Operative time and learning curve between fluoroscopy-based instrument tracking and robot-assisted instrumentation for patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF).

INTRODUCTION: Instrument-navigation modalities including CT-guided and robot-assisted methods claim both efficacy and accuracy when applied to spine surgery, yet often increase setup and operating times which can translate to increased costs. To see the impact of different technologies on surgical efficiency, we studied the impact of a single surgeon's experience with a multitude of instrument navigational technologies. METHODS: Consecutive patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) were analyzed. Consecutive cases were done with assistance of a robot (Mazor, Medtronic, Minneapolis, MN), with the assistance of fluoroscopic instrument-tracking (TrackX, North Carolina, USA), or fluoroscopy alone without adjunctive navigation in consecutive blocks of time. The cases done without assistance were used to normalize for number of interbody implants and decompressions performed as well as hardware removal if needed. Age, body mass index (BMI), sex, operative levels, laminectomy, need for hardware removal, and total operative time were recorded. RESULTS: A total of 119 cases (74 conventional, 13 robot-assisted, 32 instrument-tracking) were included in analysis. There were no significant differences in age, sex, or BMI between modalities. Average total operative time for robot-assisted, and instrument-tracking-assisted cases was 175.46 ± 46.86 min 119.63 ± 34.33 min, respectively, for each level (p < 0.05 across each group). After normalization against operative times from similar cases performed with conventional fluoroscopy, robotic-navigation added an average of 42.25 ± 28.35 min while use of instrument-tracking saved an average of 13.88 ± 38.69 min. There was no learning curve seen using robotic navigation, as operative times remained consistently longer than similar cases using conventional fluoroscopy and showed no sign of improvement over time. Cases using instrument-tracking were initially slower but trended downwards through approximately 11 patients, at which point operative times were consistently quicker (R2 = 0.39). None of the assisted cases were abandoned in favor of standard fluoroscopy or required hardware revision. CONCLUSION: Enabling technology can have a significant impact on surgical efficiency. Compared to MIS-TLIFs performed with standard fluoroscopy, those done with robotic-assistance consistently negatively impacted operative times while instrument-tracking was associated with a short learning curve and in the majority of cases studied showed improved operative times.

One Year Outcomes From a Prospective Multicenter Investigation Device Trial of a Novel Conformal Mesh Interbody Fusion Device.

STUDY DESIGN: A prospective multicenter investigational device exempt trial is underway evaluating a novel conformable mesh interbody fusion device in subjects undergoing single-level fusion for degenerative disc disease. Patients meeting inclusion and exclusion criteria were offered enrollment. There is no comparative group in this study. OBJECTIVE: Establish the short and long-term safety and effectiveness of a novel conformable mesh interbody fusion device in subjects undergoing single-level fusion for degenerative disc disease unresponsive to conservative care. SUMMARY OF BACKGROUND DATA: Transforaminal lumbar interbody fusion remains a critical procedure for patients with degenerative lumbar disc disease. Increasingly minimally invasive techniques have been proposed to minimize muscle dissection and tissue damage with the goal of minimizing pain and length of stay. METHODS: One hundred two subjects were enrolled across 10 sites. Ninety nine subjects remained available for follow-up at 12-months. Physical evaluations/imaging were performed serially through 12-months. Validated assessment tools included 100 mm visual analogue scale (VAS) for pain, Oswestry Disability Index (ODI) for function, and computerized tomography scan for fusion. Independent committees were used to identify adverse events and for assessment of radiographic fusion. RESULTS: Reductions in low back pain (LBP)/leg pain and improvements in functional status occur early and are maintained through 12-month follow-up. Mean VAS-LBP change from baseline to 6-weeks post-op (-46 mm) continued to improve through 12 months (-51 mm). Similar trends were observed for leg pain. Mean ODI change from baseline to 6 weeks post-op (-17) was almost doubled by 12 months (-32). Fusion rates at 12-months are high (98%). No device-related serious adverse events have occurred. CONCLUSION: 12-month outcomes demonstrated excellent patient compliance and positive outcomes for pain, function, fusion, and device safety. Clinical improvements were observed by 6-weeks post-op and appear durable up to 1 year later. A novel mesh interbody device may provide an alternative means of interbody fusion that reduces connective tissue disruption.Level of Evidence: 3.

