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The Journal of Pediatrics Jun 2024To determine whether an enteral, clonidine-based sedation strategy (CLON) during therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy (HIE) would decrease...
OBJECTIVE
To determine whether an enteral, clonidine-based sedation strategy (CLON) during therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy (HIE) would decrease opiate use, while maintaining similar short-term safety and efficacy profiles to a morphine-based strategy (MOR).
STUDY DESIGN
This was a single-center, observational study conducted at a level IV neonatal intensive care unit from January 1, 2017, to October 1, 2021. From April 13, 2020, to August 13, 2020, MOR was transitioning to CLON. Thus, patients receiving TH for HIE were grouped to MOR (before April 13, 2020) and CLON (after August 13, 2020). We calculated the total and rescue morphine milligram equivalent (MME)/ kg (primary outcome) and frequency of hemodynamic changes (secondary outcome) for both groups.
RESULTS
MOR and CLON groups (74 and 25 neonates, respectively) had similar baseline characteristics and need for rescue sedative intravenous infusion (21.6% MOR and 20% CLON). Both, MME/ kg and need for rescue opiates (combined bolus and infusions) were higher in MOR than CLON (p < 0.001). As days in TH advanced, a lower percentage of CLON patients needed rescue opiates (92% on day 1 to 68% on day 3). MOR patients received a higher cumulative dose of dopamine and more frequently required a second inotrope and hydrocortisone for hypotension. MOR had a lower respiratory rate during TH (p=0.01 vs. CLON).
CONCLUSIONS
Our CLON protocol is non-inferior to MOR, maintaining perceived effectiveness and hemodynamic safety, with an apparently reduced need for opiates and inotropes.
PubMed: 38889855
DOI: 10.1016/j.jpeds.2024.114158 -
JAMA Network Open Jun 2024Medications for opioid use disorder (MOUD) are an effective but underutilized treatment. Opioid use disorder prevalence is high among people receiving treatment in...
IMPORTANCE
Medications for opioid use disorder (MOUD) are an effective but underutilized treatment. Opioid use disorder prevalence is high among people receiving treatment in community outpatient mental health treatment facilities (MHTFs), but MHTFs are understudied as an MOUD access point.
OBJECTIVE
To quantify availability of MOUD at community outpatient MHTFs in high-burden states as well as characteristics associated with offering MOUD.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study performed a phone survey between April and July 2023 among a representative sample of community outpatient MHTFs within 20 states most affected by the opioid crisis, including all Certified Community Behavioral Health Centers (CCBHCs). Participants were staff at 450 surveyed community outpatient MHTFs in 20 states in the US.
MAIN OUTCOMES AND MEASURES
MOUD availability. A multivariable logistic regression was fit to assess associations of facility, county, and state-level characteristics with offering MOUD.
RESULTS
Surveys with staff from 450 community outpatient MHTFs (152 CCBHCs and 298 non-CCBHCs) in 20 states were analyzed. Weighted estimates found that 34% (95% CI, 29%-39%) of MHTFs offered MOUD in these states. Facility-level factors associated with increased odds of offering MOUD were: self-reporting being a CCBHC (odds ratio [OR], 2.11 [95% CI, 1.08-4.11]), providing integrated mental and substance use disorder treatment (OR, 5.21 [95% CI, 2.44-11.14), having a specialized treatment program for clients with co-occurring mental and substance use disorders (OR, 2.25 [95% CI, 1.14-4.43), offering housing services (OR, 2.54 [95% CI, 1.43-4.51]), and laboratory testing (OR, 2.15 [95% CI, 1.12-4.12]). Facilities that accepted state-financed health insurance plans other than Medicaid as a form of payment had increased odds of offering MOUD (OR, 1.95 [95% CI, 1.01-3.76]) and facilities that accepted state mental health agency funds had reduced odds (OR, 0.43 [95% CI, 0.19-0.99]).
