Evaluation of Real and Perceived Risk to Health Care Workers Caring for Patients With the Omicron Variant of the SARS-CoV-2 Virus in Surgery and Obstetrics.

OBJECTIVES: The Omicron variant of the SARS-CoV-2 virus is described as more contagious than previous variants. We sought to assess risk to health care workers (HCWs) caring for patients with COVID-19 in surgical/obstetrical settings, and the perception of risk among this group. METHODS: From January to April 2022, reverse transcription polymerase chain reaction was used to detect the presence of SARS-CoV-2 viral ribonucleic acid in patient, environmental (floor, equipment, passive air) samples, and HCWs' masks (inside surface) during urgent surgery or obstetrical delivery for patients with SARS-CoV-2 infection. The primary outcome was the proportion of HCWs' masks testing positive. Results were compared with our previous cross-sectional study involving obstetrical/surgical patients with earlier variants (2020-2021). HCWs completed a risk perception electronic questionnaire. RESULTS: Eleven patients were included: 3 vaginal births and 8 surgeries. In total, 5/108 samples (5%) tested positive (SARS-CoV-2 Omicron) viral ribonucleic acid: 2/5 endotracheal tubes, 1/22 floor samples, 1/4 patient masks, and 1 nasal probe. No samples from the HCWs' masks (0/35), surgical equipment (0/10), and air (0/11) tested positive. No significant differences were found between the Omicron and 2020/21 patient groups' positivity rates (Mann-Whitney U test, P = 0.838) or the level of viral load from the nasopharyngeal swabs (P = 0.405). Nurses had a higher risk perception than physicians (P = 0.038). CONCLUSION: No significant difference in contamination rates was found between SARS-CoV-2 Omicron BA.1 and previous variants in surgical/obstetrical settings. This is reassuring as no HCW mask was positive and no HCW tested positive for COVID-19 post-exposure.

Quality of life issues in patients with bone metastases: A systematic review.

INTRODUCTION: Bones are frequent sites of metastatic disease, observed in 30-75% of advanced cancer patients. Quality of life (QoL) is an important endpoint in studies evaluating the treatments of bone metastases (BM), and many patient-reported outcome tools are available. The primary objective of this systematic review was to compile a list of QoL issues relevant to BM and its interventions. The secondary objective was to identify common tools used to assess QoL in patients with BM, and the QoL issues they fail to address. METHODS: A search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases between 1946 and 27 January 2023 with the keywords "bone metastases", "quality of life", and "patient reported outcomes". Specific QoL issues in original research studies and the QoL tools used were extracted. RESULTS: The review identified the QoL issues most prevalent to BM in the literature. Physical and functional issues observed in patients included pain, interference with ambulation and daily activities, and fatigue. Psychological symptoms, such as helplessness, depression, and anxiety were also common. These issues interfered with patients' relationships and social activities. Items not mentioned in existing QoL tools were related to newer treatments of BM, such as pain flare, flu-like symptoms, and jaw pain due to osteonecrosis. CONCLUSIONS: This systematic review highlights that QoL issues for patients with BM have expanded over time due to advances in BM-directed treatments. If they are relevant, additional treatment-related QoL issues identified need to be validated prospectively by patients and added to current assessment tools.

Pulsed Radiofrequency of Pudendal Nerve for Treatment in Patients with Pudendal Neuralgia. A Case Series with Long-Term Follow-Up.

Pudendal neuralgia (PN) is an impairing neuropathic disorder, affecting both men and women, involving a severe burning and sharp pain along the course of the pudendal nerve. Treatment is often insufficient, and options are limited. Pulsed radiofrequency (PRF) is a technique which might be useful in therapy. This case series aims to determine the effectiveness of PRF in patients with PN in the context of evaluation of care. Between 2010 and 2016, all female patients of University Medical Center Utrecht diagnosed with PN who experience insufficient pain relief after common treatment were offered PRF. Patient Global Impression of Improvement (PGI-I) scores were assessed at 3-month follow-up and at long-term follow-up (median 4 years). PGI-I scores were recorded to evaluate our quality of care. Twenty patients with PN consented to undergo PRF. We lost one patient in follow-up. Seventy-nine percent of the patients described their condition as "(very) much better" at 3-month follow-up. At long-term follow-up, 89% of the patients described their condition as "(very) much better." No serious side effects were observed. In conclusion, PRF is a successful treatment option in patients not responding to standard treatment options, including pudendal nerve blocks. PRF of the pudendal nerve can be used for PN to provide relief in patients' chronic pelvic pain.

