCE: Although case rates decreased, patient harm was attributable to health care in the majority of recently closed cases. Therefore, crucial opportunities remain to enhance patient safety in spine surgery.Level of Evidence: 4.

Safety, Immunogenicity and Interchangeability of Biosimilar Monoclonal Antibodies and Fusion Proteins: A Regulatory Perspective.

BACKGROUND: Biosimilars have been used for 15 years in the European Union (EU), and have been shown to reduce costs and increase access to important biological medicines. In spite of their considerable exposure and excellent safety record, many prescribers still have doubts on the safety and interchangeability of biosimilars, especially monoclonal antibodies (mAbs) and fusion proteins. OBJECTIVES: The aim of this study was to analyse the short- and long-term safety and interchangeability data of biosimilar mAbs and fusion proteins to provide unbiased information to prescribers and policy makers. METHODS: Data on the safety, immunogenicity and interchangeability of EU-licensed mAbs and fusion proteins were examined using European Public Assessment Reports (EPARs) and postmarketing safety surveillance reports from the European Medicines Agency (EMA). As recent biosimilar approvals allow self-administration by patients by the subcutaneous route, the administration devices were also analyzed. RESULTS: Prelicensing data of EPARs (six different biosimilar adalimumabs, three infliximabs, three etanercepts, three rituximabs, two bevacizumabs, and six trastuzumabs) revealed that the frequency of fatal treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation of treatment, serious adverse events (SAEs), and main immune-mediated adverse events (AEs) were comparable between the biosimilars and their reference products. The availability of new biosimilar presentations and administration devices may add to patient choice and be an emerging factor in the decision to switch patients. Analysis of postmarketing surveillance data covering up to 7 years of follow-up did not reveal any biosimilar-specific adverse effects. No product was withdrawn for safety reasons. This is in spite of considerable exposure to biosimilars in treatment-naïve patients and in patients switched from the reference medicinal product to the biosimilar. Analysis of data from switching studies provided in regulatory submissions showed that single or multiple switches between the originator and its biosimilar versions had no negative impact on efficacy, safety or immunogenicity. CONCLUSIONS: In line with previous reports of prelicensing studies of biosimilar mAbs and etanercepts, this study demonstrated comparable efficacy, safety, and immunogenicity compared with the reference products. This is the first study to comprehensively analyze postmarketing surveillance data of the biosimilar mAbs and etanercept. An analysis of more than 1 million patient-treatment years of safety data raised no safety concerns. Based on these data, we argue that biosimilars approved in the EU are highly similar to and interchangeable with their reference products. Thus, additional systematic switch studies are not required to support the switching of patients.

Synthesis, Characterization, and Thermal Study of Divalent Germanium, Tin, and Lead Triazenides as Potential Vapor Deposition Precursors.

Only a few M-N bonded divalent group 14 precursors are available for vapor deposition, in particular for Ge and Pb. A majority of the reported precursors are dicoordinated with the Sn(II) amidinates, the only tetracoordinated examples. No Ge(II) and Pb(II) amidinates suitable for vapor deposition have been demonstrated. Herein, we present tetracoordinated Ge(II), Sn(II), and Pb(II) complexes bearing two sets of chelating 1,3-di-tert-butyltriazenide ligands. These compounds are thermally stable, sublime quantitatively between 60 and 75 °C (at 0.5 mbar), and show ideal single-step volatilization by thermogravimetric analysis.

Resolving Impurities in Atomic Layer Deposited Aluminum Nitride through Low Cost, High Efficiency Precursor Design.

A heteroleptic amidoalane precursor is presented as a more suitably designed candidate to replace trimethylaluminum (TMA) for atomic layer deposition of aluminum nitride (AlN). The lack of C-Al bonds and the strongly reducing hydride ligands in [AlH2(NMe2)]3 (1) were specifically chosen to limit impurities in target aluminum nitride (AlN) films. Compound 1 is made in a high yield, scalable synthesis involving lithium aluminum hydride and dimethylammonium chloride. It has a vapor pressure of 1 Torr at 40 °C and evaporates with negligible residual mass in thermogravimetric experiments. Ammonia (NH3) plasma and 1 in an atomic layer deposition (ALD) process produced crystalline AlN films above 200 °C with an Al:N ratio of 1.04. Carbon and oxygen impurities in resultant AlN films were reduced to <1% and <2%, respectively. By using a precursor with a rational and advantageous design, we can improve the material quality of AlN films compared to those deposited using the industrial standard trimethylaluminum and could reduce material cost by up to 2 orders of magnitude.

Case costing in spine surgery: Can surgeons assist with accurate capture of operating room costs?