CONCLUSIONS AND RELEVANCE
In this study of 450 community outpatient MHTFs in 20 high-burden states, approximately one-third offered MOUD. These results suggest that further study is needed to report MOUD uptake, either through increased prescribing at all clinics or through effective referral models.
Topics: Humans; Cross-Sectional Studies; Opioid-Related Disorders; United States; Health Services Accessibility; Community Mental Health Services; Female; Opiate Substitution Treatment; Male; Community Mental Health Centers; Adult; Analgesics, Opioid; Buprenorphine
PubMed: 38888921
DOI: 10.1001/jamanetworkopen.2024.17545 -
Immunity, Inflammation and Disease Jun 2024Ischemia-reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a...
INTRODUCTION
Ischemia-reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a crucial organ for carbohydrate and lipid metabolism, exhibits decreased tolerance to hepatic I/R in patients with diabetes mellitus (DM), resulting in a significant increase in hepatic dysfunction following surgery. This may be attributed to elevated oxidative stress and inflammation. Our prior research established sinomenine's (SIN) protective role against hepatic I/R injury. Nevertheless, the impact of SIN on hepatic I/R injury in DM rats remains unexplored.
OBJECTIVE AND METHODS
This study aimed to investigate the therapeutic potential of SIN in hepatic I/R injury in DM rats and elucidate its mechanism. Diabetic and hepatic I/R injury models were established in rats through high-fat/sugar diet, streptozotocin injection, and hepatic blood flow occlusion. Liver function, oxidative stress, inflammatory reaction, histopathology, and Nrf-2/HO-1 signaling pathway were evaluated by using UV spectrophotometry, biochemical assays, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, and Western blot analysis.
RESULTS
High-dose SIN (300 mg/kg) significantly attenuated hepatic I/R injury in DM rats, reducing serum activities of ALT and AST, decreasing the AST/ALT ratio, enhancing tissue contents of SOD and GSH-Px, suppressing the levels of TNF-α and IL-6, improving the liver histopathology, and activating Nrf-2/HO-1 signaling by promoting Nrf-2 trans-location from cytoplasm to nucleus. Low-dose SIN (100 mg/kg) was ineffective.
CONCLUSIONS
This study demonstrates that high-dose sinomenine's mitigates hepatic I/R-induced inflammation and oxidative stress in diabetes mellitus (DM) rats via Nrf-2/HO-1 activation, suggesting its potential as a preventive strategy for hepatic I/R injury in DM patients.
Topics: Animals; Oxidative Stress; Morphinans; Rats; Diabetes Mellitus, Experimental; Reperfusion Injury; Male; Liver; Rats, Sprague-Dawley; Inflammation; NF-E2-Related Factor 2; Signal Transduction
PubMed: 38888355
DOI: 10.1002/iid3.1271 -
European Heart Journal. Case Reports Apr 2024Tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) inhibitor pathway with immune checkpoint blockade have shown promising outcomes in...
Acute aortic catastrophe caused by cardiovascular oncological manipulation by tyrosine kinase inhibitors with immune checkpoint blockades: a case report and literature review.
BACKGROUND
Tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) inhibitor pathway with immune checkpoint blockade have shown promising outcomes in managing metastatic renal cancer. However, they increase the risk of a person developing high blood pressure and cardiovascular complications.
CASE SUMMARY
In this study, we report the case of a 73-year-old woman on axitinib and pembrolizumab for her Stage 4 renal cell carcinoma. She presented with intractable chest pain and high systolic blood pressure, not responding to opiates. Her computed tomography angiography results showed an acute intra-mural haematoma with a rupture in the descending thoracic aorta. She underwent emergency thoracic endovascular aortic repair. Post-operatively, she recovered fully without any neurological or cardiovascular issues.
DISCUSSION
The severity of cardiovascular haemodynamic complications arising from the consumption of VEGF inhibitors and from immunotherapy and the lack of anti-hypertensive strategies to adequately manage such events require an unequivocal and urgent assessment of their cardiovascular safety. This case highlights the crucial role of cardiovascular oncology in managing such acute aortic catastrophes.
