PPARγ and AKt gene modulation following pregabalin and duloxetine combination for painful diabetic polyneuropathy.

Aim: Diabetic peripheral neuropathy (DPN) induces chronic neuropathic pain in diabetic patients. Current treatments like pregabalin and duloxetine offer limited efficacy. This study evaluates combining pregabalin and duloxetine versus pregabalin alone for DPN pain relief, and explores gene modulation (PPARγ and Akt) to understand neuropathic pain's molecular basis. Materials & methods: Diabetic patients with DPN were randomized into groups receiving combination therapy or pregabalin alone for 4 weeks. Pain intensity, gene expression and quality of life were assessed. Results: Combination therapy significantly reduced pain, improved quality of life and upregulated PPARγ and Akt genes compared with monotherapy. Conclusion: Pregabalin and duloxetine combination therapy in DPN led to PPARγ mRNA upregulation and negative correlation of Akt gene expression with pain scores. This combination therapy effectively reduced pain and improved quality of life.Clinical Trial Registration: CTRI/2021/02/031068.

Combining medicines to reduce nerve pain in diabetic patientsWhat is this article about? People with diabetes often have nerve pain called diabetic peripheral neuropathy (DPN). Some medicines like pregabalin and duloxetine help, but are not enough. This study tested if using both medicines together works better than using just pregabalin. The study also looked at how these medicines affect certain genes.What were the results? Patients with DPN took either both medicines or just pregabalin for 4 weeks. The combined treatment reduced pain, improved life quality and affected certain genes.What do the results of the study mean? Using pregabalin and duloxetine together can reduce DPN pain more effectively. This offers hope for better treatment options.

GIBPS technique-a novel sequential technique of performing shoulder corticosteroid injections.

The introduction of the xxxxxxxx (GIBPS) technique represents a patient-centric novel and innovative method of ultrasound guided corticosteroid injection targeting the Glenohumeral joint (GHJ) and the Subacromial-Subdeltoid (SASD) bursa in a sequential manner, in the same setting. By integrating the two different sites of injection into a single technique, the procedure has the potential of transforming musculoskeletal interventional radiology and maximising patient care in shoulder pathologies. This procedure aims to reduce patient discomfort, optimise procedural efficiency, and enhance treatment precision through ultrasound guidance and improve the overall patient experience.

Case report: Spinal cord stimulation for pain relief in two patients with locally recurrent pelvic malignancy.

Introduction: Chronic cancer-related pain from locally recurrent infiltrative cancers within the bony confines of the pelvis is a devastating and hard to manage condition that can be refractory to many conventional pain management methods. Spinal cord stimulation (SCS) is an evolving and safe method of pain management and can be trialled in a quick and well-tolerated operation under local anaesthesia. To date, this has not been reported in the setting of locally recurrent inoperable pelvic cancers. Case description: In the present study, we report two cases of patients with severe back and lower limb pain resulting from recurrent anal and rectal cancers involving the right lumbar and sacral nerve roots as well as the bony sacrum, which severely affected quality of life and daily functioning. Discussion: Following successful SCS, effective pain relief was observed. Conclusion: SCS could represent an effective supplementary or alternative technique to conventional pain management in this challenging group of patients, especially if other available methods have been exhausted.

Paravertebrally-Injected Multifunctional Hydrogel for Sustained Anti-Inflammation and Pain Relief in Lumbar Disc Herniation.

Pain caused by lumbar disc herniation (LDH) severely compromises patients' quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH-induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally-injected multifunctional hydrogel that can efficiently co-load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti-inflammation, reactive oxygen species (ROS)-removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS-responsive crosslinker to form amphiphilic polymer that self-assemble into particles with ropivacaine loaded into the core. Solution of drug-loaded particles and thermo-sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro-inflammatory cytokines and pain-related molecules including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). Therapeutic hydrogel suppresses the LDH-induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine-related diseases.

In situ pain relief during photodynamic therapy by ROS-responsive nanomicelle through blocking VGSC.