Surgical case costing is critical for health leaders to make decisions about resource utilization. Synoptic reporting offers the potential for surgeons to capture these costs and work with other leaders to make evidence-based decisions. The purpose of this study was to determine whether surgeons documented intra-operative cost drivers as part of their operative report. This article outlines a synoptic reporting system at a quaternary spine care centre. Data were captured from 2015 to 2020. Surgeon rates of documentation for specific devices, bone graft, and surgical adjuncts were evaluated. It is hoped that the results of this survey will help to guide programs to capture costs in other settings.

Evaluating Factors Contributing to Dropout in a Large Peritoneal Dialysis Program.

BACKGROUND: The low prevalence of peritoneal dialysis (PD) (9%) vs. hemodialysis (HD) (88.2%) is partly due to patient dropout from therapy. METHODS: This retrospective study identified patients who withdrew from PD between 2016 and 2018 in our program. We evaluated all other factors as controllable losses. Analysis included time on therapy at dropout (very early, early or late) and method of initiation (HD to PD conversion, unplanned PD, or planned start). RESULTS: Eighty-three patients enrolled into our PD program. 27 dropped out; 24 were due to controllable factors, 3 due to death, with a median age at dropout of 52 years old. We determined psychosocial factors (PF) to be the largest controllable factor influencing dropout; contributing a 63% rate among all controllable factors. When considering time until dropout, 100% of very early dropout patients and 50% of late dropout patients did so due to PF. Among early dropout patients 67% dropped out due to other medical reasons. The mean time to dropout for PF, other, and infection (INF) were 13, 26, and 33 months, respectively. When considering type of initiation, we found PF to be the largest attributable factor with 50% of unplanned, 100% of planned, and 50% of conversions stopping therapy. CONCLUSIONS: Our study indicates that the primary reason for controllable loss from therapy was secondary to PF regardless of the time on therapy or the method of initiation to therapy.

A Rare Low-Spin CoIV Bis(ß-silyldiamide) with High Thermal Stability: Steric Enforcement of a Doublet Configuration.

Attempted preparation of a chelated CoII ß-silylamide resulted in the unprecedented disproportionation to Co0 and a spirocyclic cobalt(IV) bis(ß-silyldiamide): [Co[(Nt Bu)2 SiMe2 ]2 ] (1). Compound 1 exhibited a room-temperature magnetic moment of 1.8 B.M. and a solid-state axial EPR spectrum diagnostic of a rare S= 1 / 2 configuration for tetrahedral CoIV . Ab initio semicanonical coupled-cluster calculations (DLPNO-CCSD(T)) revealed the doublet state was clearly preferred (-27 kcal mol-1 ) over higher spin configurations only for the bulky tert-butyl-substituted analogue. Unlike other CoIV complexes, 1 had remarkable thermal stability, and was demonstrated to form a stable self-limiting monolayer in preliminary atomic layer deposition (ALD) surface saturation experiments. The ease of synthesis and high stability make 1 an attractive starting point to investigate otherwise inaccessible CoIV intermediates and for synthesizing new materials.

Reaction mechanism of the Me3AuPMe3-H2 plasma-enhanced ALD process.

The reaction mechanism of the recently reported Me3AuPMe3-H2 plasma gold ALD process was investigated using in situ characterization techniques in a pump-type ALD system. In situ RAIRS and in vacuo XPS measurements confirm that the CH3 and PMe3 ligands remain on the gold surface after chemisorption of the precursor, causing self-limiting adsorption. Remaining surface groups are removed by the H2 plasma in the form of CH4 and likely as PHxMey groups, allowing chemisorption of new precursor molecules during the next exposure. The decomposition behaviour of the Me3AuPMe3 precursor on a Au surface is also presented and linked to the stability of the precursor ligands that govern the self-limiting growth during ALD. Desorption of the CH3 ligands occurs at all substrate temperatures during evacuation to high vacuum, occurring faster at higher temperatures. The PMe3 ligand is found to be less stable on a gold surface at higher substrate temperatures and is accompanied by an increase in precusor decomposition on a gold surface, indicating that the temperature dependent stability of the precursor ligands is an important factor to ensure self-limiting precursor adsorption during ALD. Remarkably, precursor decomposition does not occur on a SiO2 surface, in situ transmission absorption infrared experiments indicate that nucleation on a SiO2 surface occurs on Si-OH groups. Finally, we comment on the use of different co-reactants during PE-ALD of Au and we report on different PE-ALD growth with the reported O2 plasma and H2O process in pump-type versus flow-type ALD systems.

Thermal atomic layer deposition of gold nanoparticles: controlled growth and size selection for photocatalysis.

