Corrigendum: Case Series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequalae of COVID (PASC).

[This corrects the article DOI: 10.3389/fmed.2023.1122529.].

Case series: Maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC).

Post-acute sequelae of COVID (PASC), or long COVID, is a multisystem complication of SARS-CoV-2 infection that continues to debilitate millions worldwide thus highlighting the public health importance of identifying effective therapeutics to alleviate this illness. One explanation behind PASC may be attributed to the recent discovery of persistent S1 protein subunit of SARS-CoV-2 in CD16+ monocytes up to 15 months after infection. CD16+ monocytes, which express both CCR5 and fractalkine receptors (CX3CR1), play a role in vascular homeostasis and endothelial immune surveillance. We propose targeting these receptors using the CCR5 antagonist, maraviroc, along with pravastatin, a fractalkine inhibitor, could disrupt the monocytic-endothelial-platelet axis that may be central to the etiology of PASC. Using five validated clinical scales (NYHA, MRC Dyspnea, COMPASS-31, modified Rankin, and Fatigue Severity Score) to measure 18 participants' response to treatment, we observed significant clinical improvement in 6 to 12 weeks on a combination of maraviroc 300 mg per oral twice a day and pravastatin 10 mg per oral daily. Subjective neurological, autonomic, respiratory, cardiac and fatigue symptoms scores all decreased which correlated with statistically significant decreases in vascular markers sCD40L and VEGF. These findings suggest that by interrupting the monocytic-endothelial-platelet axis, maraviroc and pravastatin may restore the immune dysregulation observed in PASC and could be potential therapeutic options. This sets the framework for a future double-blinded, placebo-controlled randomized trial to further investigate the drug efficacy of maraviroc and pravastatin in treating PASC.

Remdesivir-Induced Extreme Sinus Bradycardia in COVID-19.

During the COVID-19 pandemic, there was an urgent need for any medication to help reduce the high death rate experienced during this deadly surge. Remdesivir is an FDA-approved drug for COVID-19 treatment, given its anti-inflammatory properties. Upon extensive literature search, we found two studies and four cases of COVID-19-induced pneumonia treated with remdesivir who were developing bradycardia. In most of these cases, the bradycardia resolved within one-to-two days of holding remdesivir, which correlated with the half-life of remdesivir. Remdesivir was shown to have benefits in COVID-19-induced pneumonia during the COVID-19 surge; however, its use has been controversial. According to the studies, the sinus bradycardia following remdesivir administration does not impact patients' prognosis in terms of ICU admission and in-hospital mortality. There are multiple case reports noted to report several remdesivir-induced cardiac side effects. In our case, prolonged use and high dosages may induce cardiotoxicity, manifesting as severe bradycardia. Several possible mechanisms for cardiac adverse effects with remdesivir need further investigation and research as COVID-19 remains an active global issue. We present a 53-year-old man hospitalized with COVID-19-induced pneumonia who experienced extreme sinus bradycardia that is likely attributable to remdesivir.

Development of a bedside pain assessment kit for the classification of patients with osteoarthritis.

There are no standardized bedside assessments for subtyping patients with osteoarthritis (OA) based on pain mechanisms. Thus, we developed a bedside sensory testing kit (BSTK) to classify OA patients based on sensory profiles potentially indicative of pain mechanism. After usability and informal reliability testing (n = 22), the kit was tested in a formal reliability study (n = 20). Patients completed questionnaires and sensory testing: pressure algometry to detect hyperalgesia; repeat algometry after heterotopic noxious conditioning stimulation to measure diffuse noxious inhibitory control (DNIC); light touch using Von Frey filaments; and cold allodynia using a brass rod. The procedure was brief and well tolerated. Algometry and filament testing were highly reliable [intra-class correlation coefficients (ICCs) 0.71-0.91]; DNIC was acceptably reliable (ICCs 0.53-0.91); brass rod reliability was inconclusive. Patients were classified empirically into four groups: "All abnormal findings" (primary and secondary hyperalgesia and dysfunctional DNIC); "all normal findings"; and two intermediate groups. The "all abnormal findings" group had more neuropathic pain symptoms, and lower WOMAC total, stiffness, and activity scores than the "all normal findings" group. Simple BSTK procedures, consolidated in a kit, reliably classified OA patients into subgroups based on sensory profile, suggesting that OA patients differ in underlying pain mechanisms. Further research is needed to confirm these subgroups and determine their validity in predicting response to treatment.

Starvation marrow - gelatinous transformation of bone marrow.

