Recurrent Instability after Arthroscopic Glenoid Labral Repair with a Minimum of Three Points of Fixation: Do the Number of Anchors or Fixation Points Correlate to Outcomes?

INTRODUCTION: The goal of this study was to evaluate the recurrence rate of instability following arthroscopic Bankart repairs in regard to the number and types of fixation utilized. A Bankart lesion is a tear in the anteroinferior capsulolabral complex within the shoulder, occurring in association with an anterior shoulder dislocation. These injuries can result in glenoid bone loss, decreased range of motion, and recurrent shoulder instability. Successful repair of these lesions has been reported in the literature with repair constructs that have three points of fixation. However, the definition of "one point of fixation" is yet to be fully elucidated. MATERIALS AND METHODS: A consecutive series of arthroscopically repaired Bankart lesions were evaluated pertaining to the points of fixation required to achieve shoulder stability. This included the number, position, and types of anchors used. Patients consented to complete a series of surveys at a minimum of two years postoperatively. The primary outcome was to determine recurrent instability via the UCLA Shoulder Score, the ROWE Shoulder Instability Score, and the Oxford Shoulder Score. A secondary outcome included pain on a Visual Analog Scale (VAS). RESULTS: There were 116 patients reviewed, 46 patients achieved three points of fixation in their surgical repair via two anchors and 70 patients achieved a similar fixation with three or more anchors. There was no significant difference in the mean age, gender, or body mass index (BMI). Patients receiving two anchors demonstrated recurrent instability 8.7% of the time (4 of 46 patients). Patients who received three or more anchors demonstrated recurrent instability 8.6% of the time (6 of 70 patients). Overall, there was no statistical significance between the number/types of anchors used. Between the two cohorts, there was no statistically significant difference found between VAS, ROWE, UCLA, and Oxford Scores. There was a significant difference in pain reported on the VAS scale with an average VAS score of 0.43 versus 2.5 in those without and with recurrent instability respectively. CONCLUSION: Contention still exists surrounding the exact definition of "a point of fixation" in arthroscopic Bankart repairs. Three-point constructs can be created through a variety of combinations including anchors and sutures, ultimately achieving the goal of a stable shoulder.

An observational study of rotigotine transdermal patch and other currently prescribed therapies in patients with Parkinson's disease.

Real-world data from large cohorts of patients with Parkinson's disease on the long-term effectiveness of different dopamine-substituting drug therapies are rare. The objective of this study was to obtain information on real-world management of PD with dopamine-substituting drugs. SP0854 (NCT00599339) was a prospective, multicenter, non-interventional, multiple-cohort, post-authorization safety study of rotigotine versus other dopaminergic therapies. The study was also part of a European Medicines Agency risk-management plan for the non-ergoline dopamine agonist rotigotine, focussing on cardiovalvular fibrosis. Eligible patients requiring monotherapy with a dopamine agonist, or levodopa in combination with a dopamine agonist were followed for ≤ 33 months; 1531 of 2195 patients completed the study. Mean motor scores improved for all dopamine-substituting treatments. Patients with more severe motor-symptoms/increased disability were more likely to receive levodopa alone or in combination with a DA at study onset. More patients who started on combination therapy with levodopa remained on this treatment versus those starting on dopaminergic monotherapy. This real-world study showed that the dopamine-substituting therapies were efficacious, with a safety profile consistent with that expected of dopaminergic treatments. Cardiovalvular pathology was rare and not found to be causally-related to rotigotine.

Asynchronous movements prior to pore opening in NMDA receptors.

