Association of sensory phenotype with quality of life, functionality, and emotional well-being in patients suffering from neuropathic pain.

ABSTRACT: Neuropathic pain highly affects quality of life, well-being, and function. It has recently been shown based on cluster analysis studies that most patients with neuropathic pain may be categorized into 1 of 3 sensory phenotypes: sensory loss, mechanical hyperalgesia, and thermal hyperalgesia. If these phenotypes reflect underlying pathophysiological mechanisms, they may be more relevant for patient management than underlying neurological diagnosis or pain intensity. The aim of this study was thus to examine the impact of these sensory phenotypes on mental health, functionality, and quality of life. Data of 433 patients from the IMI/EuroPain network database were analyzed, and results of HADS-D/A, Pain Catastrophizing Scale, Euro Quality of Life 5D/-VAS, Brief Pain Inventory, and Graded Chronic Pain Scale between the sensory phenotypes were compared using multiple regression analysis. There was no difference in chronic pain grade, pain intensity, depression, or anxiety scores between phenotypes. Pain interference (Brief Pain Inventory) was higher (P = 0.002); self-reported health state lower (Euro Quality of Life 5D VAS, P = 0.02); and problems regarding mobility (P = 0.008), usual activities (P = 0.004), and self-care (P = 0.039) more prominent (EQ5-D) in the sensory loss compared with the thermal hyperalgesia phenotype. Patients with sensory loss also showed higher pain catastrophizing scores (P = 0.006 and 0.022, respectively) compared with the 2 other groups. Sensory phenotype is associated with the impact of neuropathic pain conditions on well-being, daily functionality, and quality of life but is less associated with pain intensity. These results suggest that the somatosensory phenotype should be considered for personalized pain management.

Improving Groundwater Model Calibration with Repeat Microgravity Measurements.

Groundwater-flow models depend on hydraulic head and flux observations for evaluation and calibration. A different type of observation-change in storage measured using repeat microgravity-can also be used for parameter estimation by simulating the expected change in gravity from a groundwater model and including the observation misfit in the objective function. The method is demonstrated using new software linked to MODFLOW input and output files and field data from the vicinity of the All American Canal in southeast California, USA. Over a 10-year period following lining of the previously highly permeable canal with concrete, gravity decreased by over 100 µGal (equivalent to about 2.5 m of free-standing water) at some locations as seepage decreased and the remnant groundwater mound dissipated into the aquifer or was removed by groundwater pumping. Simulated gravity from a MODFLOW model closely matched observations, and repeat microgravity data proved useful for constraining both hydraulic conductivity and specific yield estimates. Specific yield estimated using the infinite-horizontal slab approximation agreed well with model-derived values, and the departure from the linear, flat-water-table approximation was small, less than 2%, despite relatively large and dynamic water-table slope. First-order second-moment parameter uncertainty analysis shows reduction in uncertainty for all hydraulic conductivity and specific yield parameter estimates with the addition of repeat microgravity data, as compared to drawdown data alone.

Motivation to Lead as Mediator of Relations Between the Dark Triad, Big Five, and Leadership Intention.

This study seeks to enhance the distal-proximal modeling of personality trait-leader emergence relationships by (1) distinguishing between the motivation to lead (i.e., the reasons why a person seeks leadership roles) and leadership intention (i.e., one's expressed desire to claim a leadership role) and by (2) examining how the Dark Triad traits add to the Big Five personality factors in predicting three motivation to lead factors and leadership intentions. Using personality and careers aspiration data collected from 750 university students, we found that affective-identity and social-normative motivation to lead mediate the effects of distal traits on intentions. In contrast, non-calculative motivation to lead does not contribute to leadership intentions, which has important implications for organizations seeking selfless leaders. Narcissism explains variance in leadership intentions over and above that explained by extraversion; this contrasts with the studies of leader emergence, where the effect of narcissism disappears once extraversion is controlled. Overall, our findings validate the three-factor conceptualization of motivation to lead and illuminate the roles of both bright and dark personality factors in understanding individual desire to attain leadership roles.

The impact of sub specialization within functional neurosurgery on patient outcomes in a comprehensive epilepsy center.

BACKGROUND: One in three patients with epilepsy are medication-refractory and may benefit from investigations and operative treatment at a comprehensive epilepsy center. However, while these centers have capabilities for advanced seizure monitoring and surgical intervention, they are not required to have a functional neurosurgeon who is primarily focused in epilepsy surgery. Therefore, the objective of this study is to determine the impact of having a sub-specialized, epilepsy-focused functional neurosurgeon on patient outcomes. METHODS: We conducted a retrospective chart review for all patients who underwent surgical intervention for medically refractory epilepsy at a Level 4 comprehensive Epilepsy Center from 2008 through 2019. Data was divided into two groups: group 1 comprised patients who had surgery before the hiring of a dedicated epilepsy-focused functional neurosurgeon in 2016, and group 2 was afterwards. We compared surgical procedures, significant complications, and seizure outcomes. RESULTS: A total of 101 patients underwent 105 operations (52 in group 1 and 53 in group 2), not including intracranial EEG insertion. Compared to group 1, group 2 had more surgeries performed per year (15.1 vs. 6.5), and a significantly lower Engel score at last follow-up (1.78 vs. 2.57; p < 0.001). There was no difference in percentage of cases undergoing iEEG, and no difference in complication rates. CONCLUSIONS: In this series, the hiring of a sub-specialized functional neurosurgeon dedicated to epilepsy surgery in a comprehensive epilepsy center was associated with an increase in surgical volume and improved seizure outcomes.

Continuous Electroencephalographic Training for Neuroscience Intensive Care Unit Nurses: A Feasibility Study.

BACKGROUND: Use of continuous electroencephalographic (cEEG) monitoring has more than doubled at our institution for the last 4 years. Although intensive care unit cEEG is reviewed remotely by board-certified epileptologists every 4 to 6 hours, there are inherent delays between occurrence, recognition, and treatment of epileptiform activity. Neuroscience intensive care unit (NSICU) nurses are uniquely positioned to monitor cEEG in real time yet do not receive formal training. The purpose of this study was to evaluate the effectiveness of an education program to teach nurses to monitor cEEG, identify a burst suppression pattern, and measure the duration of suppression. METHODS: We performed a retrospective analysis of pretest and posttest data. All NSICU nurses (40) were invited to complete the pretest (PT-0), with 25 participating. Learning style/preference, demographics, comfort with cEEG, and knowledge of EEG fundamentals were assessed. A convenience cohort of NSICU nurses (13) were selected to undergo EEG training. Posttests evaluating EEG fundamental knowledge were completed immediately after training (PT-1), at 3 months (PT-3), and at 6 months (PT-6). The cohort also completed a burst suppression module after the training, which assessed ability to quantify the duration of suppression. RESULTS: Mean cohort test scores significantly improved after the training (P < .001). All nurses showed improvement in test scores, and 76.9% passed PT-1 (a score of 80% or higher). Reported mean comfort level with EEG also significantly improved after the training (P = .001). There was no significant difference between mean cohort scores between PT-1, PT-3, and PT-6 (all 88.6%; P = 1.000). Mean cohort score from the bust suppression module was 73%, with test scores ranging from 31% to 93%. CONCLUSIONS: NSICU nurses can be taught fundamentals of cEEG, to identify a burst suppression pattern, and to quantify the duration of suppression. Further research is needed to determine whether this knowledge can be translated into clinical competency and affect patient care.

Superior accuracy and precision of SEEG electrode insertion with frame-based vs. frameless stereotaxy methods.

BACKGROUND: Stereotactic electroencephalography (SEEG) has largely become the preferred method for intracranial seizure localization in epileptic patients due to its low morbidity and minimally invasive approach. While robotic placement is gaining popularity, many centers continue to use manual frame-based and frameless methods for electrode insertion. However, it is unclear how these methods compare in regard to accuracy, precision, and safety. Here, we aim to compare frame-based insertion using a CRW frame (Integra®) and frameless insertion using the StealthStation™ S7 (Medtronic®) navigation system for common temporal SEEG targets. METHODS: We retrospectively examined electrode targets in SEEG patients that were implanted with either frame-based or frameless methods at a level 4 epilepsy center. We focused on two commonly used targets: amygdala and hippocampal head. Stealth station software was used to merge pre-operative MR with post-operative CT images for each patient, and coordinates for each electrode tip were calculated in relation to the midcommissural point. These were compared to predetermined ideal coordinates in regard to error and directional bias. RESULTS: A total of 81 SEEG electrodes were identified in 23 patients (40 amygdala and 41 hippocampal head). Eight of 45 electrodes (18%) placed with the frameless technique and 0 of 36 electrodes (0%) placed with the frame-based technique missed their target and were not clinically useful. The average Euclidean distance comparing actual to ideal electrode tip coordinates for frameless vs. frame-based techniques was 11.0 mm vs. 7.1 mm (p < 0.001) for the amygdala and 12.4 mm vs. 8.5 mm (p < 0.001) for the hippocampal head, respectively. There were no hemorrhages or clinical complications in either group. CONCLUSIONS: Based on this series, frame-based SEEG insertion is significantly more accurate and precise and results in more clinically useful electrode contacts, compared to frameless insertion using a navigation guidance system. This has important implications for centers not currently using robotic insertion.

From adagio to allegretto: The changing tempo of theta frequencies in epilepsy and its relation to interneuron function.

Despite decades of research, our understanding of epilepsy, including how seizures are generated and propagate, is incomplete. However, there is growing recognition that epilepsy is more than just the occurrence of seizures, with patients often experiencing comorbid deficits in cognition that are poorly understood. In addition, the available therapies for treatment of epilepsy, from pharmaceutical treatment to surgical resection and seizure prevention devices, often exacerbate deficits in cognitive function. In this review, we discuss the hypothesis that seizure generation and cognitive deficits have a similar pathological source characterized by, but not limited to, deficits in theta oscillations and their influence on interneurons. We present a new framework that describes oscillatory states in epilepsy as alternating between hyper- and hypo-synchrony rather than solely the spontaneous transition to hyper-excitability characterized by the seizures. This framework suggests that as neural oscillations, specifically in the theta range, vary their tempo from a slowed almost adagio tempo during interictal periods to faster, more rhythmic allegretto tempo preictally, they impact the function of interneurons, modulating their ability to control seizures and their role in cognitive processing. This slow wave oscillatory framework may help explain why current therapies that work to reduce hyper-excitability do not completely eliminate seizures and often lead to exacerbated cognitive deficits.

Outcomes of Kahook Dual Blade Goniotomy with and without Phacoemulsification Cataract Extraction.

PURPOSE: To determine the effectiveness and safety of Kahook Dual Blade (KDB) goniotomy in reducing intraocular pressure (IOP) and medication need in glaucoma patients when combined with phacoemulsification or as a standalone procedure. DESIGN: Retrospective study. PARTICIPANTS: A total of 197 eyes from 143 patients were reviewed. METHODS: Thirty-two eyes underwent KDB goniotomy alone and 165 eyes underwent KDB goniotomy combined with phacoemulsification cataract surgery (phaco-KDB). MAIN OUTCOME MEASURES: Surgical success, defined as IOP reduction of at least 20% from baseline at 12 months, and/or reduction of at least 1 glaucoma medication. RESULTS: At 12 months, the success rate was 71.8% for the phaco-KDB group and 68.8% for the KDB-alone group. In the phaco-KDB group at 12 months (n = 124), mean IOP was significantly reduced from 16.7 (standard error [SE] 0.4) mmHg on 1.9 (SE 0.1) medications to 13.8 (SE 0.4) mmHg on 1.5 (SE 0.1) medications. In the KDB-alone group at 12 months (n = 16), mean IOP was significantly reduced from 20.4 (SE 1.3) mmHg on 3.1 (SE 0.2) medications to 14.1 (SE 0.9) mmHg on 2.3 (SE 0.4) medications. The most common complications were transient hyphema (17.3% at day 1) and IOP spike >10 mmHg from baseline at 1 week (10.2%). LogMAR visual acuity at 12 months was unchanged from baseline in the KDB-alone group (0.218 [SE 0.07] and 0.306 [SE 0.09], respectively, P = 0.244) and significantly improved in the phaco-KDB group (0.184 [SE 0.02] and 0.340 [SE 0.03], P < 0.001). CONCLUSIONS: Goniotomy with the KDB has a favorable safety profile and is an effective procedure at reducing IOP and medication burden as a standalone procedure or combined with phacoemulsification.

The effect of amniotic membrane grafting on healing and wound strength after strabismus surgery in a rabbit model.

BACKGROUND: Amniotic membrane grafts (AMGs) are used, with mixed results, as a platform for ocular healing and to reduce pathologic scarring. This study evaluated wound tensile strength and histopathologic changes after strabismus surgery with AMGs in 20 New Zealand white rabbits. METHODS: All subjects underwent 4 mm inferior rectus hang-back recessions to both eyes. The right eyes served as controls. Ten left eyes (group 1) received processed dehydrated amniotic membrane allografts (Ambiodry2, IOP Inc, Costa Mesa, CA) and ten left eyes (group 2) received cryopreserved human amniotic membrane allografts (AmnioGraft, Bio-Tissue, Miami, FL) between the sclera and muscle insertion and between the muscle and repositioned conjunctiva. At postoperative month 1, tensile strengths of the muscle-globe and conjunctiva-globe attachments were measured, and histopathologic analysis of each eye was performed. RESULTS: In group 1 the mean tensile strength of the muscle-globe attachments was 441.4 ± 274.4 g; of the conjunctiva-globe attachments, 640.3 ± 266.4 g. In the control eyes, the comparable values were 365.8 ± 199.8 g and 595.2 ± 315.3 g, respectively (P = 0.19, P = 0.13). In group 2 the mean tensile strengths were 456 ± 297.5 g and 608.2 ± 306.7 g, compared with control values of 352.7 ± 114.8 g and 583.8 ± 347.1 g (P = 0.43, P = 0.45). CONCLUSIONS: There was no significant change in tensile strength of the muscle insertion using AMGs. In a rabbit model, AMGs do not reduce inflammation or improve scar formation 1 month after strabismus surgery.

Who Wants to Be an Intrapreneur? Relations between Employees' Entrepreneurial, Professional, and Leadership Career Motivations and Intrapreneurial Motivation in Organizations.

This paper reports an empirical study conducted to examine the relationship between employees' Entrepreneurial, Professional, and Leadership (EPL) career motivations and their intrapreneurial motivation. Using data collected from 425 working adults in the research/innovation and healthcare settings, we develop a self-report measure of employee intrapreneurial motivation. We also adapt an existing self-report measure of E, P, and L career motivations (previously developed and used with university students) for use with working adult organizational employees. Confirmatory factor analysis indicate that E, P, and L motivations and intrapreneurial motivation can be measured independently and reliably, while regression analyses show that the employees' E, P, and L motivations all contribute to explaining variance in their intrapreneurial motivation. Individuals with high E, P, and L motivational profiles are also found to have the highest intrapreneurial motivation scores, while those low on E, P, and L motivations have the least intrapreneurial motivation. Our findings suggest that the potential for intrapreneurship is not unique to only entrepreneurial employees. Instead, one can find intrapreneurs among employees with strong leadership and professional motivations as well. We discuss the findings in the context of generating more research to address the challenges of talent management in the 21st century knowledge economies where there is greater career mobility and boundarylessness in the workforce.

Potentially high-risk cardiac arrhythmias with focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures are associated with the duration of periictal hypoxemia.

OBJECTIVE: To investigate potentially high-risk cardiac arrhythmias (PHAs) following focal to bilateral tonic-clonic seizures (FBTCSs) and generalized tonic-clonic seizures (GTCSs) and to study the association of PHAs with seizure characteristics and the severity of associated ictal respiratory dysfunction. METHODS: Electrocardiographic (EKG) and pulse oximetry (SpO2 ) data were recorded concurrently with video-electroencephalographic telemetry in the epilepsy monitoring unit (EMU). One minute of preictal EKG, the ictal EKG, and 2 min of ictal/postictal data were reviewed for each seizure. Nonsustained ventricular tachycardia, bradyarrhythmia, and/or sinus pauses were considered as PHAs. FBTCSs/GTCSs with PHAs were compared to those that had only ictal sinus tachycardia. RESULTS: Data from 69 patients with 182 FBTCSs/GTCSs with usable SpO2 and EKG recordings were available. There were 10 FBTCSs/GTCSs in 10 patients with a PHA. The presence of PHAs was not associated with seizure duration or SpO2 nadir. FBTCSs/GTCSs with a PHA were significantly associated with the duration of oxygen desaturation < 90% when compared with FBTCSs/GTCSs with only sinus tachycardia (Mann-Whitney, p = 0.042). Desaturation duration of <100 s was not significantly associated with occurrence of PHAs (p = 0.110) when compared with seizures that had only sinus tachycardia. The odds ratio for occurrence of PHA was 7.86 for desaturation durations ≥ 125 s versus desaturations < 125 s (p = 0.005). The odds ratio increased to 13.09 for desaturation durations ≥ 150 s (p < 0.001). Preictal and ictal/postictal arrhythmias occurred with focal seizures that did not progress to FBTCSs. Four patients with focal seizures had ictal/postictal PHAs without preictal PHAs. Two of these patients had evidence for prior cardiac disturbance. SIGNIFICANCE: PHAs following a single FBTCS/GTCS in the EMU are significantly associated with the duration of ictal/postictal hypoxemia. It is possible that FBTCS/GTCS-associated hypoxemia may trigger fatal cardiac arrhythmias in a subset of susceptible patients dying of sudden unexpected death in epilepsy.

Broad spectrum efficacy with LY2969822, an oral prodrug of metabotropic glutamate 2/3 receptor agonist LY2934747, in rodent pain models.

BACKGROUND AND PURPOSE: A body of evidence suggests activation of metabotropic glutamate 2/3 (mGlu2/3 ) receptors would be an effective analgesic in chronic pain conditions. Thus, the analgesic properties of a novel mGlu2/3 receptor agonist prodrug were investigated. EXPERIMENTAL APPROACH: After oral absorption, the prodrug LY2969822 rapidly converts to the brain penetrant, potent and subtype-selective mGlu2/3 receptor agonist LY2934747. Behavioural assessments of allodynia, hyperalgesia and nocifensive behaviours were determined in preclinical pain models after administration of LY2969822 0.3-10 mg·kg-1 . In addition, the ability of i.v. LY2934747 to modulate dorsal horn spinal cord wide dynamic range (WDR) neurons in spinal nerve ligated (SNL) rats was assessed. KEY RESULTS: Following treatment with LY2934747, the spontaneous activity and electrically-evoked wind-up of WDR neurons in rats that had undergone spinal nerve ligation and developed mechanical allodynia were suppressed. In a model of sensitization, orally administered LY2969822 prevented the nociceptive behaviours induced by an intraplantar injection of formalin. The on-target nature of this effect was confirmed by blockade with an mGlu2/3 receptor antagonist. LY2969822 prevented capsaicin-induced tactile hypersensitivity, reversed the SNL-induced tactile hypersensitivity and reversed complete Freund's adjuvant - induced mechanical hyperalgesia. The mGlu2/3 receptor agonist prodrug demonstrated efficacy in visceral pain models, including a colorectal distension model and partially prevented the nocifensive behaviours in the mouse acetic acid writhing model. CONCLUSIONS AND IMPLICATIONS: Following oral administration of the prodrug LY2969822, the mGlu2/3 receptor agonist LY2934747 was formed and this attenuated pain behaviours across a broad range of preclinical pain models.

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles.

Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.

Counseling by epileptologists affects contraceptive choices of women with epilepsy.

INTRODUCTION: There are several important interactions between antiepileptic drugs (AEDs) and hormonal contraception that need to be carefully considered by women with epilepsy (WWE) and their practitioners. Many AEDs induce hepatic enzymes and decrease the efficacy of hormonal contraception. In addition, estrogen-containing hormonal contraception can increase the metabolism of lamotrigine, the most commonly prescribed AED in women of childbearing age. The intrauterine device (IUD) is a highly effective form of reversible contraception without AED drug interactions that is considered by many to be the contraceptive of choice for WWE. Women with epilepsy not planning pregnancy require effective contraceptive counseling that should include discussion of an IUD. There are no guidelines, however, on who should deliver these recommendations. The objective of this study was to explore the hypothesis that contraceptive counseling by a neurologist can influence the contraceptive choices of WWE. In particular, we explored the relationship between contraceptive counseling in the epilepsy clinic and the likelihood that patients would obtain an IUD. METHODS: We conducted a retrospective chart review of female patients age 18-45 seen at our institution for an initial visit between 2010 and 2014 to ascertain the type of contraceptive counseling each patient received as well as AED use and contraceptive methods. Patients who were pregnant or planning pregnancy at the first visit were excluded from further analyses as were patients with surgical sterilization. We also examined a subgroup of 95 patients with at least 4 follow-up visits to evaluate the efficacy of epileptologists' counseling. Specifically, we looked at the likelihood a patient obtained an IUD based on the type of counseling she had received. Fisher exact tests assessed associations between counseling type and whether patients had obtained an IUD. RESULTS: Three hundred and ninety-seven women met criteria for inclusion. Only 35% of female patients were counseled about contraception at the first visit. If women were not counseled at the first visit, they were unlikely to be counseled at subsequent visits; only 37% had ever received counseling by their fourth visit. Of the 95 patients who completed 4 visits, 28.4% were counseled about an IUD as an optimal contraceptive choice, 38.9% were generally counseled about contraceptive interactions, and 32.6% were not counseled about contraception. Women with epilepsy who received IUD-specific counseling were significantly more likely to switch to an IUD (44.4%) compared with women who received no contraceptive counseling (6.5%; p=0.0009). Women with epilepsy who received IUD-specific counseling also tended to switch to an IUD more often than those women receiving general counseling about AEDs and contraceptive interactions (18.9%; p=0.027). There was no significant difference in the likelihood of acquiring an IUD between the general counseling and no counseling groups. CONCLUSIONS: Contraceptive counseling by epileptologists and specific mention of an IUD is significantly associated with patient selection of an IUD as a contraceptive method. This suggests that neurologists can play an important role in patients' contraceptive choices.

Outcomes after combined phacoemulsification and trabecular microbypass stent implantation in controlled open-angle glaucoma.

PURPOSE: To study the effect of combined phacoemulsification cataract surgery and iStent (trabecular microbypass stent) implantation on intraocular pressure (IOP) and medication use in open-angle glaucoma (OAG) patients with a low mean preoperative IOP. SETTING: University of Colorado Health Eye Center, Aurora, Colorado, USA. DESIGN: Retrospective case series. METHODS: Treatment outcomes analyzed included IOP, medication use, and corrected distance visual acuity (CDVA). Treatment success was defined as a 20% or more IOP reduction or discontinuation of at least 1 medication. RESULTS: Sixty-four eyes of 45 patients were included in the analysis. At 1 year, the mean IOP was significantly reduced from 14.7 ± 3.2 mm Hg (SD) to 13.2 ± 2.8 mm Hg (P < .01) and the mean medication use decreased from 1.81 ± 1.13 to 1.41 ± 1.48 (P = .0001). The estimated IOP reduction at 1, 3, 6, and 12 months was 3.5% (P = .23), 7.9% (P = .04), 9.7% (P = .01), and 12.2% (P = .002), respectively. Treatment success at 1 year was achieved in 76.1% of patients, and 41% of patients were medication free at 1 year. The CDVA was significantly improved from 0.4 ± 0.38 logMAR at baseline to 0.17 ± 0.35 at 1 year (P < .0001). CONCLUSIONS: Combined cataract surgery and trabecular microbypass stent implantation was statistically effective in reducing IOP and/or medication burden in OAG patients with a low preoperative IOP. During the informed surgical consent process, the physician and patient should consider the clinical benefit of modest IOP lowering and/or a decrease in medication use. FINANCIAL DISCLOSURE: Drs. Seibold, SooHoo, Pantcheva, and Kahook have received grant support from Glaukos Corp. No other author has a financial or proprietary interest in any material or method mentioned.

Effect of human milk as a treatment for dry eye syndrome in a mouse model.

PURPOSE: Dry eye syndrome (DES) affects millions of people worldwide. Homeopathic remedies to treat a wide variety of ocular diseases have previously been documented in the literature, but little systematic work has been performed to validate the remedies' efficacy using accepted laboratory models of disease. The purpose of this study was to evaluate the efficacy of human milk and nopal cactus (prickly pear), two widely used homeopathic remedies, as agents to reduce pathological markers of DES. METHODS: The previously described benzalkonium chloride (BAK) dry eye mouse model was used to study the efficacy of human milk and nopal cactus (prickly pear). BAK (0.2%) was applied to the mouse ocular surface twice daily to induce dry eye pathology. Fluorescein staining was used to verify that the animals had characteristic signs of DES. After induction of DES, the animals were treated with human milk (whole and fat-reduced), nopal, nopal extract derivatives, or cyclosporine four times daily for 7 days. Punctate staining and preservation of corneal epithelial thickness, measured histologically at the end of treatment, were used as indices of therapeutic efficacy. RESULTS: Treatment with BAK reduced the mean corneal epithelial thickness from 36.77±0.64 µm in the control mice to 21.29±3.2 µm. Reduction in corneal epithelial thickness was largely prevented by administration of whole milk (33.2±2.5 µm) or fat-reduced milk (36.1±1.58 µm), outcomes that were similar to treatment with cyclosporine (38.52±2.47 µm), a standard in current dry eye therapy. In contrast, crude or filtered nopal extracts were ineffective at preventing BAK-induced loss of corneal epithelial thickness (24.76±1.78 µm and 27.99±2.75 µm, respectively), as were solvents used in the extraction of nopal materials (26.53±1.46 µm for ethyl acetate, 21.59±5.87 µm for methanol). Epithelial damage, as reflected in the punctate scores, decreased over 4 days of treatment with whole and fat-reduced milk but continued to increase in eyes treated with nopal-derived materials. CONCLUSIONS: Whole and fat-reduced human milk showed promising effects in the prevention of BAK-induced loss of corneal epithelial thickness and epithelial damage in this mouse model. Further studies are required to determine whether human milk may be safely used to treat dry eye in patients.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.

Hedonic and motivational responses to food reward are unchanged in rats with neuropathic pain.

Rewards influence responses to acute painful stimuli, but the relationship of chronic pain to hedonic or motivational aspects of reward is not well understood. We independently evaluated hedonic qualities of sweet or bitter tastants and motivation to seek food reward in rats with experimental neuropathic pain induced by L5/6 spinal nerve ligation. Hedonic response was measured by implantation of intraoral catheters to allow passive delivery of liquid solutions, and "liking/disliking" responses were scored according to a facial reactivity scale. Spinal nerve ligation rats did not differ from controls in either "liking" or "disliking" reactions to intraoral sucrose or quinine, respectively, at postsurgery day 21, suggesting no differences in perceived hedonic value of sweet or bitter tastants. To assess possible motivational deficits during acute and chronic pain, we used fixed- and progressive-ratio response paradigms of sucrose pellet presentation in rats with transient inflammatory or chronic neuropathic pain. Assessment of response acquisition and break points under the progressive ratio schedule revealed no differences between sham and spinal nerve ligation rats for up to 120 days after injury. However, rats with inflammation showed decrements in lever pressing and break points on days 1 and 2 after complete Freund adjuvant injection that normalized by day 4, consistent with transient ongoing pain. Thus, although acute ongoing inflammatory pain may transiently reduce reward motivation, we did not detect influences of chronic neuropathic pain on hedonic or motivational responses to food rewards. Adaptations that allow normal reward responding to food regardless of chronic pain may be of evolutionary benefit to promote survival.

Selective Laser Trabeculoplasty: An Update.

Selective laser trabeculoplasty (SLT) is an effective treatment option for the reduction of intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. The mechanism by which SLT lowers IOP is not completely understood and is likely multifactorial. Published studies indicate that SLT is at least as effective as argon laser trabeculoplasty or medications at lowering IOP in many forms of glaucoma. In addition to IOP reduction, SLT may decrease IOP fluctuation and can be successfully used as primary or adjunctive therapy for the management of both early and advanced glaucoma. However, SLT may not be effective in certain forms of glaucoma, and the IOP-lowering effect seems to wane with time. High pretreatment IOP is the strongest predictor of treatment success, even in patients with normal-tension glaucoma. Repeatability of SLT has been controversial, but recent evidence suggests that it can be successfully repeated to achieve additional or recurrent IOP reduction, even in eyes that only had a modest response to initial treatment. Adverse events are uncommon after SLT, and the most common complications such as discomfort and inflammation are typically mild and transient. Further investigation is required to determine the optimal treatment parameters for SLT treatment. Limited evidence suggests that SLT is cost-effective as primary therapy for patients with glaucoma.