Pain in photodynamic therapy (PDT), resulting from the stimulation of reactive oxygen species (ROS) and local acute inflammation, is a primary side effect of PDT that often leads to treatment interruption or termination, significantly compromising the efficacy of PDT and posing an enduring challenge for clinical practice. Herein, a ROS-responsive nanomicelle, poly(ethylene glycol)-b-poly(propylene sulphide) (PEG-PPS) encapsulated Ce6 and Lidocaine (LC), (ESCL) was used to address these problems. The tumor preferentially accumulated micelles could realize enhanced PDT effect, as well as in situ quickly release LC due to its ROS generation ability after light irradiation, which owes to the ROS-responsive property of PSS. In addition, PSS can suppress inflammatory pain which is one of the mechanisms of PDT induced pain. High LC-loaded efficiency (94.56 %) owing to the presence of the thioether bond of the PPS made an additional pain relief by inhibiting excessive inflammation besides blocking voltage-gated sodium channels (VGSC). Moreover, the anti-angiogenic effect of LC offers further therapeutic effects of PDT. The in vitro and in vivo anti-tumor results revealed significant PDT efficacy. The signals of the sciatic nerve in mice were measured by electrophysiological study to evaluate the pain relief, results showed that the relative integral area of neural signals in ESCL-treated mice decreased by 49.90 % compared to the micelles without loaded LC. Therefore, our study not only develops a very simple but effective tumor treatment PDT and in situ pain relief strategy during PDT, but also provides a quantitative pain evaluation method.

Effectiveness of exercise programs to reduce low back pain among nurses and nursing assistants: A systematic review and meta-analysis.

INTRODUCTION: Nurses have a high prevalence of low back pain due to ergonomic hazards in healthcare workplaces. While exercise programs have been suggested as an intervention strategy, the effectiveness of low back pain programs has been inconsistent in the research literature. The purpose of study is to determine the effect of exercise programs to reduce low back pain among nursing staff. METHODS: A systematic review and meta-analysis was conducted with five databases and systematically searched. Following the PRISMA guidelines, included studies evaluated low back pain relief among nurses or nursing assistants and described the exercise program. Two reviewers independently appraised, extracted, and synthesized all available studies. The study protocol was registered in PROSPERO (CRD42022359511). RESULTS: A total of 296 articles with 1,355 nursing staff from nine countries were obtained. Nine randomized controlled trials with a moderate to low risk of bias quality were included. Exercise programs had a small but significant effect on low back pain of nursing staff (SMD = -0.48; 95% CI = -0.76 to -0.19; p = 0.03, I2 = 62%, p = 0.001). A subgroup analysis of nurses and nursing assistants showed moderate and small effects, respectively (I2 = 0% p < 0.0001, SMD -0.73 CI 95% [-0.97 to -0.48], p = 0.76, and I2 = 0% p = 0.002, SMD -0.23 CI 95% [-0.38 to -0.08], p < 0.88). Exercise for back and trunk exhibited a moderate effect on low back pain (SMD -0.56 CI 95% [-0.86 to -0.25], p = 0.01, I2 = 66%, p < 0.0004). A subgroup analysis comparing age, under 40 years old revealed a moderate effect size (SMD = -0.59; 95% CI = -0.83to -0.35; p = 0.06; I2 = 64%, p < 0.0001). CONCLUSIONS: Exercise programs are an effective treatment to reduce low back pain in nurses and nursing assistants, especially among younger staff. PRACTICAL APPLICATION: Back and trunk exercise programs should be recommended for nursing staff with low back pain.

Regimes of pain: The geopolitics of cancer palliation in Pakistan.

This article examines how militarized regimes of narcotics and price control sustain unpalliated cancer pain in Pakistan. It shows how these regimes of control-reimagined as "regimes of pain"-render morphine, a cheap, effective opiate analgesic, scarce in hospitals. Meanwhile, heroin, morphine's illegal derivative, proliferates in illicit circuits. The article highlights a devastating consequence of the global wars against drugs and "terror": the consignment of cancer patients to agonizing end-of-life pain. Widening the analytic lens upon palliation beyond bodies and their clinical encounters, the article offers a geopolitics of palliation. It shows how narcovigilance targeting illicit drugs has the perverse effect of throttling morphine's licit supply. It shows further how unviably low price ceilings, purported to ensure a poor population's access to morphine, render it scarce on the official market. These mutually reinforcing regimes of control thus thwart their own purported objectives, consigning cancer patients to preventable, yet unpalliated, pain.