Advancing spinal fellowship training: an international multi-centre educational perspective.

PURPOSE: The purpose of this article is to review the importance of contemporary spine surgery fellowships and educational strategies to assist with fellowship design and delivery. METHODS: Spine surgery fellowship includes trainees from orthopaedic and neurosurgical backgrounds and is increasingly indicated for individuals wishing to pursue spine surgery as a career, recognizing how spinal surgery evolved significantly in scope and complexity. We combine expert opinion with a review of the literature and international experience to expound spine fellowship training. RESULTS: Contemporary learning techniques include boot camps at the start of fellowship which may reinforce previous clinical learning and help prepare fellows for their new clinical roles. There is good evidence that surgical specialty training boot camps improve clinical skills, knowledge and trainee confidence prior to embarking upon new clinical roles with increasing levels of responsibility. Furthermore, as simulation techniques and technologies take on an increasing role in medical and surgical training, we found evidence that trainees' operative skills and knowledge can improve with simulated operations, even if just carried out briefly. Finally, we found evidence to suggest a role for establishing competence-based objectives for training in specific operative and technical procedures. Competence-based objectives are helpful for trainees and trainers to highlight gaps in a trainee's skill set that may then be addressed during training. CONCLUSIONS: Spinal fellowships may benefit from certain contemporary strategies that assist design and delivery of training in a safe environment. Interpersonal factors that promote healthy teamwork may contribute to an environment conducive to learning. These slides can be retrieved under Electronic Supplementary Material.

Cost-effectiveness of vaccination of immunocompetent older adults against herpes zoster in the Netherlands: a comparison between the adjuvanted subunit and live-attenuated vaccines.

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective. RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

EUS-guided celiac ganglia neurolysis: a clinical and human cadaver study (with video).

BACKGROUND AND AIMS: There is little evidence that structures targeted during EUS-guided celiac ganglia neurolysis (EUS-CGN) are celiac ganglia and that selective ethanol injection into ganglia is feasible. We aimed to visualize celiac ganglia, confirm that these structures are ganglia, and visualize ethanol spread after EUS-CGN and EUS-guided celiac plexus neurolysis (EUS-CPN). METHODS: First, celiac ganglia were sought during 97 consecutive EUS procedures. Second, ganglia were identified in a prosected human cadaver by placing a linear echoendoscope next to the celiac trunk and removing the underlying tissue for histology. Finally, various EUS-CGN and EUS-CPN techniques were performed in human cadavers; EUS-CGN was performed with 1 mL ethanol in 1 ganglion, 1 mL per ganglion (both low volume), and 4 mL per ganglion (high volume). EUS-CPN was performed with a central (20 mL) and a bilateral (2*10 mL) approach. Transverse sections (75 µm) were obtained and photographed to allow visualization of the spread of ethanol. RESULTS: A total of 204 ganglia were detected in 83 patients. Mean (± standard deviation) size of the long axis was 8.1 mm (± 7.4 mm). Histology of the removed region in the cadaver showed only nerve cell bodies. After low-volume EUS-CGN in cadavers, ethanol spread well beyond the targeted ganglion. After high-volume EUS-CGN in cadavers, a larger ethanol spread was seen, which also reached unidentified ganglia; the spread was comparable to the spread after EUS-CPN. CONCLUSIONS: Specific EUS-CGN is not feasible because ethanol spreads well beyond the targeted ganglion. Unidentified celiac ganglia are better reached with high-volume EUS-CGN, and this would likely result in a more thorough neurolysis. High-volume EUS-CGN should be preferred to low-volume EUS-CGN.

