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Neuropharmacology Sep 2023This Special Issue of Neuropharmacology on psychedelics provides a timely and comprehensive update on progress following the previous Neuropharmacology Special Issue...
This Special Issue of Neuropharmacology on psychedelics provides a timely and comprehensive update on progress following the previous Neuropharmacology Special Issue "Psychedelics: New Doors, Altered Perceptions". Remarkable advances have been made in basic and clinical research on psychedelics in the five years since 2018. It is partly based on the seminar series focused on psilocybin organized by the National Institutes of Health (NIH), USA from April to June 2021, the "NIH Psilocybin Research Speaker Series". Participants were world leading experts, including scientists, medical practitioners, clinical psychologists and oncologists, and attendees from additional disciplines of patient advocacy, law, government science policy and regulatory policy. To provide a global perspective, their contributions are complemented with reviews by some of the world's most eminent scientists in the field. The US Food and Drug Administration (FDA) has granted two breakthrough therapy designations for psilocybin in treatment resistant depression (TRD) in 2018 and major depressive disorder (MDD) in 2019, as well as for MDMA for the treatment of post-traumatic stress disorder (PTSD) in 2017. Clinical trials are in progress to assess the therapeutic value of psilocybin in MDD and TRD, and in other indications such as cancer-related anxiety and depression, anorexia, PTSD, substance use disorders and various types of chronic pain. The contributors' insights should assist basic and applied science for transition of psychedelics from bench to potential mainstream therapies. The implications are global, because FDA approval of these new medicines will increase international interest and efforts.
Topics: Humans; Hallucinogens; Psilocybin; Depressive Disorder, Major; Substance-Related Disorders; Anxiety
PubMed: 37247807
DOI: 10.1016/j.neuropharm.2023.109610 -
Journal of Blood Medicine 2023Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, acquired clonal abnormality, which renders hematopoietic cells exquisitely sensitive to complement-mediated... (Review)
Review
Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, acquired clonal abnormality, which renders hematopoietic cells exquisitely sensitive to complement-mediated destruction. Classical features of PNH include intravascular hemolytic anemia, increased thrombotic risk, and manifestations related to end-organ damage (eg fatigue, chest pain, dyspnea, renal failure, and pulmonary hypertension). With supportive care alone, mortality rate of patients with PNH is approximately 35%. The anti-C5 monoclonal antibody, eculizumab, was the first targeted therapy approved for PNH, and led to improved hemoglobin, quality of life, reduced transfusion need, reduced thrombosis, and greater overall survival. More recently, therapeutics such as longer acting anti-C5 (ravulizumab) and anti-C3 (pegcetacoplan) medications have been approved, along with other novel therapeutics in late-stage clinical trials. Biosimilars of eculizumab are also now available. Proximal inhibitors (against C3, factor B, and factor D) have shown significant improvements in hemoglobin and transfusion-avoidance in patients who remain anemic despite C5 inhibition. Despite these novel therapies, some unmet challenges remain, including management of breakthrough hemolysis, clinically significant iatrogenic extravascular hemolysis, optimal management in pregnancy, and infection risk mitigation as new targets in the complement system are blocked. In addition, the use of self-administered subcutaneous and oral therapies raises concerns around treatment adherence and the risks of uncontrolled terminal complement. Given the ultra-rare nature of PNH, development is underway of a centralized international registry to capture and analyze the data as they mature for various new therapies and characterize the clinical challenges related to PNH management.
PubMed: 38084255
DOI: 10.2147/JBM.S431493 -
Frontiers in Pain Research (Lausanne,... 2023
PubMed: 37521942
DOI: 10.3389/fpain.2023.1236538 -
Journal of Anesthesia, Analgesia and... Jul 2023Breakthrough cancer pain (BTcP) is a complex and variegate phenomenon that may change its presentation during the course of patients' disease in the same individual. An... (Review)
Review
Breakthrough cancer pain (BTcP) is a complex and variegate phenomenon that may change its presentation during the course of patients' disease in the same individual. An appropriate assessment is fundamental for depicting the pattern of BTcP. This information is determinant for a personalized management of BTcP. The use of opioids as needed is recommended for the management of BTcP. There are several options which should be chosen according to the individual pattern of BTcP. In general, a drug with a short onset and offset should be preferred. Although oral opioids may still have specific indications, fentanyl products have been found to be more rapid and effective. The most controversial point regards the opioid dose to be used. The presence of opioid tolerance suggests to use a dose proportional to the dose used for background analgesia. In contrast, regulatory studies have suggested to use the minimal available dose to be titrated until the effective dose. Further large studies should definitely settle this never ended question.
PubMed: 37480136
DOI: 10.1186/s44158-023-00101-x -
Current Oncology (Toronto, Ont.) Nov 2023Cancer pain intensity (PI) fluctuates, but the relationship between pain flares and background pain with respect to pain management is not settled. We studied how flare...
Cancer pain intensity (PI) fluctuates, but the relationship between pain flares and background pain with respect to pain management is not settled. We studied how flare and background PIs corresponded with treatment results for background cancer pain. Patients admitted to an acute palliative care unit with average and/or worst PI ≥ 1 on the 11-point numeric rating scale were included. Average and worst PI at admission and average PI at discharge were collected. We examined how the difference and ratio between worst and average PI and average PI at admission, were associated with average PI development during hospitalization. Positive differences between worst and average PI at admission were defined as pain flares. Ninety out of 131 patients had pain flares. The reduction in average PI for patients with flares was 0.9 and for those without, 1.9 ( = 0.02). Patients with large worst minus average PI differences reported the least improvement, as did those with large worst/average PI ratios. Patients with pain flares and average PI ≤ 4 at admission had unchanged average PI during hospitalization, while those with pain flares and average PI > 4 experienced pain reduction (2.1, < 0.001). Large pain flares, in absolute values and compared to background PI, were associated with inferior pain relief.
Topics: Humans; Palliative Care; Cancer Pain; Pain; Neoplasms; Pain Management
PubMed: 38132380
DOI: 10.3390/curroncol30120746 -
Biomedicines Mar 2024Diabetic neuropathic pain (DNP) is one of the common and severe late-stage complications of diabetes mellitus, which could greatly influence the patients' quality of... (Review)
Review
Diabetic neuropathic pain (DNP) is one of the common and severe late-stage complications of diabetes mellitus, which could greatly influence the patients' quality of life. Patients with DNP often experience spontaneous pain and evoked pain such as mechanical allodynia and thermal hyperalgesia, meaning that their physical and psychological health are severely impaired. Unfortunately, the mechanisms of DNP remain highly elusive, so substantial breakthrough in effective DNP targeted treatments is still clinically challenging. This article will hence summarise the main mechanisms currently known to underlie DNP pathogenesis, along with describing some of the current and potential treatment methods against diabetic neuropathic pain.
PubMed: 38540203
DOI: 10.3390/biomedicines12030589