Two-Year Outcomes From a Prospective Multicenter Investigation Device Trial of a Novel Conformal Mesh Interbody Fusion Device.

BACKGROUND: Interbody fusion is a widely utilized and accepted procedure to treat advanced debilitating lumbar degenerative disc disease (DDD). Increasingly, surgeons are seeking interbody devices that are large for stability and grafting purposes but can be inserted with less invasive techniques. To achieve these contrary objectives a novel, conformable mesh interbody fusion device was designed to be placed in the disc space through a small portal and filled with bone graft in situ to a large size. This design can reduce the risk of trauma to surrounding structures while creating a large graft footprint that intimately contours to the patient's own anatomy. The purpose of this Investigational Device Exempt (IDE) trial was to evaluate the perioperative and long-term results of this novel conformable mesh interbody fusion device. METHODS: This investigation is a prospective, multicenter, single-arm, Food and Drug Administration and Institutional Review Board-approved IDE, performance goal trial. A total of 102 adults presenting with DDD at a single level between L2 and S1 and unresponsive to 6 months conservative care had instrumented lumbar interbody fusion. Validated assessment tools include 100 mm visual analog scale for pain, Oswestry Disability Index (ODI) for function, single question survey for patient satisfaction, and computed tomography (CT) scan for fusion. Patients were enrolled across 10 geographically distributed sites. Pain/ODI surveys, physical evaluations, and imaging were performed serially through 24 months. Specifically, CT was performed at 12 and, if not fused, 24 months. Independent radiologists assessed CTs for fusion. An independent committee adjudicated adverse events. Patients with complete data at 24 months were included in the analysis. RESULTS: Ninety-six (96, 94% follow-up rate) patients (57.0 ± 12.0 years, 50.0% female, Body Mass Index 30.6 ± 4.9) reported average decreased low back pain from baseline of 45.0 ± 26.6 at 6 weeks and 51.4 ± 26.2 at 24 months. Right/left leg pain reduced by 28.9 ± 36.7/37.8±32.4 at 6 weeks and 30.5±33.0/40.3 34.6 at 24 months. Mean ODI improved 17.1 ± 18.7 from baseline to 6 weeks and 32.0 ± 18.5 by 24 months. At 24 months, 91.7% of patients rated their procedure as excellent/good. Fusion rates were 97.9% (94/96) at 12 months, and 99% (95/96) at 24 months. Mean operative time, estimated blood loss, and length of stay were 2.6 ± 0.9 hours, 137 ± 217 mL, and 2.3 ± 1.2 days, respectively. No device-related serious adverse events have occurred. CONCLUSIONS: Clinically significant outcomes for pain, function, fusion, and device safety were demonstrated in this population. Substantial clinical improvements occur by 6 weeks postoperative and continue to improve to 24 months. The successful outcomes observed in this trial support use of this novel device in an instrumented lumbar interbody fusion. LEVEL OF EVIDENCE: 3. CLINICAL RELEVANCE: This reports substantiates that the preliminary 1-year findings published earlier for this investigation are confirmed and the fusion rates and that patient improvements reported are sustained through 2 years.

Incidence of sexually transmitted infections before and after preexposure prophylaxis for HIV.

