Patient-controlled intravenous morphine analgesia combined with transcranial direct current stimulation for post-thoracotomy pain: A cost-effectiveness study and a feasibility for its future implementation

This prospective randomized study aims to evaluate the feasibility and cost-effectiveness of combining transcranial direct current stimulation (tDCS) with patient controlled intravenous morphine analgesia (PCA-IV) as part of multimodal analgesia after thoracotomy. Patients assigned to the active treatment group (a-tDCS

Effect of transcranial direct current stimulation combined with patient-controlled intravenous morphine analgesia on analgesic use and post-thoracotomy pain. A prospective, randomized, double-blind, sham-controlled, proof-of-concept clinical trial

Background: Transcranial direct current stimulation (tDCS) is used for various chronic pain conditions, but experience with tDCS for acute postoperative pain is limited. This study investigated the effect of tDCS vs. sham stimulation on postoperative morphine consumption and pain intensity after thoracotomy. Methods: This is a single-center, prospective, randomized, double-blind, sham-controlled trial in lung cancer patients undergoing thoracotomy under general anesthesia. All patients received patient-controlled (PCA) intravenous morphine and intercostal nerve blocks at the end of surgery. The intervention group (a-tDCS, n = 31) received anodal tDCS over the left primary motor cortex (C3-Fp2) for 20 min at 1.2 mA, on five consecutive days; the control group (n = 31) received sham stimulation. Morphine consumption, number of analgesia demands, and pain intensity at rest, with movement and with cough were recorded at the following intervals: immediately before (T1), immediately after intervention (T2), then every hour for 4 h (Т3-Т6), then every 6 h (Т7-Т31) for 5 days. We recorded outcomes on postoperative days 1 and 5 and conducted a phone interview inquiring about chronic pain 1 year later (NCT03005548). Results: A total of 62 patients enrolled, but tDCS was prematurely stopped in six patients. Fifty-five patients (27 a-tDCS, 28 sham) had three or more tDCS applications and were included in the analysis. Cumulative morphine dose in the first 120 h after surgery was significantly lower in the tDCS [77.00 (54.00-123.00) mg] compared to sham group [112.00 (79.97-173.35) mg, p = 0.043, Cohen\u27s d = 0.42]. On postoperative day 5, maximum visual analog scale (VAS) pain score with cough was significantly lower in the tDCS group [29.00 (20.00-39.00) vs. 44.50 (30.00-61.75) mm, p = 0.018], and pain interference with cough was 80% lower [10.00 (0.00-30.00) vs. 50.00 (0.00-70.00), p = 0.013]. One year after surgery, there was no significant difference between groups with regard to chronic pain and analgesic use. Conclusion: In lung cancer patients undergoing thoracotomy, three to five tDCS sessions significantly reduced cumulative postoperative morphine use, maximum VAS pain scores with cough, and pain interference with cough on postoperative day 5, but there was no obvious long-term benefit from tDCS

Efficacy results of pimavanserin from a multi-center, open-label extension study in Parkinson's disease psychosis patients

© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.Introduction: Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved for hallucinations and delusions associated with Parkinson's disease psychosis (PDP). We present durability of response with pimavanserin in patients with PDP for an additional 4 weeks of treatment. Methods: This was an open-label extension (OLE) study in patients previously completing one of three double-blind, placebo-controlled (Core) studies. All patients received pimavanserin 34 mg once daily. Efficacy assessments included the Scale for the Assessment of Positive Symptoms (SAPS) PD and H + D scales, Clinical Global Impression (CGI) Improvement and Severity scales and Caregiver Burden Scale (CBS), through 4 weeks in the OLE. Safety assessments were conducted at each visit. Results: Of 459 patients, 424 (92.4%) had a Week 4 efficacy assessment. At Week 4 (10 weeks total treatment), SAPS-PD mean (standard deviation) change from OLE baseline was -1.8 (5.5) and for SAPS-H + D was -2.1 (6.2) with pimavanserin 34 mg. Patients receiving placebo during the Core studies had greater improvements (SAPS-PD -2.9 [5.6]; SAPS-H + D -3.5 [6.3]) during the OLE. For participants treated with pimavanserin 8.5 or 17 mg during the Core studies, further improvement was observed during the OLE with pimavanserin 34 mg. The mean change from Core Study baseline for SAPS-PD score was similar among prior pimavanserin 34 mg and prior placebo-treated participants (-7.1 vs. -7.0). The CGI-I response rate (score of 1 or 2) at Week 4 was 51.4%. Adverse events were reported by 215 (46.8%) patients during the first 4 weeks of OLE. The most common AEs were fall (5.9%), hallucination (3.7%), urinary tract infection (2.8%), insomnia (2.4%), and peripheral edema (2.2%) CONCLUSIONS: Patients previously on pimavanserin 34 mg during three blinded core studies had durability of efficacy during the subsequent 4 week OLE SAPS-PD assessment. Patients previously on blinded placebo improved after 4 weeks of OL pimavanserin treatment. These results in over 400 patients from 14 countries support the efficacy of pimavanserin for treating PDP.info:eu-repo/semantics/publishedVersio

Patient-Controlled Intravenous Morphine Analgesia Combined with Transcranial Direct Current Stimulation for Post-Thoracotomy Pain: A Cost-Effectiveness Study and A Feasibility for Its Future Implementation

This prospective randomized study aims to evaluate the feasibility and cost-effectiveness of combining transcranial direct current stimulation (tDCS) with patient controlled intravenous morphine analgesia (PCA-IV) as part of multimodal analgesia after thoracotomy. Patients assigned to the active treatment group (a-tDCS, n = 27) received tDCS over the left primary motor cortex for five days, whereas patients assigned to the control group (sham-tDCS, n = 28) received sham tDCS stimulations. All patients received postoperative PCA-IV morphine. For cost-effectiveness analysis we used data about total amount of PCA-IV morphine and maximum visual analog pain scale with cough (VASP-Cmax). Direct costs of hospitalization were assumed as equal for both groups. Cost-effectiveness analysis was performed with the incremental cost-effectiveness ratio (ICER), expressed as the incremental cost (RSD or US$) per incremental gain in mm of VASP-Cmax reduction. Calculated ICER was 510.87 RSD per VASP-Cmax 1 mm reduction. Conversion on USA market (USA data 1.325 US$ for 1 mg of morphine) revealed ICER of 189.08 US$ or 18960.39 RSD/1 VASP-Cmax 1 mm reduction. Cost-effectiveness expressed through ICER showed significant reduction of PCA-IV morphine costs in the tDCS group. Further investigation of tDCS benefits with regards to reduction of postoperative pain treatment costs should also include the long-term benefits of reduced morphine use

Prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation in Serbian patients with Parkinson's disease

Background: Biomarkers of oxidative stress are relevant in the evaluation of the disease status and prooxidant-antioxidant balance, advanced oxidation protein products and lipid peroxidation products (malondialdehyde and 4-hydroxynonenal) are being extensively evaluated regarding their relationship with clinical presentation and disease severity.Aim of the study: The aim of this study was to evaluate the levels of the above-mentioned parameters in plasma of 39 men and 17 women with Parkinson's disease, originated from the Republic of Serbia and their relation to clinicopathological characteristics (gender, age at examination, duration of the disease, and Hoehn and Yahr score) and oxidative status.Results: The incidence of disease was 2:1 towards males. The investigated oxidative parameters were gender and Hoehn and Yahr related. Significant association of higher Hoehn and Yahr scores was observed for malondialdehyde (p = 0.01) and prooxidant-antioxidant balance (p = 0.02). Relation between oxidant-antioxidant status was further supported by observed positive correlation between 4-hydroxynonenal (p = 0.04) and prooxidant-antioxidant balance (p = 0.03). Finally, the multivariate analysis indicated that prooxidant-antioxidant balance and malondialdehyde were partially determined by gender (10.6% and 7.6%) and Hoehn and Yahr scores (13.6% and 18.8%), while Hoehn and Yahr scores contributed to the variance of advanced oxidation protein products with 13.2%.Conclusion: Our results indicate the higher level of oxidative stress (oxidant-antioxidant imbalance) and possible relation of several markers with gender and disease stage in patients with Parkinson's disease. The analyzed markers could be used to specify the severity of oxidative stress; however, their potential value should be analyzed in further studies.Peer-reviewed manuscript: [http://farfar.pharmacy.bg.ac.rs/handle/123456789/3420]Peer-reviewed manuscript: [http://farfar.pharmacy.bg.ac.rs/handle/123456789/3420