PubMed: 38887778
DOI: 10.1093/ehjcr/ytae169 -
Addiction Science & Clinical Practice Jun 2024Buprenorphine is an effective and safe treatment for opioid use disorder, but the requirement for moderate opioid withdrawal symptoms to emerge prior to initiation is a...
BACKGROUND
Buprenorphine is an effective and safe treatment for opioid use disorder, but the requirement for moderate opioid withdrawal symptoms to emerge prior to initiation is a significant treatment barrier.
CASE PRESENTATION
We report on two cases of hospitalized patients with severe, active opioid use disorder, in which we initiated treatment with transdermal buprenorphine over 48 h, followed by the administration of a single dose of sublingual buprenorphine/naloxone and then extended-release subcutaneous buprenorphine. The patients did not experience precipitated withdrawal and only had mild withdrawal symptoms.
CONCLUSIONS
This provides preliminary evidence for a rapid induction strategy that may improve tolerability, caregiver burden, and treatment retention as compared to previous induction strategies.
Topics: Humans; Opioid-Related Disorders; Buprenorphine; Delayed-Action Preparations; Administration, Cutaneous; Male; Adult; Substance Withdrawal Syndrome; Narcotic Antagonists; Female; Opiate Substitution Treatment; Injections, Subcutaneous; Middle Aged; Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination
PubMed: 38886826
DOI: 10.1186/s13722-024-00479-1 -
Swiss Medical Weekly Jun 2024In Switzerland, a cantonal authorisation is required to introduce opioid agonist treatments (OAT). We investigated and compared the terms of these cantonal OAT...
BACKGROUND AND AIM
In Switzerland, a cantonal authorisation is required to introduce opioid agonist treatments (OAT). We investigated and compared the terms of these cantonal OAT authorisations throughout Switzerland. The primary objective was to determine how the overseeing cantonal officials implemented and perceived the legal requirements.
METHOD
We started with a cross-sectional analysis of legal texts and cantonal OAT guidelines. Based on the document analysis, we conducted 26 semi-structured interviews with the cantonal officials who grant OAT authorisations.
FINDINGS
In most cantons (21 of 25), the OAT authorisation is specific to the person treated and must be renewed every year. Today, 21 cantons either have implemented or are implementing the same web-based software to process and manage OAT authorisation requests. Cantons have implemented diverging requirements regarding, amongst others, the involvement of third parties in OAT and the training required of prescribing physicians. Lastly, the OAT process does not seem to be a high priority for the overseeing officials.
CONCLUSIONS
From a legal standpoint, OAT authorisations should be straightforward, yet we found significant divergences among cantonal systems. We could not find scientific evidence that supports a given framework. We recommend harmonizing the 26 cantonal systems while reviewing the need for OAT authorisation.
Topics: Humans; Switzerland; Cross-Sectional Studies; Analgesics, Opioid; Qualitative Research; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 38885521
DOI: 10.57187/s.3629 -
PloS One 2024The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use... (Randomized Controlled Trial)
Randomized Controlled Trial
The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use disorder (OUD) at 6 months post-release. Three randomized trials (combined N = 330) were combined to assess whether MOUD (extended-release naltrexone or interim methadone) initiated prior to release from jail with or without PN would reduce the likelihood of a DSM-5 diagnosis of OUD 6 months post-release relative to enhanced treatment-as-usual (ETAU). Across the three studies, assignment to MOUD compared to ETAU was not associated with an OUD diagnosis at 6 months post-release (69% vs. 75%, respectively, OR = 0.67, 95% CI: 0.42 to 1.20). Similarly, PN compared to MOUD without PN was not associated with an OUD diagnosis (63% vs 77%, respectively, OR = 0.61, 95% CI: 0.27 to 1.53). Results underscore the need to further optimize the effectiveness of MOUD for patients initiating treatment in jail, beginning with an emphasis on post-release treatment adherence.