Repeated epidural delivery of Shinbaro2: effects on neural recovery, inflammation, and pain modulation in a rat model of lumbar spinal stenosis.

The choice of treatment for lumbar spinal stenosis (LSS) depends on symptom severity. When severe motor issues with urinary dysfunction are not present, conservative treatment is often considered to be the priority. One such conservative treatment is epidural injection, which is effective in alleviating inflammation and the pain caused by LSS-affected nerves. In this study, Shinbaro2 (Sh2), pharmacopuncture using natural herbal medicines for patients with disc diseases, is introduced as an epidural to treat LSS in a rat model. The treatment of primary sensory neurons from the rats' dorsal root ganglion (DRG) neurons with Sh2 at various concentrations (0.5, 1, and 2 mg/mL) was found to be safe and non-toxic. Furthermore, it remarkably stimulated axonal outgrowth even under H2O2-treated conditions, indicating its potential for stimulating nerve regeneration. When LSS rats received epidural injections of two different concentrations of Sh2 (1 and 2 mg/kg) once daily for 4 weeks, a significant reduction was seen in ED1+ macrophages surrounding the silicone block used for LSS induction. Moreover, epidural injection of Sh2 in the DRG led to a significant suppression of pain-related factors. Notably, Sh2 treatment resulted in improved locomotor recovery, as evaluated by the Basso, Beattie, and Bresnahan scale and the horizontal ladder test. Additionally, hind paw hypersensitivity, assessed using the Von Frey test, was reduced, and normal gait was restored. Our findings demonstrate that epidural Sh2 injection not only reduced inflammation but also improved locomotor function and pain in LSS model rats. Thus, Sh2 delivery via epidural injection has potential as an effective treatment option for LSS.

EFFECTIVENESS OF DORSAL ROOT GANGLION STIMULATION IN CHRONIC PAIN MANAGEMENT: A SYSTEMATIC REVIEW.

OBJECTIVE: This systematic review aims to determine the effectiveness of Dorsal Root Ganglion Stimulation (DRGS) in chronic pain management. MATERIALS AND METHODS: In 2023, a comprehensive systematic review was undertaken utilizing various electronic databases, employing MeSH terms and free search terms tailored to the study's aims. This review included primary research such as cohorts, case-control studies, and clinical trials, all focusing on the efficacy of DRGS in treating various chronic pain conditions. Non-human or animal studies were omitted from the selection process. A review of study quality was conducted, followed by meticulous analysis of the findings to synthesize the evidence. This review represents the most current research, with updates extending to 2024. A total of 400 articles were reviewed. 29 articles were included in our review after meticulous screening. RESULTS: Twenty-nine articles published in the last five years meeting selection criteria were identified, encompassing patients with various diagnoses warranting the use of DRGS beyond CRPS. Additionally, the analysis includes different outcome measurement tools, emphasizing improvements in pain management, functionality, and quality of life. Finally, common complications such as surgical site infection and issues with electrodes are highlighted. CONCLUSIONS: This systematic review affirms the effectiveness of DRGS therapy in managing diverse chronic pain conditions, highlighting improvements in quality of life, functionality, and mood states, making it a viable alternative for patients unresponsive to traditional treatments.

Efficacy and Safety of Pharmacological Treatment in Patients with Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis.

Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved pharmacological treatment for patients with CRPS. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological therapies and determine the best strategy for CRPS. We searched the databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov, for published eligible randomized controlled trials (RCTs) comparing pharmacological treatment with placebo in CRPS patients. Target patients were diagnosed with CRPS according to Budapest Criteria in 2012 or the 1994 consensus-based IASP CRPS criteria. Finally, 23 RCTs comprising 1029 patients were included. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty (confidence in evidence and quality of evidence). Direct meta-analysis showed that using bisphosphonates (BPs) (mean difference [MD] -2.21, 95% CI -4.36--0.06, p = 0.04, moderate certainty) or ketamine (mean difference [MD] -0.78, 95% CI -1.51--0.05, p = 0.04, low certainty) could provide long-term (beyond one month) pain relief. However, there was no statistically significant difference in the efficacy of short-term pain relief. Ketamine (rank p = 0.55) and BPs (rank p = 0.61) appeared to be the best strategies for CRPS pain relief. Additionally, BPs (risk ratio [RR] = 1.86, 95% CI 1.34-2.57, p < 0.01, moderate certainty) and ketamine (risk ratio [RR] = 3.45, 95% CI 1.79-6.65, p < 0.01, moderate certainty) caused more adverse events, which were mild, and no special intervention was required. In summary, among pharmacological interventions, ketamine and bisphosphonate injection seemed to be the best treatment for CRPS without severe adverse events.

No pain relief by virtual reality during hysterosalpingography (HSG): results from a randomized controlled trial.

STUDY QUESTION: Is virtual reality (VR) an effective non-pharmacological tool to reduce procedural pain during hysterosalpingography (HSG)? SUMMARY ANSWER: An HSG with VR does not reduce procedural pain scores compared to an HSG without VR. WHAT IS KNOWN ALREADY: An HSG is often experienced as painful and uncomfortable. VR has been proven successful to reduce acute procedural pain during a variety of medical procedures and interventions. STUDY DESIGN, SIZE, DURATION: We performed a two-centre open-label randomized controlled trial between January 2021 and October 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women scheduled for HSG as part of their infertility work-up were screened for participation. After informed consent, women were randomized between HSG with or without VR. Due to the nature of the intervention, the study was not blinded. VR was administered by a head-mounted device displaying nature movies and/or relaxation exercises. The primary endpoint was procedural pain measured using VAS (scale 0.0-10.0 cm). Procedural pain was divided into overall pain score and peak pain score during the procedure. It was measured immediately after HSG. Secondary endpoints included patient satisfaction, VR preferences, and adverse effects of VR. MAIN RESULTS AND THE ROLE OF CHANCE: We included a total of 134 women, 69 to the intervention group (HSG with VR) and 65 to the control group (HSG without VR). The mean VAS for peak pain was 6.80 cm (SD 2.25) in the intervention group versus 6.60 cm (SD 2.40) in the control group (mean difference 0.28 (95% CI -0.57, 1.12), P = 0.52). The mean VAS for overall pain was 5.00 cm (SD 2.10) in the intervention group versus 4.90 cm (SD 2.13) in the control group (mean difference 0.06 (95% CI -0.71, 0.84), P = 0.88). The expectation that VR would be a good distraction from pain during HSG was correlated with both overall and peak pain scores. When correcting for this expectation, we found that women in the intervention group reported significantly higher scores, both in peak (adjusted MD 0.58 (95% CI -0.81, 1.97), P = 0.021) and overall (adjusted MD 0.43 (95% CI -0.84, 1.71), P = 0.013) pain, compared to the control group. There were no differences in the prevalence of symptoms that were considered as adverse effects of VR. LIMITATIONS, REASONS FOR CAUTION: The study was not blinded. Reasons for declining participation in the study were anxiety or wanting full control during HSG, which might have created selection bias. The distraction score possibly indicates that the level of VR immersiveness was not optimal due to the lack of sound and/or the type of VR applications. Future studies should investigate whether more immersive or interactive VR applications could decrease procedural pain scores during HSG. WIDER IMPLICATIONS OF THE FINDINGS: Since VR does not reduce procedural pain, this additional tool should not be used during HSG. STUDY FUNDING/COMPETING INTEREST(S): There was no external funding for this study. KR and AvH report receiving a travel grant from Merck outside the scope of this study. BM is supported by a National Health and Medical Research Council (NHMRC) investigator grant (GNT1176437) and BM reports consultancy for Merck, Organon, and Norgine and travel and research funding from Merck. BM holds stock for ObsEva. CL reports receiving research grants from Merck, and Ferring. KD and VM report receiving travel and speaker's fees from Guerbet and research grants from Guerbet. VM also reports research grants from Merck and Ferring. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER: The trial is registered prospectively in the Netherlands Trial Register (trialregister.nl registration number NL9203, currently accessible on trialsearch.who.int). TRIAL REGISTRATION DATE: 16-01-2021. DATE OF FIRST PATIENT'S ENROLMENT: The first participant was enrolled on 19 January 2021.