Gelatinous bone marrow transformation (GMT), also known as starvation marrow, represents a rare pathological entity of unclear etiology, in which bone marrow histopathology demonstrates hypoplasia, fat atrophy, and gelatinous infiltration. The finding of gelatinous marrow transformation lacks disease specificity; rather, it is an indicator of severe illness and a marker of poor nutritional status, found in patients with eating disorders, acute febrile illnesses, acquired immunodeficiency syndrome, alcoholism, malignancies, and congestive heart failure. We present a middle-aged woman with a history of alcoholism, depression, and anorexia nervosa who presented with failure to thrive and macrocytic anemia, with bone marrow examination demonstrative of gelatinous transformation, all of which resolved with appropriate treatment. To our knowledge, there are very few cases of GMT which have been successfully treated; thus, our case highlights the importance of proper supportive management.

A brief survey to characterize oxycodone abuse patterns in adolescents enrolled in two substance abuse recovery high schools.

BACKGROUND: Although oxycodone is one of the most widely available and abused opioids, little published information exists on the abuse of immediate-release oxycodone. OBJECTIVE: To obtain information on abuse of oxycodone and the effectiveness of abuse-deterrent strategies, especially for immediate-release oxycodone, we surveyed oxycodone abuse patterns in a population of experienced opioid abusers. METHODS: Students or recent graduates of two substance abuse recovery high schools in Massachusetts were surveyed on abuse behaviors with short-acting single-entity oxycodone (e.g., Roxicodone), short-acting combination oxycodone (e.g., Percocet), and extended-release oxycodone. RESULTS: Twenty-four students completed surveys. Mean age was 17.7 years (range 16-19), and mean age at first abuse of oxycodone was 15 (range 13-18). Overall, 56% of students reported oxycodone as their favorite prescription opioid to abuse. The primary preferred method of abuse of all oxycodone formulations was intranasal administration: 83% of single-entity oxycodone abusers preferred intranasal administration compared with 67% of combination oxycodone abusers and 69% of extended-release oxycodone abusers. Approximately half of our respondents preferred to ingest oxycodone orally, 25-38% of respondents swallowed the pill intact, and another 13-17% chewed the pill before swallowing. Maximum dose ever abused at one time ranged from 15 to 400 mg. Most respondents had abused ≥60 mg of oxycodone at a time. CONCLUSIONS: In this small study, adolescent oxycodone abusers use high quantities of oxycodone at a time, alter routes of administration for not only extended-release but also immediate-release products, and commonly abuse single-entity oxycodone products. Abuse-deterrent formulations may be one strategy for addressing such behaviors.

Tampering with prescription opioids: nature and extent of the problem, health consequences, and solutions.

BACKGROUND: Transdermal and solid oral prescription opioid (PO) formulations can be abused by ingesting (with or without tampering), snorting, or injection (both requiring tampering). OBJECTIVE: To determine the patterns of tampering with POs for abuse. METHODS: Information was collected from published studies and databases. RESULTS: Tampering with POs for abuse is common practice. Ingestion is the most prevalent method of abuse, followed by snorting and injection. From 1992 to 2002, injecting POs has decreased in favor of ingesting and snorting. Methods of abuse vary widely by product. Abuse methods with the highest morbidity are injection and inhalation. CONCLUSIONS: The seriousness of health outcomes associated with tampering with POs warrants the development of PO formulations that prevent or deter tampering.

Retrospective accounts of initial subjective effects of opioids in patients treated for pain who do or do not develop opioid addiction: a pilot case-control study.

This pilot case-control study retrospectively assessed between-groups differences in subjective opioid effects in patients treated for the first time with opioids for chronic pain. Cases were individuals in an inpatient substance abuse treatment center for primary prescription opioid addiction whose initial exposure to prescription opioids was reported for chronic pain. Controls had not developed prescription opioid addiction as measured in part by close monitoring on long-term opioid therapy at a pain management center. Twenty subjects in each group completed a battery of measures to capture data related to the individual's first exposure to prescription opioids. The Morphine Benzedrine Group subscale of an adapted 49-item Addiction Center Research Inventory (ARCI), designed to measure euphoria and other drug effects, showed an average score of 8.70 (+/-4.18) in cases versus 2.55 (+/-3.36) in controls (p<0.001), indicating a significantly greater "euphoric" effect of opioids in the cases compared to the controls. Differences in the subjective response to opioids suggest that: (1) a subgroup of patients does develop euphoria when taking opioids for pain, which may be a risk factor for eventual development of prescription opioid addiction; and (2) subjective effects predictive of eventual addiction may include stimulation and other experiences not typically associated with opioids.