Pain, Itch, Quality of Life, and Costs after Herpes Zoster.

BACKGROUND: Herpes zoster (HZ) and postherpetic neuralgia are known to have a profound effect on the patient's quality of life, but the incidence and severity of itch and its relation with pain and quality of life in the long term are still relatively unknown. OBJECTIVE: The aim of this study was to measure the presence and severity of pain and itch and impact on quality of life in patients over 50 years old with HZ. METHODS: We enrolled 661 patients with HZ in this 12-month observational study. Patient data were collected via a web-based questionnaire. Outcomes were pain, itch, burden of illness, impact on patient's daily life, impact on quality of life, and healthcare costs. RESULTS: At inclusion, 94% of patients reported any pain, 74.3% significant pain, and 26% severe pain. After 3 months, 18.8% of patients suffered from postherpetic neuralgia. At inclusion, 70.8% of patients had any itch, 39.2% significant itch, and 7.3% severe itch. The occurrence of pain increases costs and has a high impact on the quality of life, lowering EQ-5D scores by an average of 18%. In contrast, itch has little effect on the quality of life. CONCLUSIONS: Pain and itch are highly prevalent months after HZ. Pain caused by HZ has a large impact on quality of life, burden of illness, impact on daily life, and health care costs for these patients. The impact of itch on quality of life is relatively small.

Versican 3'-untranslated region (3'UTR) promotes dermal wound repair and fibroblast migration by regulating miRNA activity.

Versican is an extracellular chondroitin sulfate proteoglycan which functions as a structural molecule but can also regulate a variety of cellular activities. This study was designed to explore the roles of versican in the process of dermal wound repair. To elevate levels of versican, we ectopically expressed the versican 3'-untranslated region (3'UTR) as a competitive endogenous RNA to modulate expression of versican. We demonstrated that wounds closed faster in transgenic mice expressing the versican 3'UTR, as compared to those in wildtype mice. We stably expressed versican 3'UTR in NIH3T3 fibroblasts and found that the 3'UTR-transfected cells showed increased migratory capacity relative to vector-transfected cells. Interestingly, we found that the 3'UTRs of versican and ß-catenin shared common microRNAs (miRNAs) including miR-185, miR-203*, miR-690, miR-680, and miR-434-3p. Luciferase assays showed that all of these miRNAs could target the 3'UTRs of both versican and ß-catenin, when the luciferase constructs contained fragments harboring the miRNA binding sites. As a consequence, expression of both versican and ß-catenin was up-regulated, which was confirmed in vitro and in vivo. Transfection with small interfering RNAs (siRNAs) targeting the versican 3'UTR abolished the 3'UTR's effects on cell migration and invasion. Taken together, these results demonstrate that versican plays important roles in wound repair and that versican messenger RNAs (mRNAs) could compete with endogenous RNAs for regulating miRNA functions.

The effect of a preoperative educational film on patients' postoperative pain in relation to their request for opioids.

Guidelines for postoperative pain treatment are based on patients' pain scores. Patients with an intermediate Numeric Rating Scale (NRS) score of 5 or 6 may consider their pain as either bearable or unbearable, which makes it difficult to decide on pain treatment because guidelines advise professionals to treat pain at NRS > 4. Educating patients in using an NRS score for pain might improve adequate pain treatment. A quasi-randomized controlled trial was conducted in which 194 preoperative patients watched the educational film and 183 the control film. Pain scores were considered discordant when patients reported an NRS ≤ 4 and wanted additional opioids or when patients reported an NRS > 4 and did not want additional opioids. Beliefs, fear, and knowledge of pain; pain assessment; and pain treatment were measured by questionnaires. No significant differences in discordant pain scores between the groups were found: relative risk (RR) 0.73, confidence interval (CI) 0.47-1.15 at rest and RR 0.96, CI 0.72-1.28 at movement. Patients in the intervention group had lower NRS pain scores than patients in the control group. In the intervention group, patients had significantly more knowledge and lower barriers to pain management compared with the control group. We did not find a statistically significant reduction in discordant pain scores when comparing the intervention group with the control group. However, patients in the intervention group had significantly lower pain scores, lower barriers, and more knowledge of pain treatment than patients in the control group.