Recent advances in the treatment of oral ulcerative mucositis from clinical and basic perspectives.

BACKGROUND: Oral ulcerative mucositis (OUM) is common in patients with cancer, particularly in those undergoing chemoradiation therapy. The effective management of OUM is crucial for continuous cancer care and patient well-being. Recent studies have advanced our understanding of the causes, leading to clinical trials toward novel treatments. This review focuses on the contemporary therapeutic landscape, and provides the latest insights into the mechanisms of mucosal healing and pain. HIGHLIGHTS: Management strategies for oral ulcerative mucositis in patients with cancer include maintaining good oral hygiene, reducing mucosal irritation against radiation, and using various topical analgesic treatments, including herbal medicines. However, the current management practices have limitations that necessitate the development of more efficacious and novel treatments. Molecular research on transient receptor potential (TRP) channels in the oral mucosa is crucial for understanding the mechanisms of wound healing and pain in patients with OUM. Targeting TRP subfamily V member 3 (V3) and TRPV4 can enhance wound healing through re-epithelialization. The suppression of TRPV1, TRPA1, and TRPV4 may be effective in alleviating OUM-induced pain. CONCLUSION: Research advancements have improved our understanding and potentially led to novel treatments that offer symptomatic relief. This progress highlights the importance of collaborations between clinical researchers and scientists in the development of innovative therapies.

Unraveling the Tapestry of Pain: A Comprehensive Review of Ethnic Variations, Cultural Influences, and Physiological Mechanisms in Pain Management and Perception.

The medical management of pain is a nuanced challenge influenced by sociocultural, demographic, and ethical factors. This review explores the intricate interplay of these dimensions in shaping pain perception and treatment outcomes. Sociocultural elements, encompassing cultural beliefs, language, societal norms, and healing practices, significantly impact individuals' pain experiences across societies. Gender expectations further shape these experiences, influencing reporting and responses. Patient implications highlight age-related and socioeconomic disparities in pain experiences, particularly among the elderly, with challenges in managing chronic pain and socioeconomic factors affecting access to care. Healthcare provider attitudes and biases contribute to disparities in pain management across racial and ethnic groups. Ethical considerations, especially in opioid use, raise concerns about subjective judgments and potential misuse. The evolving landscape of placebo trials adds complexity, emphasizing the importance of understanding psychological and cultural factors. In conclusion, evidence-based guidelines, multidisciplinary approaches, and tailored interventions are crucial for effective pain management. By acknowledging diverse influences on pain experiences, clinicians can provide personalized care, dismantle systemic barriers, and contribute to closing knowledge gaps, impacting individual and public health, well-being, and overall quality of life.

Effect of percutaneous electrical stimulation at the Baliao point on preventing postpartum urinary retention after labor analgesia.