Topics: Humans; Opioid-Related Disorders; Male; Naltrexone; Female; Adult; Methadone; Jails; Opiate Substitution Treatment; Middle Aged; Narcotic Antagonists; Prisoners
PubMed: 38885220
DOI: 10.1371/journal.pone.0305165 -
BioRxiv : the Preprint Server For... Sep 2023After injury, mammalian spinal cords develop scars to seal off the damaged area and prevent further injury. However, excessive scarring can hinder neural regeneration...
After injury, mammalian spinal cords develop scars to seal off the damaged area and prevent further injury. However, excessive scarring can hinder neural regeneration and functional recovery (1, 2). These competing actions underscore the importance of developing therapeutic strategies to dynamically modulate the extent of scar formation. Previous research on scar formation has primarily focused on the role of astrocytes, but recent evidence suggests that ependymal cells also participate. Ependymal cells normally form the epithelial layer encasing the central canal, but they undergo massive proliferation and differentiation into astroglia following certain types of injury, becoming a core component of scars (3-7). However, the mechanisms regulating ependymal proliferation in both healthy and injured conditions remain unclear. Here, we uncover an intercellular kappa (κ) opioid signaling pathway that controls endogenous ependymal proliferation. Specifically, we detect expression of the κ opioid receptor, OPRK1, in a functionally under-characterized cell type called cerebrospinal fluid-contacting neurons (CSF-cNs). We also discover a neighboring cell population that express the cognate ligand, prodynorphin (PDYN). Importantly, OPRK1 activation excites CSF-cNs, and systemic administration of a κ antagonist enhances ependymal proliferation in uninjured spinal cords in a CSF-cN-dependent manner. Moreover, injecting a κ agonist reduces the proliferation induced by dorsal hemisection. Altogether, our data suggest a regulatory mechanism whereby PDYN cells tonically release κ opioids to stimulate CSF-cNs, which in turn suppress ependymal proliferation. This endogenous pathway provides a mechanistic basis for the potential use of κ opiates in modulating scar formation and treating spinal cord injuries.
PubMed: 38883735
DOI: 10.1101/2023.09.07.556726 -
The Korean Journal of Pain Jun 2024Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to...
BACKGROUND
Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. Biguanide-type drugs such as metformin (MET) are effective for neuroprotection and can be beneficial for addressing opioid tolerance in the treatment of chronic pain. It has been proposed that analgesic tolerance to NSAIDs is mediated by the endogenous opioid system. According to the cross-tolerance between NSAIDs, especially sodium salicylate (SS), and opiates, especially morphine, the objective of this study was to investigate whether MET administration can reduce tolerance to the anti-nociceptive effects of SS.
METHODS
Fifty-six male Wistar rats were used in this research (weight 200-250 g). For induction of tolerance, SS (300 mg/kg) was injected intraperitoneally for 7 days. During the examination period, animals received MET at doses of 50, 75, or 100 mg/kg for 7 days to evaluate the development of tolerance to the analgesic effect of SS. The hot plate test was used to evaluate the drugs' anti-nociceptive properties.
RESULTS
Salicylate injection significantly increased hot plate latency as compared to the control group, but the total analgesic effect of co-treatment with SS + Met50 was stronger than the SS group. Furthermore, the effect of this combination undergoes less analgesic tolerance over time.
CONCLUSIONS
It can be concluded that MET can reduce the analgesic tolerance that is induced by repeated intraperitoneal injections of SS in Wister rats.
PubMed: 38881281
DOI: 10.3344/kjp.24066 -
The Journal of Adolescent Health :... Jul 2024
Topics: Humans; Buprenorphine; Opioid-Related Disorders; Adolescent; Opiate Substitution Treatment; Health Services Accessibility; Narcotic Antagonists; Injections
PubMed: 38880557
DOI: 10.1016/j.jadohealth.2024.04.010