The Relation Between Patients' NRS Pain Scores and Their Desire for Additional Opioids after Surgery.

BACKGROUND: Postoperative pain is commonly assessed through a numerical rating scale (NRS), an 11-point scale where 0 indicates no pain and 10 indicates the worst imaginable pain. Guidelines advise the administration of analgesics at NRS pain scores above 3 or 4. In clinical practice, not all patients with pain scores above the treatment threshold are willing to accept additional analgesic treatment, especially when opioids are offered. The objective of this study is to measure the relation between patients' NRS pain scores and their desire for additional opioids. METHODS: This cross-sectional study examined 1,084 patients in an academic hospital the day after surgery between January 2010 and June 2010. The day after surgery, patients were asked to score their pain and desire for opioids. Sensitivity, specificity, positive predictive value, and negative predictive value of the desire for opioids and the different NRS thresholds were calculated. RESULTS: Only when patients scored an 8 or higher on the NRS did the majority express a need for opioids. Many patients did not desire opioids, because they considered their pain tolerable, even at an NRS score above 4. CONCLUSIONS: With the current guidelines (ie, using pain scores above 3 or 4 for prescribing opioids), many patients could be overtreated. Therefore, scores generated by the NRS should be interpreted individually.

Procedure-specific risk factor analysis for the development of severe postoperative pain.

BACKGROUND: Many studies have analyzed risk factors for the development of severe postoperative pain with contradictory results. To date, the association of risk factors with postoperative pain intensity among different surgical procedures has not been studied and compared. METHODS: The authors selected precisely defined surgical groups (at least 150 patients each) from prospectively collected perioperative data from 105 German hospitals (2004-2010). The association of age, sex, and preoperative chronic pain intensity with worst postoperative pain intensity was studied with multiple linear and logistic regression analyses. Pooled data of the selected surgeries were studied with random-effect analysis. RESULTS: Thirty surgical procedures with a total number of 22,963 patients were compared. In each surgical procedure, preoperative chronic pain intensity and younger age were associated with higher postoperative pain intensity. A linear decline of postoperative pain with age was found. Females reported more severe pain in 21 of 23 surgeries. Analysis of pooled surgical groups indicated that postoperative pain decreased by 0.28 points (95% CI, 0.26 to 0.31) on the numeric rating scale (0 to 10) per decade age increase and postoperative pain increased by 0.14 points (95% CI, 0.13 to 0.15) for each higher score on the preoperative chronic pain scale. Females reported 0.29 points (95% CI, 0.22 to 0.37) higher pain intensity. CONCLUSIONS: Independent of the type and extent of surgery, preoperative chronic pain and younger age were associated with higher postoperative pain. Females consistently reported slightly higher pain scores regardless of the type of surgery. The clinical significance of this small sex difference has to be analyzed in future studies.

The effects of glucocorticoids on neuropathic pain: a review with emphasis on intrathecal methylprednisolone acetate delivery.

Methylprednisolone acetate (MPA) has a long history of use in the treatment of sciatic pain and other neuropathic pain syndromes. In several of these syndromes, MPA is administered in the epidural space. On a limited basis, MPA has also been injected intrathecally in patients suffering from postherpetic neuralgia and complex regional pain syndrome. The reports on efficacy of intrathecal administration of MPA in neuropathic pain patients are contradictory, and safety is debated. In this review, we broadly consider mechanisms whereby glucocorticoids exert their action on spinal cascades relevant to the pain arising after nerve injury and inflammation. We then focus on the characteristics of the actions of MPA in pharmacokinetics, efficacy, and safety when administered in the intrathecal space.

Chorus wave power at the strong diffusion limit overcomes electron losses due to strong diffusion.

Earth's radiation belts consist of high-energy charged particles trapped by Earth's magnetic field. Strong pitch angle diffusion of electrons caused by wave-particle interaction in Earth's radiation belts has primarily been considered as a loss process, as trapped electrons are rapidly diffused into the loss cone and lost to the atmosphere. However, the wave power necessary to produce strong diffusion should also produce rapid energy diffusion, and has not been considered in this context. Here we provide evidence of strong diffusion using satellite data. We use two-dimensional Fokker-Planck simulations of electron diffusion in pitch angle and energy to show that scaling up chorus wave power to the strong diffusion limit produces rapid acceleration of electrons, sufficient to outweigh the losses due to strong diffusion. The rate of losses saturates at the strong diffusion limit, whilst the rate of acceleration does not. This leads to the surprising result of an increase, not a decrease in the trapped electron population during strong diffusion due to chorus waves as expected when treating strong diffusion as a loss process. Our results suggest there is a tipping point in chorus wave power between net loss and net acceleration that global radiation belt models need to capture to better forecast hazardous radiation levels that damage satellites.

Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures.

BACKGROUND: Severe pain after surgery remains a major problem, occurring in 20-40% of patients. Despite numerous published studies, the degree of pain following many types of surgery in everyday clinical practice is unknown. To improve postoperative pain therapy and develop procedure-specific, optimized pain-treatment protocols, types of surgery that may result in severe postoperative pain in everyday practice must first be identified. METHODS: This study considered 115,775 patients from 578 surgical wards in 105 German hospitals. A total of 70,764 patients met the inclusion criteria. On the first postoperative day, patients were asked to rate their worst pain intensity since surgery (numeric rating scale, 0-10). All surgical procedures were assigned to 529 well-defined groups. When a group contained fewer than 20 patients, the data were excluded from analysis. Finally, 50,523 patients from 179 surgical groups were compared. RESULTS: The 40 procedures with the highest pain scores (median numeric rating scale, 6-7) included 22 orthopedic/trauma procedures on the extremities. Patients reported high pain scores after many "minor" surgical procedures, including appendectomy, cholecystectomy, hemorrhoidectomy, and tonsillectomy, which ranked among the 25 procedures with highest pain intensities. A number of "major" abdominal surgeries resulted in comparatively low pain scores, often because of sufficient epidural analgesia. CONCLUSIONS: Several common minor- to medium-level surgical procedures, including some with laparoscopic approaches, resulted in unexpectedly high levels of postoperative pain. To reduce the number of patients suffering from severe pain, patients undergoing so-called minor surgery should be monitored more closely, and postsurgical pain treatment needs to comply with existing procedure-specific pain-treatment recommendations.

Reactivity in pain-free subjects and a clinical pain population: evaluation of the Kohn Reactivity Scale-dutch Version.

BACKGROUND: Patients with pain are more reactive to various types of sensations, not limited to pain alone. A potential useful instrument to assess reactivity is the Kohn Reactivity Scale (KRS). This study examines the psychometric characteristics of the KRS-Dutch version and its ability to differentiate between subjects with and without pain. METHODS: Internal consistency, convergent validity, and test-retest reliability of the Dutch translation of the KRS were assessed in 321 pain-free control subjects and different subgroups of this sample. Subsequently, reactivity scores were compared between the pain-free subjects and 291 pain patients who were referred to a pain clinic for treatment. RESULTS: Reliability analyses indicated good internal consistency (α ≥ 0.77) and high test-retest reliability (intraclass correlation = 0.95) of the KRS in the control subjects. Validity analyses yielded positive correlations of the KRS with related constructs like pain vigilance and awareness (r = 0.37), symptom severity (r = 0.29), and the personality characteristic neuroticism (r = 0.20). Pain patients had overall significantly higher KRS scores than the pain-free subjects indicating increased reactivity, particularly for the patients with medically unexplained pain. CONCLUSIONS: These findings indicate that the KRS is a useful instrument to screen for reactivity in pain patients, which may be of particular relevance for those suffering from medically unexplained pain.

Impact of physicians' sex on treatment choices for low back pain.

BACKGROUND: Little information is available regarding physicians' sex as a potential bias in making pain treatment decisions. This study investigated how sex of the medical care provider and patient characteristics influence choices that are made in the treatment of low back pain. METHODS: Data of 186 charts of patients with low back pain (46% males) who were seen by trained residents were analyzed in this retrospective observational study. The primary outcome was the first treatment choice that was made, which was categorized in three groups: pharmacological therapy; invasive procedures; or other options at the time of first consultation. Chi-square statistics and multinominal logistic regression analysis were used to examine associations between physicians' and/or patients' sex and treatment choices. RESULTS: Physicians' sex was found to be a significant predictor of the first decision that was made in the treatment of low back pain. Female physicians tended to prescribe more pharmacological agents as their first treatment choice. No significant sex differences were found for invasive therapies or other treatment options as a first choice. These findings were found to be independent from previous received pain therapies before consultation by the specialized pain clinician. Further, patients' sex did not influence decisions on pain management nor did gender concordance or discordance in the patient-physician relationship. CONCLUSIONS: Physicians' sex had a significant impact on pain management decisions in patients with low back pain. Female physicians prescribed more pharmacological agents as their first choice compared to male physicians.

Development and validation of a radiofrequency ablation treatment planning system for vertebral metastases.

PURPOSE: Bone-targeted radiofrequency ablation (RFA) is widely used in the treatment of vertebral metastases. While radiation therapy utilizes established treatment planning systems (TPS) based on multimodal imaging to optimize treatment volumes, current RFA of vertebral metastases has been limited to qualitative image-based assessment of tumour location to direct probe selection and access. This study aimed to design, develop and evaluate a computational patient-specific RFA TPS for vertebral metastases. METHODS: A TPS was developed on the open-source 3D slicer platform, including procedural setup, dose calculation (based on finite element modelling), and analysis/visualization modules. Usability testing was carried out by 7 clinicians involved in the treatment of vertebral metastases on retrospective clinical imaging data using a simplified dose calculation engine. In vivo evaluation was performed in a preclinical porcine model (n = 6 vertebrae). RESULTS: Dose analysis was successfully performed, with generation and display of thermal dose volumes, thermal damage, dose volume histograms and isodose contours. Usability testing showed an overall positive response to the TPS as beneficial to safe and effective RFA. The in vivo porcine study showed good agreement between the manually segmented thermally damaged volumes vs. the damage volumes identified from the TPS (Dice Similarity Coefficient = 0.71 ± 0.03, Hausdorff distance = 1.2 ± 0.1 mm). CONCLUSION: A TPS specifically dedicated to RFA in the bony spine could help account for tissue heterogeneities in both thermal and electrical properties. A TPS would enable visualization of damage volumes in 2D and 3D, assisting clinicians in decisions about potential safety and effectiveness prior to performing RFA in the metastatic spine.

Beyond radiation therapy: photodynamic therapy maintains structural integrity of irradiated healthy and metastatically involved vertebrae in a pre-clinical in vivo model.

Spinal metastasis commonly occurs in advanced breast cancer. Treatment is often multimodal including radiation therapy (RT), bisphosphonates (BPs), and surgery, yet alternative minimally invasive local treatments are needed. Photodynamic therapy (PDT) has been shown to ablate tumor cells and enhance bone formation secondary to metastatic breast cancer, demonstrating potential as a treatment for spinal metastasis. Combined with previous BP treatment, bone formation was further enhanced by PDT. This study aimed to determine the effects of PDT in combination with previous RT on healthy and metastatically involved vertebrae. Forty-six athymic rats underwent RT (4 Gy on day-7), twenty-three of them were inoculated with MT-1 human breast cancer cells on day 0. Thirteen healthy and ten metastatically involved rats underwent PDT treatment on day 14. All rats were sacrificed on day 21. L2 vertebrae were analyzed using µCT imaging, mechanical testing, and histological methods. In healthy vertebrae, while modest increases in trabecular structure were found in RT + PDT compared to RT only, mechanical stability was negatively affected. The 4 Gy RT dose was found to ablate all tumor cells and prevent further vertebral metastasis. As such, in metastatically involved rats, no differences in stereological or mechanical properties were detected. RT + PDT and RT-only treatment resulted in greatly improved vertebral structural and mechanical properties versus untreated or PDT-only treatment in metastatically involved rats, due to early tumor destruction in RT-treated groups. Increased amounts of woven bone and osteoid volume were found in PDT-treated vertebrae. Further investigation is needed to understand if structural improvements seen in RT + PDT treatment can translate into longer-term improvements in strength to support the potential of PDT as a viable adjuvant treatment for spinal metastasis postradiation.