BACKGROUND: Anesthetic drugs used in labor analgesia also paralyze the bladder muscle by blocking the sacral plexus, thereby affecting maternal postpartum spontaneous urination and increasing the risk of postpartum urinary retention (PUR). AIM: To analyze the effect of percutaneous electrical stimulation at the Baliao point combined with biofeedback therapy for PUR prevention. METHODS: We selected 182 pregnant women who received labor analgesia in obstetrics between June 2022 and December 2023. They were divided into the combined therapy group (transcutaneous electrical stimulation of the Baliao point combined with biofeedback therapy) and the control group (biofeedback therapy alone). The first spontaneous urination time, first postpartum urine volume, bladder residual urine volume, postpartum hemorrhage volume, pre-urination waiting time, PUR incidence, adverse reactions, and the intervention's clinical efficacy were compared between the two groups. RESULTS: The first spontaneous urination time after delivery was more delayed (2.92 ± 1.04 h vs 3.61 ± 1.13 h, P < 0.001), with fewer initial postpartum urine (163.54 ± 24.67 mL vs 143.72 ± 23.95 mL, P < 0.001), more residual bladder urine (54.81 ± 10.78 mL vs 65.25 ± 13.52 mL, P < 0.001), more postpartum bleeding (323.15 ± 46.95 mL vs 348.12 ± 45.03 mL, P = 0.001), and longer waiting time for urination (0.94 ± 0.31 min vs 1.29 ± 0.42 min, P < 0.001), in the control group than in the combined therapy group. The control group also had higher PUR incidence (4.65% vs 15.85%, P = 0.016). Both groups had no adverse reactions, but the clinical total efficacy rate of the intervention was significantly higher in the combined therapy group than in the control group (95.35% vs 84.15%, P = 0.016). CONCLUSION: Percutaneous electrical stimulation of the Baliao point combined with biofeedback can significantly promote postpartum micturition of parturients with labor analgesia, thereby effectively preventing PUR occurrence.

Risk factors, associations, and high-risk patient profiles for nocturnal pain in carpal tunnel syndrome: implications for patient care.

INTRODUCTION: Carpal tunnel syndrome results from chronic compression of the median nerve, causing pain and paresthesia, especially at night. The impact of these symptoms on patients includes disrupted sleep patterns and a desire to alleviate discomfort through hand movements. Our study aims to investigate risk factors, associations, and high-risk patient profiles associated with these nocturnal manifestations in carpal tunnel syndrome. METHODOLOGY: Utilizing a retrospective case-control design, our study comprises 681 patients with carpal tunnel syndrome, including 581 with nocturnal symptoms and 90 without. Data were obtained through personalized phone calls and health records, covering health profiles, medical comorbidities, perioperative variables, and selected outcomes. RESULTS: Analyzing 591 patients with night symptoms revealed significant differences compared to the non-night symptoms group. The night symptoms group exhibited a lower mean age (51.3 vs. 56.6 years, p = 0.001), higher prevalence of diabetes (30.1% vs. 45.6%, p = 0.003), and paresthesia (98.5% vs. 81.1%, p < 0.001). In addition, the night symptoms group reported a higher incidence of disabling pain (89.2% vs. 70.0%, p < 0.001), weak hand grip (80.5% vs. 62.2%, p < 0.001), and night splints use (37.7% vs. 24.4%, p < 0.001). Preoperatively, the night symptoms group exhibited slightly higher intraoperative anxiety (40.9% vs. 30.0%, p = 0.12) and a slightly longer recovery time (1.7 vs. 1.4 months, p = 0.22), with no significant difference in pain relief scores (8.1 vs. 7.7, p = 0.16). CONCLUSION: Patients with night symptoms show increased likelihood of comorbidities (diabetes, and renal, conditions), along with a propensity for disabling symptoms and paresthesia. Although they experience slightly longer recovery times, they demonstrate improved pain relief scores. LEVEL OF EVIDENCE III: Case-Control Study.