A Comprehensive Overview of Broca’s Aphasia after Ischemic Stroke

Aphasia denotes an acquired central disorder of language, which alters patient’s ability of understanding and/or producing spoken and written language. The main cause of aphasia is represented by ischemic stroke. The language disturbances are frequently combined into aphasic syndromes, contained in different vascular syndromes, which may suffer evolution/involution in the acute stage of ischemic stroke. The main determining factor of the vascular aphasia’s form is the infarct location. Broca’s aphasia is a non-fluent aphasia, comprising a wide range of symptoms (articulatory disturbances, paraphasias, agrammatism, anomia, and discrete comprehension disorders of spoken and written language) and is considered the third most common form of acute vascular aphasia, after global and Wernicke’s aphasia. It is caused by a lesion situated in the dominant cerebral hemisphere (the left one in right-handed persons), in those cortical regions vascularized by the superior division of the left middle cerebral artery (Broca’s area, the rolandic operculum, the insular cortex, subjacent white matter, centrum semiovale, the caudate nucleus head, the putamen, and the periventricular areas). The role of this chapter is to present the most important acquirements in the field of language and neurologic examination, diagnosis, and therapy of the patient with Broca’s aphasia secondary to ischemic stroke

Intermittent theta burst stimulation attenuates oxidative stress and reactive astrogliosis in the streptozotocin-induced model of Alzheimer’s disease-like pathology

IntroductionIntracerebroventricularly (icv) injected streptozotocin (STZ) is a widely used model for sporadic Alzheimer’s disease (sAD)-like pathology, marked by oxidative stress-mediated pathological progression. Intermittent theta burst stimulation (iTBS) is a noninvasive technique for brain activity stimulation with the ability to induce long-term potentiation-like plasticity and represents a promising treatment for several neurological diseases, including AD. The present study aims to investigate the effect of the iTBS protocol on the animal model of STZ-induced sAD-like pathology in the context of antioxidant, anti-inflammatory, and anti-amyloidogenic effects in the cortex, striatum, hippocampus, and cerebellum.MethodsMale Wistar rats were divided into four experimental groups: control (icv normal saline solution), STZ (icv STZ—3 mg/kg), STZ + iTBS (STZ rats subjected to iTBS protocol), and STZ + Placebo (STZ animals subjected to placebo iTBS noise artifact). Biochemical assays and immunofluorescence microscopy were used to evaluate functional and structural changes.ResultsThe icv STZ administration induces oxidative stress and attenuates antioxidative capacity in all examined brain regions. iTBS treatment significantly reduced oxidative and nitrosative stress parameters. Also, iTBS decreased Aβ-1-42 and APP levels. The iTBS enhances antioxidative capacity reported as elevated activity of its enzymatic and non-enzymatic components. In addition, iTBS elevated BDNF expression and attenuated STZ-induced astrogliosis confirmed by decreased GFAP+/VIM+/C3+ cell reactivity in the hippocampus.DiscussionOur results provide experimental evidence for the beneficial effects of the applied iTBS protocol in attenuating oxidative stress, increasing antioxidant capacity and decreasing reactive astrogliosis in STZ-administrated rats