Safety assessment and pharmacokinetics of intrathecal methylprednisolone acetate in dogs.

BACKGROUND: Intrathecal methylprednisolone acetate (MPA) has been used in patients with chronic pain syndromes. Its safety has been debated after reports of adverse events. No systematic preclinical evaluation of MPA has been reported. In the current study, the acute and long-term effects of intrathecal MPA on dog spinal tissue was studied with the injectate reformulated to include minimal adjuvants. METHODS: Seventeen dogs were implanted with intrathecal catheters and randomized to three groups: vehicle (lidocaine; 4 dogs), MPA 20 mg/ml (human dose; 7 dogs), and MPA 80 mg/ml (maximum deliverable dose; 6 dogs). In parallel with the human protocols, dogs received four injections at 7-day intervals. Clinical observations and plasma methylprednisolone measurements were done before and at intervals after intrathecal delivery. One week (acute) or 6 weeks (long-term) after the last injection, animals were sacrificed and spinal tissues harvested for histopathology. RESULTS: Other than a brief motor block, no adverse clinical event occurred in any animal. Group A (vehicle) showed minimal histologic changes (median histology-score; acute: 1.3, long-term: 1.0). Group B (MPA 20 mg/ml) had a diffuse inflammatory reaction (acute: 2.0, long-term: 3.0), group C (MPA 80 mg/ml) a severe inflammatory response, with large inflammatory masses (acute: 4.0, long-term: 7.0) The severity of the inflammatory reaction increased significantly with increasing dose at long-term sacrifice (acute P = 0.167, long-term P = 0.014). No neuronal injury, demyelination, or gliosis was seen in any animal. CONCLUSION: These results, showing dose-dependent intrathecal inflammatory reactions at MPA doses and injectate concentrations comparable to those used in humans, indicate that the continued use of this modality in humans is not recommended.

Executive and attentional functions in chronic pain: does performance decrease with increasing task load?

BACKGROUND: Diminished executive function and attentional control has been reported in chronic pain patients. However, the precise pattern of impairment in these aspects of cognition in chronic pain remains unclear. Moreover, a decline in psychomotor speed could potentially influence executive and attentional control performance in pain patients. OBJECTIVE: To examine different aspects of executive and attentional control in chronic pain together with the confounding role of psychomotor slowing. METHODS: Neuropsychological tests of sustained attention, planning ability, inhibition and mental flexibility were administered to 34 participants with chronic pain and 32 control participants. RESULTS: Compared with the controls, participants with chronic pain took longer to complete tests of sustained attention and mental flexibility, but did not perform worse on inhibition or planning tasks. The decreased performance on the mental flexibility task likely reflects a reduction in psychomotor speed. The pattern of performance on the sustained attention task reveals a specific decline in attention, indicated by a disproportionate decline in performance with an increase in task duration and by increased fluctuations in attention during task performance. No additional effect was noted of pain intensity, pain duration, pain catastrophizing, depressive symptoms, reduced sleep because of the pain or opioid use. CONCLUSIONS: Executive and attention functions are not uniformly affected in chronic pain. At least part of the previously reported decline in executive function in this group may reflect psychomotor slowing. Overall, limited evidence was found that executive and attention performance is indeed lower in chronic pain. Therefore, it can be concluded that in chronic pain sustained attention performance is diminished while mental flexibility, planning and inhibition appear to be intact.