OBJECTIVE: Use of preexposure prophylaxis (PrEP) for HIV raises concerns about sexually transmitted infection (STI) incidence because of decreased condom use among MSM. This study examines whether PrEP is associated with STIs in the 12 months following PrEP prescription relative to the 12 months prior to PrEP and if STI rates are higher among PrEP users relative to individuals receiving postexposure prophylaxis (PEP). DESIGN: Retrospective cohort study including PrEP users with more than 12 months of follow-up before PrEP prescription and individuals receiving PEP from 2010 to 2015 at Clinique l'Actuel (Montréal, Canada). METHODS: Incidence of chlamydia, gonorrhoea, syphilis and hepatitis C virus over 12 months was compared before and after PrEP; and for PrEP versus PEP users using Poisson models to generate incidence rate ratios (IRRs) with 95% confidence intervals (CIs) and adjusted IRRs (aIRRs) controlling for frequency of STI-screening visits. Models comparing PrEP and PEP users were further adjusted for age and education. RESULTS: One hundred and nine PrEP and 86 PEP users were included. Increased rates of STIs were observed in the 12 months after PrEP relative to the 12 months prior (IRR: 1.72, CI: 1.22-2.41; aIRR: 1.39, CI 0.98-1.96). PrEP users were also at higher STI risk relative to PEP users (IRR: 2.18, CI: 1.46-3.24; aIRR: 1.76, CI: 1.14-2.71). CONCLUSION: Increased rates of STIs among individuals after initiation of PrEP may suggest greater risk behaviours during the first year on PrEP. Further studies are needed to measure long-term trends in STI acquisition following PrEP initiation.

An exploration of factors associated with post-traumatic stress in ER nurses.

BACKGROUND: Emergency room (ER) nurses are frequently exposed to traumatic events (TE) at work. These events can lead to symptoms of post-traumatic stress disorder (PTSD). AIM: The goal of the present study was to describe the factors associated with PTSD symptoms. METHODS: A cross-sectional descriptive correlational design was used. The sample consisted of 35 nurses from an ER in Québec (Canada). Data were collected through self-administered questionnaires. RESULTS: TEs presenting a grief component (e.g. intentional injury to a child and patient suicide) are positively associated with peritraumatic distress (PD) in the days after the event. PD is positively associated with PTSD symptoms. Two personality traits (neuroticism and extraversion) should also be considered. Neuroticism is positively associated with PD whereas extraversion is negatively associated with PD and PTSD symptoms. CONCLUSION: The results are consistent with the literature, but some of these results are new to nurses. They suggest that in this population, TEs in the ER represent 'red flags'. Their occurrence should mobilise support structures. PD and its personality traits are also key factors to consider. IMPLICATION FOR NURSING MANAGEMENT: To provide adequate support for nurses, ER managers should be on the alert for these conditions. Interventions should be adapted to these findings.

Removing inactive NRTIs in a salvage regimen is safe, maintains virological suppression and reduces treatment costs: results from the VERITAS study (TMC114HIV4054).

BACKGROUND: Despite the benefit of maintaining inactive Nucleotide/side reverse transcriptase inhibitors (NRTIs) in salvage regimens, they are associated with increased toxicity and treatment costs. Current evidence suggests that NRTI-sparing regimens in patients failing ART are non-inferior to NRTI-including regimens. This study aimed to evaluate the impact of removing at least one inactive NRTI on virologic, safety, and financial outcomes. METHODS: Drug-resistant, virologically suppressed patients with CD4 >250 cells/ml on a stable regimen of four or more antiretrovirals (ARVs) were enrolled in a 48-week prospective, open-label pilot trial. One inactive NRTI was removed at baseline. Patients taking over five ARVs had a second inactive NRTI removed at 24 weeks. Viral load, CD4 count, and adverse events were assessed at baseline, 24, and 48 weeks. RESULTS: Thirty-one male patients participated. Twenty-nine (94%) patients had lamivudine (3TC) or emtricitabine (FTC) removed and four patients had an additional NRTI removed. One patient was excluded at week 26 for discontinuing an active NRTI. All patients maintained undetectable viral loads at weeks 24 (100%) and 48 [PP = 100%; Intent-to-treat (ITT) = 97%]. At 48 weeks, patients had a median gain of 20 CD4 (IQR: - 50, +133; mean +39) compared to baseline. Three patients exhibited Grade III bilirubin elevation (two Grade II and one Grade III at baseline), which returned to baseline levels. No serious adverse events were observed. Removal of one or two ARVs equated to a mean annual savings of $3319 CDN (11%) and $8630 CDN (24%), respectively. CONCLUSION: Removing inactive NRTIs in patients with a controlled viral load appears to be safe, maintains virological suppression, and reduces treatment costs.

Tolerability is more important than simplicity for treatment durability.