Gold nanoparticles have been extensively studied for their applications in catalysis. For Au nanoparticles to be catalytically active, controlling the particle size is crucial. Here we present a low temperature (105 °C) thermal atomic layer deposition approach for depositing gold nanoparticles on TiO2 with controlled size and loading using trimethylphosphino-trimethylgold(iii) and two co-reactants (ozone and water) in a fluidized bed reactor. We show that the exposure time of the precursors is a variable that can be used to decouple the Au particle size from the loading. Longer exposures of ozone narrow the particle size distribution, while longer exposures of water broaden it. By studying the photocatalytic activity of Au/TiO2 nanocomposites, we show how the ability to control particle size and loading independently can be used not only to enhance performance but also to investigate structure-property relationships. This study provides insights into the mechanism underlying the formation and evolution of Au nanoparticles prepared for the first time via vapor phase atomic layer deposition. Employing a vapor deposition technique for the synthesis of Au/TiO2 nanocomposites eliminates the shortcomings of conventional liquid-based processes opening up the possibility of highly controlled synthesis of materials at large scale.

Seizure-induced thoracolumbar burst fractures - Not to be missed.

While rare, post-ictal thoracolumbar burst fractures are commonly missed due to confounding factors, resulting in delayed treatment and the potential for serious neurological deficits. This paper serves as a call for a high-degree of clinical suspicion when treating post-ictal patients to ensure they undergo a focused neurological examination of the lower extremities. If unresponsive/uncooperative, spinal precautions should be maintained until the spine can be cleared clinically or radiographically. In all events, if the patient is complaining of musculoskeletal pain possibly originating from the spine, radiographic evaluations are warranted to prevent possible deficits caused by a missed thoracolumbar fracture.

Volatile and Thermally Stable Polymeric Tin Trifluoroacetates.

Tin trifluoroacetates are effective vapor phase single-source precursors for F-doped SnO2, but their structures have been poorly understood for decades. Here we undertook a comprehensive structural analysis of these compounds in both the solid and gas phases through a combined single-crystal X-ray crystallography, gas phase electron diffraction, and density functional theory investigation. Tin(II) bis(trifluoroacetate) (1) thermally decomposes into a 1:1 mixture of 1 and ditin(II) µ-oxybis(µ-trifluoroacetate) (2) during sublimation, which then polymerize into hexatin(II)-di-µ3-oxyoctakis(µ-trifluoroacetate) (3) upon solidification. Reversible depolymerization occurred readily upon heating, making 3 a useful vapor phase precursor itself. Tin(IV) tetrakis(trifluoroacetate) (5) was also found to be polymeric in the solid state, but it evaporated as a monomer over 130 °C lower than 3. This counterintuitive improvement in volatility by polymerization was possibly due to the large entropy change during sublimation, which offers a strategic new design feature for vapor phase deposition precursors.

The preliminary opinion of Canadian spine surgeons on Medical Assistance in Dying (MAID); a cross-sectional survey of Canadian Spine Society (CSS) members.

BACKGROUND: On June 17, 2016, providing medical assistance in dying became legal in Canada. This controversial change has had reverberating implications for the entire medical community. This is especially true for physicians that regularly deal with end-of-life decisions, among them neurosurgical and orthopedic spine surgeons, whose patients suffer from a variety of debilitating conditions. With this study we sought to document the opinions of Canadian spine surgeons in hopes of better understanding the sentiment within the speciality towards this change and assess how it evolves over time. METHODS: A cross-sectional survey was sent out to members of the Canadian Spine Society (CSS). The survey encompassed 21 questions pertaining to opinions and attitudes regarding MAID and different facets of the legislation. RESULTS: A total of 51 surgeons responded to the survey, comprised of a mix of orthopedic surgeons (68.6%), pediatric orthopedic surgeons (5.9%), and neurosurgeons (21.6%), practicing all across Canada. The majority support the patients' right to obtain MAID (62.8%) and the right of physicians to participate (82.4%). Most also support the right to conscientious objection (90.1%). The results were split on duty to refer patients for MAID (49.0%). Respondents were also divided on whether they could foresee themselves referring to a MAID service, with 37.2% responding yes. A small minority of respondents (3.9%) felt they could see themselves actively involved in MAID. CONCLUSIONS: At the advent of legal MAID, the majority of members of the CSS supported both the right of patients to participate in MAID and the right of physicians to provide this service if they so choose, while still respecting the principle of conscientious objection. Of note, only a small minority were willing to be actively involved. This survey provides a useful baseline of opinions in this practice area and will be used to analyze changes over the next 10 years.