Perioperative Cannabinoids Significantly Reduce Postoperative Opioid Requirements in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Background Opioids, commonly used to control pain associated with surgery, are known to prolong the duration of mechanical ventilation and length of hospital stay. A wide range of adjunctive strategies are currently utilized to reduce postoperative pain, such as local and regional nerve blocks, nerve cryoablation, and adjunctive medications. We hypothesized that dronabinol (a synthetic cannabinoid) in conjunction with standard opioid pain management will reduce opioid requirements to manage postoperative pain. Methods Sixty-eight patients who underwent isolated first-time coronary artery bypass graft surgery were randomized to either the control group, who received only standard opioid-based analgesia, or the dronabinol group, who received dronabinol (a synthetic cannabinoid) in addition to standard opioid-based analgesia. Dronabinol was given in the preoperative unit, before extubation in the ICU, and after extubation on the first postoperative day. Preoperative, intraoperative, and postoperative parameters were compared under an IRB-approved protocol. The primary endpoints were the postoperative opioid requirement, duration of mechanical ventilation, and ICU length of stay, and the secondary endpoints were the duration of inotropic support needed, left ventricular ejection fraction (LVEF), and the change in LVEF. This study was undertaken at Northwest Medical Center, Tucson, AZ, USA. Results Sixty-eight patients were randomized to either the control group (n = 37) or the dronabinol group (n = 31). Groups were similar in terms of demographic features and comorbidities. The total postoperative opioid requirement was significantly lower in the dronabinol group [39.62 vs 23.68 morphine milligram equivalents (MMEs), p = 0.0037], representing a 40% reduction. Duration of mechanical ventilation (7.03 vs 6.03h, p = 0.5004), ICU length of stay (71.43 vs 63.77h, p = 0.4227), and inotropic support requirement (0.6757 vs 0.6129 days, p = 0.7333) were similar in the control and the dronabinol groups. However, there was a trend towards lower durations in each endpoint in the dronabinol group. Interestingly, a significantly better preoperative to postoperative LVEF change was observed in the dronabinol group (3.51% vs 6.45%, p = 0.0451). Conclusions Our study found a 40% reduction in opioid use and a significantly greater improvement in LVEF in patients treated with adjunctive dronabinol. Mechanical ventilation duration, ICU length of stay, and inotropic support requirement tended to be lower in the dronabinol group, though did not reach statistical significance. The results of this study, although limited by sample size, are very encouraging and validate our ongoing investigation.

Effect of saline irrigation temperature difference on postoperative acute pain and hypothermia during biportal endoscopic spine surgery.

BACKGROUND: Recently, enhanced recovery after surgery (ERAS) protocols have attracted attention; they emphasize on avoiding intraoperative hypothermia while performing lumbar fusion surgery. However, none of the studies have reported the protocol for determining the temperature of saline irrigation during biportal endoscopic spine surgery (BESS) procedure. This study evaluated the effectiveness of warm saline irrigation during BESS in acute postoperative pain and inflammatory reactions. MATERIALS AND METHODS: Fifty-five patients who underwent BESS procedure were retrospectively analyzed for the incidence of perioperative hypothermia (< 36oC), postoperative inflammatory factors (white blood cells (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA)), and clinical outcomes (back visual analog scale (VAS) score, postoperative shivering). The patients were divided into the warm and cold saline irrigation groups. RESULTS: Hemoglobin, WBC, ESR, creatine kinase, and creatine kinase-muscle brain levels did not significantly differ between the warm and cold saline groups. The mean CRP, IL-6, and SAA levels were significantly higher in the cold saline group than in the warm saline group (p = 0.0058, 0.0028, and 0.0246, respectively); back VAS scores were also higher with a statistically significant difference until two days postoperatively (p < 0.001). During the entire procedure, the body temperature was significantly lower in the cold saline irrigation group, but the hypothermia incidence rate significantly differed 30 min after the operation was started. CONCLUSIONS: Using warm saline irrigation during BESS is beneficial for early recovery after surgery, as it is associated with reduced postoperative pain and complication rates.

Efficacy of Episil® in patients with hematologic malignancies: a comparative study.

BACKGROUND: Episil® is a nonabsorbable liquid medical material used to coat and protect the mucosa in patients with oral mucositis. A few studies have reported its efficacy in patients with head and neck cancer. However, reports on its use in patients with hematologic malignancies are scarce. Thus, we aimed to evaluate the efficacy of Episil for the treatment of oral mucositis in patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome. METHODS: Between May 2018 and March 2019, a total of thirty-seven patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome who received Episil® for the treatment of oral mucositis were included in this study. All patients were treated at the Hiroshima Red Cross and Atomic-bomb Surgery Hospital. To determine the severity of oral mucositis, 22 out of the 37 patients were interviewed and compared objectively using the Common Terminology Criteria for Adverse Events, version 3.0. In addition, subjective measures of the effects of oral mucositis were assessed using an original evaluation protocol (a unique evaluation chart specific to the Department of Oral Surgery, Hiroshima Red Cross & Atomic-bomb Survivors Hospital). RESULTS: Out of 37 participants recruited in the study, 31 (84%) described the sensation of Episil® as very good or good. Moreover, the severity of mucositis was found to decrease after the use of Episil® in seven patients out of 22 (19%), particularly in those with mucositis at multiple sites. Participants' evaluations revealed pain relief and improvement in speech and feeding functions. Participants with grade 3 mucositis reported a greater improvement in pain relief, speech, and feeding functions than those with grade 2 mucositis. CONCLUSIONS: This study suggests the efficacy of Episil® in treating oral mucositis in patients with hematologic malignancies, particularly in those with oral mucositis at multiple sites. In addition to pain relief, Episil® may improve speech and feeding functions.