INTRODUCTION: Many studies have shown the superiority of single tablet regimens (STRs) of antiretrovirals for the treatment of HIV in terms of efficacy, adherence and rate of hospitalisation as they offer a low pill burden and once daily dosing. Our objective was to compare the duration of first-line STRs to multi-tablet regimens. METHODS: From our clinical database, we selected patients initiating any of the major first-line regimens between 2007 and 2013. Two STRs, Atripla (ATP) and Complera (CPLR), were compared to three non-STRs: two NRTIs and raltegravir (RAL), atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r). The primary outcome was time to discontinuation of the first-line regimen. The association between regimen type and duration was estimated using Cox proportional hazards models adjusted for age, gender, baseline CD4, baseline viral load, risk factor, site and year of treatment initiation. RESULTS: A total of 743 patients (281 on STRs and 462 on non-STRs) were included. 693 (93%) were male and median age was 43 years. Median length of follow-up was 3.2 years. 56% of patients were MSM, 6% IDU and 6% from endemic countries. Patients on an STR were less likely to be IDU (p<0.024) and have a baseline HIV-RNA ≥100,000 copies/mL (p<0.011). Overall, 321 (43%) patients discontinued their regimen during the study period. The rate of discontinuation one year after starting ARV depends on the regimen: 29% for patients on 2NRTIs+DRV/r, 26% on ATP, 25% on 2NRTIs+ATV/r, 17% on 2NRTIs+RAL and 10% on CPLR (p<0.001). In the adjusted model, durability for STR and non-STR was equivalent (aHR=0.83, p=0.108). Compared to patients on ATP, patients on CPLR were less likely to discontinue (HR=0.58, p=0.070). No difference between ATP and the other regimens was observed: HR for 2NRTIs+RAL=0.92 (p=0.66), 2NRTIs+ DRV/r=1.16 (p=0.36), 2NRTIs+ATV/r=1.11 (p=0.46). CONCLUSIONS: Our findings suggest that STRs do not necessarily result in a more durable treatment. Even with a higher pill burden and/or twice daily dosing, patients initiating therapy with RAL or boosted-PI based regimens were not more likely to discontinue the first-line regimen compared to patients on an STR. Among the STR subgroups, the regimen with better known tolerability conferred more durable treatment. Limitations included our inability to adjust for the patient's adherence to a given regimen.

Removing inactive NRTIs in a salvage regimen is safe, maintains virological suppression and reduces treatment costs: 96 weeks post VERITAS study.

INTRODUCTION: In HIV+ patients exhibiting multidrug resistance (MDR), NRTIs often have little activity, increased toxicity, drug interactions and add unnecessary treatment costs. The 48 week VERITAS study demonstrated that these patients can have a safe and effective simplification of salvage regimen by removing inactive NRTIs as determined by genotypic data. Virological, immunological, clinical and financial outcomes were evaluated at an additional 96 weeks of follow-up. MATERIALS AND METHODS: MDR patients with an undetectable viral load (VL) on a stable regimen containing at least four ARVs (including one inactive NRTI) were enrolled in an open-label, prospective simplification trial, where one inactive NRTI was removed at baseline (BL). A second NRTI could be removed at week 24 if the regimen contained at least five ARVs at enrolment. RESULTS: 31 male patients participated. The mean length of treatment was 14 years, with a median CD4 count of 525. The BL regimen consisted of 4 ARVs in 22 patients (71%) and 5 ARVs in 9 patients (29%). 3TC or FTC was removed in 29 patients (94%), and either AZT or TDF was interrupted in 2 others. Four patients had a second NRTI stopped. One patient was removed at W26 as an active NRTI was removed for creatinine elevation. 30 well-controlled patients continued follow-up after W48. At W144, six patients had additional changes in their ARV regimen. Half were due to toxicity (jaundice, neuropathy and nephrotoxicity) while the other half were the result of treatment simplification. None of the patients exhibited virologic failure at the time of treatment change and maintained undetectable VLs throughout the entire follow-up. These six patients had a mean gain of 79 CD4 (p=0.17) compared to baseline. 22 of the 24 patients (92%) with no changes in ARV therapy after W48 had undetectable VLs. The other two had confirmed virologic failure, one with genotypic resistance. All 24 had elevated CD4 counts (mean +118 CD4, p<0.0001). No deaths or serious adverse events were observed. One or two ARV removals translated to a mean annual saving of $3319 CDN (11%) and $8630 (24%) respectively. CONCLUSIONS: Final results indicate that removing one or two inactive NRTIs from a regimen in patients taking four or more ARVs with controlled VL appears to be safe, maintains virological suppression through 144 weeks and significantly reduces treatment costs.