Glutamate-gated ion channels embedded within the neuronal membrane are the primary mediators of fast excitatory synaptic transmission in the CNS. The ion channel of these glutamate receptors contains a pore-lining transmembrane M3 helix surrounded by peripheral M1 and M4 helices. In the NMDA receptor subtype, opening of the ion channel pore, mediated by displacement of the M3 helices away from the central pore axis, occurs in a highly concerted fashion, but the associated temporal movements of the peripheral helices are unknown. To address the gating dynamics of the peripheral helices, we constrained the relative movements of the linkers that connect these helices to the ligand-binding domain using engineered cross-links, either within (intra-GluN1 or GluN2A) or between subunits. Constraining the peripheral linkers in any manner dramatically curtailed channel opening, highlighting the requirement for rearrangements of these peripheral structural elements for efficient gating to occur. However, the magnitude of this gating effect depended on the specific subunit being constrained, with the most dramatic effects occurring when the constraint was between subunits. Based on kinetic and thermodynamic analysis, our results suggest an asynchrony in the displacement of the peripheral linkers during the conformational and energetic changes leading to pore opening. Initially there are large-scale rearrangements occurring between the four subunits. Subsequently, rearrangements occur within individual subunits, mainly GluN2A, leading up to or in concert with pore opening. Thus, the conformational changes induced by agonist binding in NMDA receptors converge asynchronously to permit pore opening.

Antipsychotic adherence patterns and health care utilization and costs among patients discharged after a schizophrenia-related hospitalization.

BACKGROUND: This study aimed to assess antipsychotic adherence patterns and all-cause and schizophrenia-related health care utilization and costs sequentially during critical clinical periods (i.e., before and after schizophrenia-related hospitalization) among Medicaid-enrolled patients experiencing a schizophrenia-related hospitalization. METHODS: All patients aged ≥ 18 years with a schizophrenia-related inpatient admission were identified from the MarketScan Medicaid database (2004-2008). Adherence (proportion of days covered [PDC]) to antipsychotics and schizophrenia-related and all-cause health care utilization and costs were assessed during preadmission (182- to 121-day, 120- to 61-day, and 60- to 0-day periods; overall, 6 months) and postdischarge periods (0- to 60-day, 61- to 120-day, 121- to 180-day, 181- to 240-day, 241- to 300-day, and 301- to 365-day periods; overall, 12 months). Health care utilization and costs (2010 US dollars) were compared between each adjacent 60-day follow-up period after discharge using univariate and multivariable regression analyses. No adjustment was made for multiplicity. RESULTS: Of the 2,541 patients with schizophrenia (mean age: 41.2 years; 57% male; 59% black) who were identified, approximately 89% were "discharged to home self-care." Compared with the 60- to 0-day period before the index inpatient admission, greater mean adherence as measured by PDC was observed during the 0- to 60-day period immediately following discharge (0.46 vs. 0.78, respectively). The mean PDC during the overall 6-month preadmission period was lower than during the 6-month postdischarge period (0.53 vs. 0.69; P < 0.001). Compared with the 0- to 60-day postdischarge period, schizophrenia-related health care costs were significantly lower during the 61- to 120-day postdischarge period (mean: $2,708 vs. $2,102; P < 0.001); the primary cost drivers were rehospitalization (mean: $978 vs. $660; P < 0.001) and pharmacy (mean: $959 vs. $743; P < 0.001). Following the initial 60-day period, both all-cause and schizophrenia-related costs declined and remained stable for the remaining postdischarge periods (days 121-365). CONCLUSIONS: Although long-term (e.g., 365-day) adherence measures are important, estimating adherence over shorter intervals may clarify the course of vulnerability to risk and enable clinicians to better design adherence/risk-related interventions. The greatest risk of rehospitalization and thus greater resource utilization were observed during the initial 60-day postdischarge period. Physicians should consider tailoring management and treatment strategies to help mitigate the economic and humanistic burden for patients with schizophrenia during this period.

Long-acting injectable paliperidone palmitate versus oral paliperidone extended release: a comparative analysis from two placebo-controlled relapse prevention studies.

BACKGROUND: Increasing availability and use of long-acting injectable antipsychotics have generated a need to compare these formulations with their oral equivalents; however, a paucity of relevant data is available. METHODS: This post hoc comparison of the long-term efficacy, safety and tolerability of maintenance treatment with paliperidone palmitate (PP) versus oral paliperidone extended release (ER) used data from two similarly designed, randomised, double-blind (DB), placebo-controlled schizophrenia relapse prevention trials. Assessments included measures of time to relapse, symptom changes/functioning and treatment-emergent adverse events (TEAEs). Time to relapse between treatment groups was evaluated using a Cox proportional hazards model. Between-group differences for continuous variables for change scores during the DB phase were assessed using analysis of co-variance models. Categorical variables were evaluated using Chi-square and Fisher's exact tests. No adjustment was made for multiplicity. RESULTS: Approximately 45% of enrolled subjects in both trials were stabilised and randomised to the DB relapse prevention phase. Risk of relapse was higher in subjects treated with paliperidone ER than in those treated with PP [paliperidone ER/PP hazard ratio (HR), 2.52; 95% confidence interval (CI), 1.46-4.35; p < 0.001]. Similarly, risk of relapse after withdrawal of paliperidone ER treatment (placebo group of the paliperidone ER study) was higher than after withdrawal of PP (paliperidone ER placebo/PP placebo HR, 2.25; 95% CI, 1.59-3.18; p < 0.001). Stabilised schizophrenic subjects treated with PP maintained functioning demonstrated by the same proportions of subjects with mild to no difficulties in functioning at DB baseline and end point [Personal and Social Performance (PSP) scale total score >70, both approximately 58.5%; p = 1.000] compared with a 10.9% decrease for paliperidone ER (58.5% vs 47.6%, respectively; p = 0.048). The least squares mean change for Positive and Negative Syndrome Scale (PANSS) total score at DB end point in these previously stabilised subjects was 3.5 points in favour of PP (6.0 vs 2.5; p = 0.025). The rates of TEAEs and AEs of interest appeared similar. CONCLUSIONS: This analysis supports maintenance of effect with the injectable compared with the oral formulation of paliperidone in patients with schizophrenia. The safety profile of PP was similar to that of paliperidone ER. Future studies are needed to confirm these findings.

A Novel Multimodal Postoperative Pain Protocol for 1- to 2-Level Open Lumbar Fusions: A Retrospective Cohort Study.

BACKGROUND: There has been increased interest in exploring methods to reduce postoperative pain without opioid medications. In 2015, a multimodal analgesia protocol was used involving the perioperative use of celecoxib, gabapentin, intravenous acetaminophen, lidocaine, and liposomal bupivacaine. Overall, the goal was to reduce the utilization of scheduled opioids in favor of nonopioid pain management. METHODS: The results of a consecutive series of 1- to 2-level open primary lumbar fusions were compared to a cohort of patients after the implementation the perioperative multimodal pain management protocol. Primary endpoints included patient-reported pain scores and secondary endpoints included length of stay. RESULTS: There were 87 patients in the preprotocol cohort and 184 in the protocol cohort. Comparing protocol and preprotocol patients, there were no significant differences in patient demographics. There was significantly average lower pain in the protocol group on postoperative day (POD) 1 (4.50 vs 5.00, P < 0.02) and POD2 (4.42 vs 5.50, P < 0.03). There was a lower pain score on POD0 (4.80 vs 5.00), but it was only clinically significant. There was a correlation between pain and duration of surgery in the preprotocol patients (POD0 R = 0.23, POD1 R = 0.02, POD2 R = 0.38), but not in the protocol patients (POD0 R = -0.05, POD1 R = -0.08, POD2 R = -0.04). There was a shorter length of stay in the protocol cohort (2.0 vs 3.0, P < 0.01). Finally, there was an approximately 35% reduction in morphine milligram equivalents of opioids in the protocol vs preprotocol cohorts (36.2 vs 57.0, P < 0.05). CONCLUSION: Our novel multimodal pain management protocol significantly reduced postoperative pain, length of stay, and opioid consumption in this patient cohort. Opioid usage correlated to pain in the protocol patients, while the preprotocol patients had no correlation between opioid use and pain medication. CLINICAL RELEVANCE: In this study, we demonstrated that preoperative and intraoperative analgesia can reduce postoperative pain medication requirements. Furthermore, we introduced a novel concept of a correlation of pain with opioid consumption as a marker of effective pain management of breakthrough pain.

Predatory Publishing Practices.

With open access publishing surging in popularity, it has provided an opportunity for entities to take advantage of the unique business model. Known as predatory journals, these entities accept a large fee in exchange for publication, but do not maintain any form of standards or peer review. This article aims to introduce the history and rise of predatory journals in hopes to further raise awareness and limit their spread.

Household Transmission of Group A Streptococcus Necrotizing Fasciitis.

A healthy 40-year-old woman was diagnosed with necrotizing fasciitis 2 days after her husband's death from the same infectious process. Prompt identification and immediate surgical intervention prevented a similar result in this patient. Additional investigation into both patients' medical records found the inciting organism to be group A streptococcus. Although the exact mechanism of inoculation is unknown, the spread of this infection within a household prompts the question of whether antibiotic prophylaxis should be given among close contacts in future cases of necrotizing fasciitis.

Burnout Rates Among General Orthopedic Surgeons and Subspecialists: A Pilot Study.

Burnout among physicians is a syndrome of emotional exhaustion, de-personalization, and reduced sense of personal accomplishment that can negatively affect personal relationships, physician well-being, and patient outcomes. Although burnout rates of up to 50% to 60% among orthopedic surgeons have been reported, no studies have evaluated burnout among orthopedic generalists and subspecialists. The primary goal of this study was to examine the prevalence of burnout among orthopedic disciplines. We conducted a multicenter study from March 2019 through December 2019 involving 149 orthopedists. An abbreviated Maslach Burnout Inventory-Human Services Survey was used to measure burnout. Demographic information, personal characteristics, professional characteristics, family life and spousal support, and depression were also assessed. The mean rate of burnout among all respondents was 62%, whereas 16.77% screened positive for depression. Subspecialties with the highest rates of burnout were oncology (100%), sports medicine (68%), and trauma (63%). Similarly, trauma (50.00%), oncology (40.00%), and general orthopedics (20.00%) had the highest positive depression screening rates. In contrast, shoulder and elbow (50%), pediatric (52%), and foot and ankle (54%) specialists had the lowest rates of burnout, whereas shoulder and elbow (0.00%), spine (0.00%), and sports medicine (6.50%) specialists had the lowest rates of positive depression screening. Older age, higher debt load, and oncology subspecialty were associated with increased burnout risk. This study sought to determine burnout rates within each orthopedic discipline, with a secondary aim of disclosing contributing factors. Trauma and oncology had the highest rates of burnout and positive depression screening. Because this study represents a small orthopedic cohort, larger studies are needed to appropriately manage burnout in the future. [Orthopedics. 2022;45(6):333-339.].

Perioperative Chanage in Cervical Lordosis and Health-Related Quality-of-Life Outcomes.

BACKGROUND: Surgeons have scrutinized spinal alignment and its impact on improving clinical outcomes following anterior cervical discectomy and fusion (ACDF). The primary analysis of this study examines the relationship between change in perioperative cervical lordosis (CL) and health-related quality-of-life (HRQOL) outcomes after ACDF. Secondary analysis evaluates the effects of fusion construct length on outcomes in patients grouped by preoperative cervical alignment. METHODS: A retrospective cohort study was performed on an institutional database including patients who underwent 1- to 3-level ACDF. C2-C7 CL was measured preoperatively and at final follow-up. For primary analysis, patients were classified based on their perioperative cervical lordotic correction: (1) kyphotic, (2) maintained, and (3) restored. For secondary analysis, patients were categorized based on their preoperative C2-C7 CL: (1) kyphotic, (2) neutral, and (3) lordotic. Demographics and perioperative change in patient-reported outcome measures were compared between groups. RESULTS: A total of 308 patients were included. A significant difference was noted among maintained, restored, and kyphotic groups in terms of delta physical compositeshort form-12 score (ΔPCS-12) (9.0 vs 10.3 vs 1.5; P = 0.04) and delta visual analog scale score (ΔVAS) for arm pain (-0.9 vs -3.8 vs -0.6; P = 0.03). Regression analysis revealed significantly greater improvement of PCS-12 (ß: 8.6; P = 0.03) and VAS arm (ß: -2.0; P = 0.03) scores in restored patients compared with kyphotic patients. The length of fusion construct in patients grouped by preoperative cervical alignment had no significant impact on the clinical outcomes on regression analysis. CONCLUSIONS: Significantly greater PCS-12 and VAS arm improvement were seen in patients whose cervical sagittal alignment was restored to neutral/lordotic compared with those who remained kyphotic. Multivariate analysis demonstrated no association between construct length and perioperative outcomes. CLINICAL RELEVANCE: The results of this study highlight the importance of sagittal alignment and restoration of CL after short-segment ACDF. Irrespective of preoperative sagittal alignment, the length of ACDF fusion construct does not have a significant impact on clinical outcomes.

On-Field Management of Suspected Spinal Cord Injury.

Acute spinal cord injuries in athletes are rare. However, on-field management of such injuries requires a well-planned approach from a team of well-trained medical staff. Athletes wearing protective gear should be handled with care; a primary survey should be conducted to rule out life-threatening injury while concomitantly immobilizing the spine. Treatment with steroids or hypothermia have not been shown to be beneficial, ultimately time to surgery provides the athlete with the best chance of a good outcome.

Updated Review: The Steroid Controversy for Management of Spinal Cord Injury.

BACKGROUND: Acute spinal cord injury (ASCI) is a devastating event that can have a profound impact on the lives of patients and their families. While no definitive medical treatment exists, the role of methylprednisolone (MP) in the management of ASCI and other spinal cord pathologies has been investigated in depth; however, its use remains contentious. While MP initially showed promise in the efficacy of ASCI treatment, more recent studies have questioned its use citing numerous systemic adverse effects. Pharmacologic treatments in this area are poorly understood due to the scarcity of knowledge surrounding the pathophysiology and heterogeneity of patients presenting with these conditions. Despite these shortcomings and due to the lack of alternative treatment options, MP is still widely used by physicians. METHODS: We review prior and current literature on the use of MP treatment for ASCI patients with a discussion of novel drug delivery systems that have demonstrated the potential to improve MP's bioavailability at the site of injury while minimizing systemic side effects. In addition, current views on the role of MP and dexamethasone in metastatic spinal cord compression and postoperative infection are reviewed. RESULTS: While some data support benefits in the use of steroids on spinal cord pathology, extensive research suggests at best limited effects and an unresolvable risk/benefit problem. CONCLUSIONS: At present, evidence regarding use of dexamethasone for MSCC is contentious, especially regarding dose regiments. Ultimately, further investigation into the use of steroids is required to determine its utility in treating patients with spinal cord pathology.

Current incidence of adjacent segment pathology following lumbar fusion versus motion-preserving procedures: a systematic review and meta-analysis of recent projections.

