Spaceflight-associated pain.

PURPOSE OF REVIEW: Consequences of the expanding commercial spaceflight industry include an increase in total number of spaceflight participants and an accompanying surge in the average number of medical comorbidities compared with government-based astronaut corps. A sequela of these developments is an anticipated rise in acute and chronic pain concerns associated with spaceflight. This review will summarize diagnostic and therapeutic areas of interest that can support the comfort of humans in spaceflight. RECENT FINDINGS: Painful conditions that occur in space may be due to exposure to numerous stressors such as acceleration and vibration during launch, trauma associated with extravehicular activities, and morbidity resulting directly from weightlessness. Without normal gravitational forces and biomechanical stress, the hostile environment of space causes muscle atrophy, bone demineralization, joint stiffness, and spinal disc dysfunction, resulting in a myriad of pain generators. Repeated insults from abnormal environmental exposures are thought to contribute to the development of painful musculoskeletal and neuropathic conditions. SUMMARY: As humanity invests in Lunar and Martian exploration, understanding the painful conditions that will impede crew productivity and mission outcomes is critical. Preexisting pain and new-onset acute or chronic pain resulting from spaceflight will require countermeasures and treatments to mitigate long-term health effects.

Chronic pain for rheumatological disorders: Pathophysiology, therapeutics and evidence.

Pain is the leading reason people seek orthopedic and rheumatological care. By definition, most pain can be classified as nociceptive, or pain resulting from non-neural tissue injury or potential injury, with between 15% and 50% of individuals suffering from concomitant neuropathic pain or the newest category of pain, nociplastic pain, defined as "pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage, or of a disease or lesion affecting the somatosensory system." Pain classification is important because it affects treatment decisions at all levels of care. Although several instruments can assist with classifying treatment, physician designation is the reference standard. The appropriate treatment of pain should ideally involve multidisciplinary care including physical therapy, psychotherapy and integrative therapies when appropriate, and pharmacotherapy with non-steroidal anti-inflammatory drugs for acute, mechanical pain, membrane stabilizers for neuropathic and nociplastic pain, and serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants for all types of pain. For nonsurgical interventions, there is evidence to support a small effect for epidural steroid injections for an intermediate-term duration, and conflicting evidence for radiofrequency ablation to provide at least 6months of benefit for facet joint pain, knee osteoarthritis, and sacroiliac joint pain. Since pain and disability represent the top reason for elective surgery, it should be reserved for patients who fail conservative interventions. Risk factors for procedural failure are the same as risk factors for conservative treatment failure and include greater disease burden, psychopathology, opioid use, central sensitization and multiple comorbid pain conditions, poorly controlled preoperative and postoperative pain, and secondary gain.

A Method to Determine Capabilities and Resources for Spacecraft Medical Systems.

INTRODUCTION: This paper describes the method for assigning medical diagnostic and treatment capabilities and resources to the database which assists with an updated probabilistic risk analysis (PRA) tool for exploration class medical system planning. The National Aeronautics and Space Administration has used PRA since 2011 to inform mission medical system design, but existing tools are designed only for low Earth orbit. An updated PRA tool was needed to assist with exploration class missions.METHODS: A team of medical experts with a wide range of expertise and experience, including Space Medicine, was assembled to build capability and resource tables for the new PRA tool. This team met over 8 mo and used practice guidelines, literature, and experience to build capability and resource tables (CRTs) for each condition in the new PRA tool database.RESULTS: This process led to CRTs for each condition and a total of 617 distinct capabilities and 839 discrete resources.CONCLUSION: The CRT method is an effective way to translate medical practice guidelines into capabilities and resources usable by PRA tools for exploration class medical system planning. This same method may be used in commercial space ventures and in other applications in which medical predictive analytics are informative.Levin DR, Nelson AM, Zahner C, Stratton ER, Anderson A, Steller J. A method to determine capabilities and resources for spacecraft medical systems. Aerosp Med Hum Perform. 2024; 95(7):403-408.

Evaluation of Generative Language Models in Personalizing Medical Information: Instrument Validation Study.