Abacavir/lamivudine fixed-dose combination with ritonavir-boosted darunavir: a safe and efficacious regimen for HIV therapy.

BACKGROUND: Current treatment guidelines recommend the use of tenofovir (TDF) and emtricitabine (FTC) along with a third agent to treat HIV-positive adults. However, other treatment options, including the use of abacavir (ABC) and lamivudine (3TC) when used with ritonavir-boosted darunavir (DRV/r), have rarely been studied. OBJECTIVE: We evaluated the safety and efficacy of the coformulation of ABC/3TC administered with DRV/r in treatment-naïve and treatment-experienced patients. METHODS: HIV-infected adults who received an open-label combination of ABC/3TC/ DRV/r were followed in a community clinic in Montréal. Patients had no resistance to any of the compounds in their regimen. Viral load (VL), CD4 cell count, AST, ALT, and creatinine levels were examined throughout the 48 weeks of follow-up. RESULTS: Sixty-seven patients with a mean age of 45 years were enrolled. Two did not return for follow-up and were excluded. Thirty-five (52%) were treatment- experienced and the remaining were treatment-naïve. HLA-B*5701 test results were available for 56 patients and none were positive. At baseline, mean VL was 4.8 log for treatment-naïve and 2.3 log for experienced patients. Twelve patients discontinued the study regimen prior to reaching the endpoint. At week 48, 79% had a VL <50. Median CD4 cell gain was higher among treatment-naïve patients (273 cells) than among treatment-experienced patients (102 cells) (P = .002). No patient experienced any grade 2 or higher liver enzyme elevation throughout the study. CONCLUSIONS: The new combination of ABC/3TC/DRV/r demonstrates a high rate of antiviral activity with no major toxicity. The drug combination appears to be generally safe and well tolerated.

Direct observation of molecular preorganization for chirality transfer on a catalyst surface.

The chemisorption of specific optically active compounds on metal surfaces can create catalytically active chirality transfer sites. However, the mechanism through which these sites bias the stereoselectivity of reactions (typically hydrogenations) is generally assumed to be so complex that continued progress in the area is uncertain. We show that the investigation of heterogeneous asymmetric induction with single-site resolution sufficient to distinguish stereochemical conformations at the submolecular level is finally accessible. A combination of scanning tunneling microscopy and density functional theory calculations reveals the stereodirecting forces governing preorganization into precise chiral modifier-substrate bimolecular surface complexes. The study shows that the chiral modifier induces prochiral switching on the surface and that different prochiral ratios prevail at different submolecular binding sites on the modifier at the reaction temperature.

Thermal chemistry of methylene- and phenyl-functionalized carbon nanotubes.

Thermal desorption of covalently functionalized SWNT was followed using Raman, X-ray photoemission (XPS), and thermodesorption (TDS) spectroscopies. By functionalizing different sources of SWNT, we assess the thermal stability of phenyl- and methylene-SWNT derivatives in relation to the source diameter and helicity distribution. For all samples, broad desorption features were observed at approximately 600 K for the phenyl-SWNT and at approximately 500 K for the methylene-SWNT derivatives. In both cases, no influence on helicity and on diameter was observed for the range studied. The study shows that the stability of methylene addends on SWNT is inferior to that of the phenyl and proves that the main desorption pathway of phenyl addends is a phenyl-phenyl coupling reaction.

Activation in prochiral reaction assemblies on Pt(111).