BACKGROUND CONTEXT: Lumbar fusion has shown to be an effective surgical management option when indicated, improving patient outcomes and functional status. However, concerns of adjacent segment pathology (ASP) due to reduced mobility at the operated segment have fostered the emergence of motion-preserving procedures (MPP). PURPOSE: To assess rates of radiographic adjacent segment degeneration (ASDeg) and symptomatic adjacent segment disease (ASDis) as well as reoperation rates due to ASP in patients who have undergone lumbar fusion compared to motion-preservation for degenerative disorders. STUDY DESIGN: Systematic Review and Meta-Analysis. METHODS: Following PRISMA guidelines, a systematic review and meta-analysis was conducted to find current (1/2012-12/2019) retrospective cohort studies and randomized controlled trials evaluating rates of ASDeg, ASDis, and reoperations due to lumbar ASP. RESULTS: A total of 1,751 patients (791 underwent fusion surgery and 960 motion-preserving procedures) in 19 publications were included in the final analysis. Overall incidence rates of ASDeg, ASDis, and reoperation rates were 27.8%, 7.6%, and 4.6%, respectively. Results showed no significant difference between the lumbar fusion versus MPP cohorts in incidence of ASDeg (36.4% vs. 19.2%, p: 0.06), ASDis (10.7% vs. 4.42%, p: 0.25), or reoperation due to ASP (7.40% vs. 1.80%, p: 0.19). Fixed-effects analysis revealed patients who underwent MPP had significantly lower odds of ASDeg (OR: 2.57, CI: 1.95, 3.35, p<.05) and reoperations (OR: 3.18, CI: 1.63, 6.21, p<.05) compared to lumbar fusion patients. CONCLUSIONS: This meta-analysis revealed no statistically significant difference in incidence of ASDeg, ASDis, or reoperations due to ASP for patients after lumbar fusion versus MPP. Weighted analysis, however, showed that MPP patients had significantly lower odds of ASDeg and reoperations due to ASP. While previous studies have established the biomechanical efficacy of MPP on cadaveric models, further high-quality studies are required to evaluate the long-term consequences of these procedures on patient-reported outcomes, postoperative complications, and associated inpatient/outpatient costs.

Demographic Analysis of Lumbar Pedicle Diameters in a Diverse Population.

STUDY DESIGN: Retrospective chart review. PURPOSE: We sought to determine the differences in pedicle diameter (PD) in the lumbar spine between various races: 'Asian,' 'Black,' 'White,' and 'Other.' These data could aid in perioperative planning during instrumented spinal fusion. OVERVIEW OF LITERATURE: Recent literature underscores the importance of understanding diverse pedicle isthmus morphology to perform successful transpedicular procedures. These studies suggest that more detailed and reliable measurements of pedicles should be undertaken. However, none of the current literature comprehensively compares average PDs between diverse racial populations with a standardized study design. METHODS: Coronal cuts of 5,060 lumbar spine pedicles were inspected to obtain their transverse outer cortical PD as measured through the isthmus at L1-L5. Data were collected and categorized on the basis of patient-reported race. We examined average PD and PD range at each level for each race. To determine the significance, we used a mixed analysis of variance and a post hoc analysis. RESULTS: The Asian cohort consistently had a significantly smaller PD at L1-L5 than Blacks or Whites (p<0.001), as did the 'Other' group compared with Blacks (p<0.001) and Whites (p=0.032). At L1-L2, the 'Other' group showed the least variability in PD. At L3-L5, the Asian population showed the smallest range, and the Black population had the largest variability in PD except at L5. There was a significant difference in PD between the various races. CONCLUSIONS: The Asian population consistently has significantly smaller pedicles in the lumbar spine than the Black or White populations. This information could prove useful for surgical planning. We suggest using preoperative computed tomography for pedicle screw templating as a safe method for pedicle screw instrumentation with the highest pullout strength given the wide range of PD in the Black population and the variability of PD between races.

Effect of using a wearable device on clinical decision-making and motor symptoms in patients with Parkinson's disease starting transdermal rotigotine patch: A pilot study.

BACKGROUND: Feedback from wearable biosensors may help assess motor function in Parkinson's disease (PD) patients and titrate medication. Kinesia 360 continuously monitors motor symptoms via wrist and ankle sensors. METHODS: PD0049 was a 12-week pilot study to investigate whether using Kinesia 360 at home could improve motor symptom management in PD patients starting transdermal dopamine agonist rotigotine. Adults with PD and insufficiently controlled motor symptoms (prescribed rotigotine) were randomized 1:1 to Control Group (CG) or Experimental Group (EG) before starting rotigotine. Motor symptoms were assessed in all patients at baseline and Week 12 (W12) using Unified PD Rating Scale (UPDRS) III and Kinesia ONE, which measures standardized motor tasks via a sensor on the index finger. Between baseline and W12, EG used Kinesia 360 at home; clinicians used the data to supplement standard care in adjusting rotigotine dosage. RESULTS: At W12, least squares mean improvements in UPDRS II (-2.1 vs 0.5, p = 0.004) and UPDRS III (-5.3 vs -1.0, p = 0.134) were clinically meaningfully greater, and mean rotigotine dosage higher (4.8 vs 3.9 mg/24 h) in EG (n = 19) vs CG (n = 20). Mean rotigotine dosage increase (+2.8 vs + 1.9 mg/24 h) and mean number of dosage changes (2.8 vs 1.8) during the study were higher in EG vs CG. Tolerability and retention rates were similar. CONCLUSION: Continuous, objective, motor symptom monitoring using a wearable biosensor as an adjunct to standard care may enhance clinical decision-making, and may improve outcomes in PD patients starting rotigotine.

Clinical feasibility of a wearable, conformable sensor patch to monitor motor symptoms in Parkinson's disease.

INTRODUCTION: Clinical assessment of motor symptoms in Parkinson's disease (PD) is subjective and may not reflect patient real-world experience. This two-part pilot study evaluated the accuracy of the NIMBLE wearable biosensor patch (containing an accelerometer and electromyography sensor) to record body movements in clinic and home environments versus clinical measurement of motor symptoms. METHODS: Patients (Hoehn & Yahr 2-3) had motor symptom fluctuations and were on a stable levodopa dose. Part 1 investigated different sensor body locations (six patients). In Part 2, 21 patients wore four sensors (chest, and most affected side of shin, forearm and back-of-hand) during a 2-day clinic- and 1-day home-based evaluation. Patients underwent Unified Parkinson's Disease Rating Scale assessments on days 1-2, and performed pre-defined motor activities at home on day 3. An algorithm estimated motor-symptom severity (predicted scores) using patch data (in-clinic); this was compared with in-clinic motor symptom assessments (observed scores). RESULTS: The overall correlation coefficient between in-clinic observed and sensor algorithm-predicted scores was 0.471 (p = 0.031). Predicted and observed scores were identical 45% of the time, with a predicted score within a ±1 range 91% of the time. Exact accuracy for each activity varied, ranging from 32% (pronation/supination) to 67% (rest-tremor-amplitude). Patients rated the patch easy-to-use and as providing valuable data for managing PD symptoms. Overall patch-adhesion success was 97.2%. The patch was safe and generally well tolerated. CONCLUSIONS: This study showed a correlation between sensor algorithm-predicted and clinician-observed motor-symptom scores. Algorithm refinement using patient populations with greater symptom-severity range may potentially improve the correlation.

Nanoporous organosilicas as preconcentration materials for the electrochemical detection of trinitrotoluene.

We describe the use of nanoporous organosilicas for rapid preconcentration and extraction of trinitrotoluene (TNT) for electrochemical analysis and demonstrate the effect of template-directed molecular imprinting on TNT adsorption. The relative effects of the benzene (BENZ)- and diethylbenzene (DEB)-bridged organic-inorganic polymers, having narrow or broad pore size distributions, respectively, on electrochemical response and desorption behavior were examined. Sample volumes of 0.5-10 mL containing 5-1000 ppb TNT in a phosphate-buffered saline buffer were preconcentrated in-line before the detector using a microcolumn containing 10 mg of imprinted BENZ or DEB. Square-wave voltammetry was used to detect the first reduction peak of TNT in an electrochemical flow cell using a carbon working electrode and a Ag/AgCl reference electrode. Imprinted BENZ released TNT faster than imprinted DEB with considerably less peak tailing and displayed enhanced sensitivity and an improvement in the limit of detection (LOD) owing to more rapid elution of TNT from that material with increasing signal amplitude. For imprinted BENZ, the slope of signal versus concentration scaled linearly with increasing preconcentration volume, and for preconcentrating 10 mL of sample, the LOD for TNT was estimated to be 5 ppb. Template-directed molecularly imprinted DEB (TDMI-DEB) was 7-fold more efficient in adsorption of TNT from aqueous contaminated soil extract than nonimprinted DEB.