Assessment of pain relief after four botulinum toxin A injection cycles in patients with post-stroke lower limb spasticity: A prospective, observational study.

INTRODUCTION: Spasticity is common after a stroke and is an independent risk factor for developing pain. BotulinumtoxinA injection is the treatment of choice for focal spasticity. We examined the effect of intramuscular botulinumtoxinA on pain relief in patients in routine clinical practice who were experiencing pain as a primary complaint associated with post-stroke lower limb spasticity. METHODS: Prospective, multicentre, post-marketing observational study. The study period was 16 months. The primary effectiveness variable was the mean change from baseline on the pain 0-10 Numerical Rating Scale after four botulinumtoxinA injection cycles. Secondary endpoints included changes from baseline on the pain 0-100 Visual Analogue Scale, Goal Attainment Scale, modified Ashworth Scale, 10-Meter Walk Test, Penn Spasm Frequency Scale, and 36-item Short-Form Health Survey. RESULTS: Of 186 enrolled patients, 180 (96.8%) received botulinumtoxinA at least once. The mean (standard deviation) pain 0-10 Numerical Rating Scale score decreased significantly (p<0.0001) from 4.9 (2.2) at baseline to 2.5 (2.1) at study end, representing a 50% decrease in pain severity. Relief of pain due to spasticity was supported by improvement from baseline in all secondary variables except the 10-Meter Walk Test. Two adverse events (erysipelas and phlebitis) in one patient were considered likely to be related to botulinumtoxinA injection. CONCLUSION: BotulinumtoxinA appears to provide pain relief as an additional benefit of local treatment in patients with post-stroke lower limb spasticity for whom pain relief is a primary therapeutic goal (a Lay Abstract has been provided as Appendix A).

Photobiomodulation for pain relief: Model-based estimates of effective doses of light at the neural target.

INTRODUCTION: Photobiomodulation (PBM) has been studied since the 1960s as a clinical tool. More recently, PBM has been observed to reduce compound action potential components and hypersensitivities associated with neuropathic pains. However, no definitive description of efficacious light parameters has been determined. Some reasons may be that previous meta-analyses and reviews have focused on emitter output rather than the light at the target tissue and have included data sets that are large but with notable variability (e.g., combining data from various disease etiologies, and data from PBM at various wavelengths). This fact has made it difficult to successfully define the range of effective parameters. METHODS: In this study, photon propagation software was used to estimate irradiance at a target nerve using several published data sets chosen for their narrow criteria to minimize variability. Utilizing these estimates, effective and ineffective light irradiances at the nerve of interest for wavelengths of 633 nm or 808-830 nm were examined and estimated. These estimates are focused on the amount of light required to achieve a reduction in pain or a surrogate measure via a hypothesized nerve block mechanism. RESULTS: Accounting for irradiance at the target nerve yielded a clear separation of PBM doses that achieved small-fiber nerve block from those that did not. For both the 633 nm group and the 808-830 group, the irradiance separation threshold followed a nonlinear path with respect to PBM application duration, where shorter durations required higher irradiances, and longer durations required lower irradiances. Using the same modeling methods, irradiance was estimated as a function of depth from a transcutaneous source (distance from skin surface) for emitter output power using small or large emitter sizes. CONCLUSION: Taken together, the results of this study can be used to estimate effective PBM dosing schemes to achieve small-fiber inhibition for various anatomical scenarios.