Trifluoroacetophenone (TFAP) forms C O...H-C bonded dimers and trimers at room temperature on Pt(111). It is proposed that these systems mimic the prochiral carbonyl-chiral modifier interaction in the enantioselective hydrogenation of TFAP on cinchona-modified Pt catalysts. That is, the activation of TFAP in homomolecular assemblies at racemic sites is expected to be roughly the same as in the diastereomeric complex formed at chiral sites. This interpretation suggests a reason why alpha-phenyl ketones do not display a strong measured rate enhancement effect in the Orito reaction.

A generalized two-point H-bonding model for catalytic stereoselective hydrogenation of activated ketones on chirally modified platinum.

The asymmetric hydrogenation of alpha-ketoesters on cinchona-modified supported platinum particles is a prototype reaction in heterogeneous chiral catalysis. The catalysis literature shows that the reaction is highly metal-specific, that it displays rate-enhancement with respect to the racemic reaction on the nonmodified surface, and that the observed stereoselectivity is a sensitive function of substrate and modifier structure. This set of observations has proven difficult to rationalize within the context of existing models for the mechanism of the Orito reaction. The most widely discussed mechanistic models are based on the formation of chemisorbed 1:1 complexes through H-bonding between the quinuclidine function of the cinchona modifier and the prochiral, keto-carbonyl, function of the substrate. Recent surface science studies, as well as advances in the area of C-H...O hydrogen bonding, suggest that chemisorption-induced polarization may lead to an aromatic-carbonyl H-bonding interaction between the aromatic anchor of the modifier and the coadsorbed substrate. By specifying that the aromatic C-H...O interaction is to the prochiral carbonyl and that it is accompanied by a H-bonding interaction between the ester carbonyl and the quinuclidine function, we show that it is possible to rationalize essentially all of the catalysis literature for the Orito reaction in terms of a single molecular mechanism. The generality of the proposed mechanistic model is demonstrated by addressing data from the literature for a representative range of substrates, modifiers, solvents, and metals. Results of catalytic tests on an asymmetric diketone substrate are presented in support of the model.

Evidence for C-H...O=C bonding in coadsorbed aromatic-carbonyl systems on Pt(111).

The coadsorption of ethyl formate, acetone, and methyl pyruvate with benzene and naphthalene on Pt(111) was studied with reflection absorption infrared spectroscopy (RAIRS) and thermal desorption (TPD) measurements. Coadsorbed benzene or naphthalene are found to convert eta1- and eta2-states of ethyl formate and acetone into new states displaying slightly red-shifted carbonyl bands. Similarly, coadsorption converts the enediolate state of methyl pyruvate into a new adsorption geometry in which the carbonyl bands are silent. In each case, coadsorption of the aromatic leads to significantly modified carbonyl desorption spectra. The results suggest an attractive carbonyl-aromatic interaction that weakens or removes the direct interaction of the carbonyl function with the metal surface. The aromatic-carbonyl interaction is attributed to hydrogen bonding between C-H and C=O, enhanced by the chemisorption induced polarization of the aromatic.

Load sharing and kinematics of threaded cages for lumbar interbody fusion.

The load-sharing characteristics of threaded interbody cages before and after cyclic loading are poorly understood. In the current study, lumbar interbody cages were filled with epoxy, sectioned longitudinally, and pressure sensors were placed between halves of the cages to measure the distribution of loads between and within the cages. Human lumbar spine segments were instrumented anteriorly with bilateral cages and subjected to cyclic compression loads combined with flexion and extension moments. Sagittal plane motion between vertebrae on either side of the cages also was measured during application of cyclic compression and flexion loads. A small but statistically significant asymmetry was found in the distribution of load between the left and right cages, and the extent of asymmetry varied during compression and flexion loading. With ligament tension only, 66% of the load was supported by the posterior regions of the cages, whereas during peaks in the combined compression and flexion loading, only 33% of the load was supported by the posterior regions. The cages reduced intervertebral motion 78% during forward flexion, whereas extension resulted in a 100% increase in motion. Surgeons should recognize that bilateral cages may not share loads equally, and the results of this study suggest that early extension should be restricted after the placement of anterior lumbar interbody cages.