Detection of organics using porphyrin embedded nanoporous organosilicas.

Molecularly imprinted polymers and silica have been studied as receptor binding site mimics for use in a wide range of separation, catalysis, and detection applications employing transduction mechanisms including conductometric, amperometric, and capacitance. Porphyrins are also well known as sensor components due to the extreme sensitivity of their spectrophotometric characteristics to changes in their immediate environment. We have developed periodic mesoporous organosilicas (PMO) which incorporate a porphyrin into the material for use as an optical indicator of target binding. This material combines the stability, selectivity, and high density of binding sites characteristic of the molecularly imprinted PMO with the sensitivity and selectivity of the porphyrin. We demonstrate binding of p-nitrophenol, p-cresol, 2,4,6-trinitrotoluene, and RDX by the porphyrin-embedded PMOs with selective adsorption of TNT over the other analytes. In addition, the binding of each of the organics by the PMO results in unique changes in the spectrophotometric characteristics of the incorporated porphyrin. These changes can be observed by visual inspection or through the use of fluorescence spectra collected in 96-well format.

Investigation of surface interactions in molecular recognition of phosphonate imprinted organosilicates and the role of water.

Surface interactions in molecular recognition of phosphonate imprinted organosilicates and the role of water have been studied. NMR and calorimetry studies have shown the changing nature of the surface water structure on silicate surfaces due to template directed molecular imprinting. Results indicate the interaction of an organophosphonate compound with the functionalized silica surfaces to be through surrounding water molecules. However, with nonfunctionalized surfaces, additional higher energy interactions were possible. Further, our results support the possible templating effect of water during the imprint process.

Benefit-risk assessment of paliperidone oral extended-release tablet versus monthly injectable for maintenance treatment of schizophrenia.

The purpose of this study was to conduct a post-hoc benefit-risk assessment of paliperidone palmitate once-monthly (PP1M) injectable versus oral paliperidone extended-release (ER) in schizophrenia maintenance treatment. The Benefit-Risk Action Team framework was used to structure the analysis based on patient-level data from two similar, double-blind, placebo-controlled relapse studies. Efficacy outcomes were relapse, psychiatric hospitalization, Clinical Global Impression-Severity scale, Personal and Social Performance (PSP) scale, and Positive and Negative Syndrome Scale (PANSS). Safety outcomes were extrapyramidal symptom-related adverse events, weight gain, prolactin-related adverse events, somnolence, orthostatic hypotension, anticholinergic use, fasting plasma glucose, and total cholesterol/high-density lipoprotein. For the first 8 weeks of maintenance treatment, most efficacy outcomes significantly favored PP1M compared with paliperidone ER. Per 1000 patients, there would be 165, 115, 85, and 53 fewer cases of PSP worsening, relapse, PANSS worsening, and hospitalizations, respectively. For the first 40 weeks, PSP worsening significantly favored PP1M (140 fewer cases). Relapse, PANSS, hospitalizations, and Clinical Global Impression-Severity scale showed a consistent pattern favoring PP1M but were not significant. Safety outcomes for both 8-week and 40-week periods demonstrated no statistically significant differences between groups. These analyses suggest a benefit-risk profile favoring PP1M over oral paliperidone ER throughout 40 weeks of treatment, particularly in early treatment.