BACKGROUND: Although uncertainties exist regarding implementation, artificial intelligence-driven generative language models (GLMs) have enormous potential in medicine. Deployment of GLMs could improve patient comprehension of clinical texts and improve low health literacy. OBJECTIVE: The goal of this study is to evaluate the potential of ChatGPT-3.5 and GPT-4 to tailor the complexity of medical information to patient-specific input education level, which is crucial if it is to serve as a tool in addressing low health literacy. METHODS: Input templates related to 2 prevalent chronic diseases-type II diabetes and hypertension-were designed. Each clinical vignette was adjusted for hypothetical patient education levels to evaluate output personalization. To assess the success of a GLM (GPT-3.5 and GPT-4) in tailoring output writing, the readability of pre- and posttransformation outputs were quantified using the Flesch reading ease score (FKRE) and the Flesch-Kincaid grade level (FKGL). RESULTS: Responses (n=80) were generated using GPT-3.5 and GPT-4 across 2 clinical vignettes. For GPT-3.5, FKRE means were 57.75 (SD 4.75), 51.28 (SD 5.14), 32.28 (SD 4.52), and 28.31 (SD 5.22) for 6th grade, 8th grade, high school, and bachelor's, respectively; FKGL mean scores were 9.08 (SD 0.90), 10.27 (SD 1.06), 13.4 (SD 0.80), and 13.74 (SD 1.18). GPT-3.5 only aligned with the prespecified education levels at the bachelor's degree. Conversely, GPT-4's FKRE mean scores were 74.54 (SD 2.6), 71.25 (SD 4.96), 47.61 (SD 6.13), and 13.71 (SD 5.77), with FKGL mean scores of 6.3 (SD 0.73), 6.7 (SD 1.11), 11.09 (SD 1.26), and 17.03 (SD 1.11) for the same respective education levels. GPT-4 met the target readability for all groups except the 6th-grade FKRE average. Both GLMs produced outputs with statistically significant differences (P<.001; 8th grade P<.001; high school P<.001; bachelors P=.003; FKGL: 6th grade P=.001; 8th grade P<.001; high school P<.001; bachelors P<.001) between mean FKRE and FKGL across input education levels. CONCLUSIONS: GLMs can change the structure and readability of medical text outputs according to input-specified education. However, GLMs categorize input education designation into 3 broad tiers of output readability: easy (6th and 8th grade), medium (high school), and difficult (bachelor's degree). This is the first result to suggest that there are broader boundaries in the success of GLMs in output text simplification. Future research must establish how GLMs can reliably personalize medical texts to prespecified education levels to enable a broader impact on health care literacy.

Literature review of spinal hematoma case reports: causes and outcomes in pediatric, obstetric, neuraxial and pain medicine cases.

BACKGROUND: The risk of spinal epidural hematoma (SEH) has been described in the literature but the impact in various patient populations has not been assessed in the same study. We identified the risk factors for SEH and calculated the OR for recovery in the pediatric, adult and obstetric (OB) patients based on the degree of neurological deficit before surgery. METHODS: Adult non-OB cases were categorized whether they were on anticoagulants or not; SEH was related to neuraxial or pain procedure; or whether there was adherence to the American Society of Regional Anesthesia (ASRA) guidelines. Eligible cases were identified through PubMed and Embase searches in the English literature from 1954 to July 2022. RESULTS: A total of 940 cases were evaluated. In the pediatric cases, SEH was typically spontaneous, related to coagulopathy or athletic trauma. OB cases were spontaneous or related to neuraxial injections. Among adults on anticoagulant(s), SEH was mostly spontaneous with no related etiology or related to neuraxial procedure. SEH occurred despite adherence to the ASRA guidelines. Among non-OB adults not on anticoagulants, SEH was due to trauma, neuraxial injections, surgery or other causes. Neurological recovery was related to the degree of neurological deficit before surgery. CONCLUSIONS: Our data show a preponderance of spontaneous SEH in all patient populations. SEH developed even though the ASRA guidelines were followed, especially in patients on multiple anticoagulants. Patients with less impairment prior to surgery had a higher likelihood of complete recovery, regardless of the interval between surgery and onset of symptoms.

Enhancing Standard of Care Chemotherapy Efficacy Using DNA-Dependent Protein Kinase (DNA-PK) Inhibition in Preclinical Models of Ewing Sarcoma.

Disruption of DNA damage repair via impaired homologous recombination is characteristic of Ewing sarcoma (EWS) cells. We hypothesize that this disruption results in increased reliance on nonhomologous end joining to repair DNA damage. In this study, we investigated if pharmacologic inhibition of the enzyme responsible for nonhomologous end joining, the DNA-PK holoenzyme, alters the response of EWS cells to genotoxic standard of care chemotherapy. We used analyses of cell viability and proliferation to investigate the effects of clinical DNA-PK inhibitors (DNA-PKi) in combination with six therapeutic or experimental agents for EWS. We performed calculations of synergy using the Loewe additivity model. Immunoblotting evaluated treatment effects on DNA-PK, DNA damage, and apoptosis. Flow cytometric analyses evaluated effects on cell cycle and fate. We used orthotopic xenograft models to interrogate tolerability, drug mechanism, and efficacy in vivo. DNA-PKi demonstrated on-target activity, reducing phosphorylated DNA-PK levels in EWS cells. DNA-PKi sensitized EWS cell lines to agents that function as topoisomerase 2 (TOP2) poisons and enhanced the DNA damage induced by TOP2 poisons. Nanomolar concentrations of single-agent TOP2 poisons induced G2M arrest and little apoptotic response while adding DNA-PKi-mediated apoptosis. In vivo, the combination of AZD7648 and etoposide had limited tolerability but resulted in enhanced DNA damage, apoptosis, and EWS tumor shrinkage. The combination of DNA-PKi with standard of care TOP2 poisons in EWS models is synergistic, enhances DNA damage and cell death, and may form the basis of a promising future therapeutic strategy for EWS.

Use of corticosteroids for adult chronic pain interventions: sympathetic and peripheral nerve blocks, trigger point injections - guidelines from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, the International Pain and Spine Intervention Society, and the North American Spine Society.

BACKGROUND: There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic-pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit. METHODS: Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed. RESULTS: This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections. CONCLUSIONS: In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions.