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RSC Advances Jun 2024Multidrug-resistant bacteria resulting from the abuse and overuse of antibiotics have become a huge crisis in global public health security. Therefore, it is urgently...
Multidrug-resistant bacteria resulting from the abuse and overuse of antibiotics have become a huge crisis in global public health security. Therefore, it is urgently needed to develop new antibacterial drugs with unique mechanisms of action. As a versatile moiety, morpholine has been widely employed to enhance the potency of numerous bioactive molecules. In this study, a series of ruthenium-based antibacterial agents modified with the morpholine moiety were designed and characterized, aiming to obtain a promising metalloantibiotic with a multitarget mechanism. Antibacterial activity screening demonstrated that the most active complex Ru(ii)-3 exhibited the strongest potency against () with an MIC value of only 0.78 μg mL, which is better than most clinically used antibiotics. Notably, Ru(ii)-3 not only possessed excellent bactericidal efficacy, but could also overcome bacterial resistance. Importantly, Ru(ii)-3 very efficiently removed biofilms produced by bacteria, inhibited the secretion of bacterial exotoxins, and enhanced the activity of many existing antibiotics. The results of mechanism studies confirmed that Ru(ii)-3 could destroy the bacterial membrane and induce ROS production in bacteria. Furthermore, animal infection models confirmed that Ru(ii)-3 showed significant anti-infective activity . Overall, this work demonstrated that a morpholine-modified ruthenium-based agent is a promising antibiotic candidate in tackling the crisis of drug-resistant bacteria.
PubMed: 38915333
DOI: 10.1039/d4ra02667e -
Substance Abuse Treatment, Prevention,... Jun 2024The COTAT (Collaborative Opioid Taper After Trauma) Study was a randomized trial of an opioid taper support program using a physician assistant (PA) to provide pain and... (Randomized Controlled Trial)
Randomized Controlled Trial
The COTAT (Collaborative Opioid Taper After Trauma) Study was a randomized trial of an opioid taper support program using a physician assistant (PA) to provide pain and opioid treatment guidance to primary care providers assuming care for adult patients with moderate to severe trauma discharged from a Level I trauma center on opioid therapy. Patients were recruited, assessed, and randomized individually by a surgery research recruitment team one to two days prior to discharge to home. Participants randomized to the opioid taper support program were contacted by phone within a few days of discharge by the PA interventionist to confirm enrollment and their primary care provider (PCP). The intervention consisted of PA support as needed to the PCP concerning pain and opioid care at weeks 1, 2, 4, 8, 12, 16, and 20 after discharge or until the PCP office indicated they no longer needed support or the patient had tapered off opioids. The PA was supervised by a pain physician-psychiatrist, a family physician, and a trauma surgeon. Patients randomized to usual care received standard hospital discharge instructions and written information on managing opioid medications after discharge. Trial results were analyzed using repeated measures analysis. 37 participants were randomized to the intervention and 36 were randomized to usual care. The primary outcomes of the trial were pain, enjoyment, general activity (PEG score) and mean daily opioid dose at 3 and 6 months after hospital discharge. Treatment was unblinded but assessment was blinded. No significant differences in PEG or opioid outcomes were noted at either time point. Physical function at 3 and 6 months and pain interference at 6 months were significantly better in the usual care group. No significant harms of the intervention were noted. COVID-19 (corona virus 2019) limited recruitment of high-risk opioid tolerant subjects, and limited contact between the PA interventionist and the participants and the PCPs. Our opioid taper support program failed to improve opioid and pain outcomes, since both control and intervention groups tapered opioids and improved PEG scores after discharge. Future trials of post-trauma opioid taper support with populations at higher risk of persistent opioid use are needed. This trial is registered at clinicaltrials.gov under NCT04275258 19/02/2020. This trial was funded by a grant from the Centers for Disease Control and Prevention to the University of Washington Harborview Injury Prevention & Research Center (R49 CE003087, PI: Monica S. Vavilala, MD). The funder had no role in the analysis or interpretation of the data.
Topics: Humans; Male; Analgesics, Opioid; Female; Adult; Wounds and Injuries; Middle Aged; Hospitalization; Pain Management; Trauma Centers; Primary Health Care; Opioid-Related Disorders
PubMed: 38915106
DOI: 10.1186/s13011-024-00613-x -
Harm Reduction Journal Jun 2024The present commentary highlights the pressing need for systematic research to assess the implementation and effectiveness of medications for opioid use disorder, used...
BACKGROUND
The present commentary highlights the pressing need for systematic research to assess the implementation and effectiveness of medications for opioid use disorder, used in conjunction with peer recovery support services, to improve treatment outcomes for individuals with opioid use disorder in Central Appalachia. This region, encompassing West Virginia, Eastern Kentucky, Southwest Virginia, East Tennessee, and Western North Carolina, has long grappled with a disproportionate burden of the opioid crisis. Due to a complex interplay of cultural, socioeconomic, medical, and geographic factors, individuals in Central Appalachia face challenges in maintaining treatment and recovery efforts, leading to lower success rates.
APPROACH
To address the issue, we apply an exploratory approach, looking at the intersection of unique regional factors with the utilization of medications for opioid use disorder, in conjunction with peer recovery support services. This combined treatment strategy shows promise in addressing crucial needs in opioid use disorder treatment and enhancing the recovery journey. However, there are significant evidence gaps that need to be addressed to validate the expected value of incorporating peer support into this treatment strategy.
CONCLUSION
We identify nine obstacles and offer recommendations to address the gaps and advance peer recovery support services research. These recommendations include the establishment of specific partnerships and infrastructure for community-engaged, peer recovery support research; improved allocation of funding and resources to implement evidence-based practices such as peer support and medication-assisted treatment; developing a more precise definition of peer roles and their integration across the treatment and recovery spectrum; and proactive efforts to combat stigma through outreach and education.
Topics: Humans; Opioid-Related Disorders; Appalachian Region; Peer Group; Opioid Epidemic; Opiate Substitution Treatment; Social Support
PubMed: 38914988
DOI: 10.1186/s12954-024-01041-7 -
Military Psychology : the Official... Jul 2024Soldiers have high rates of substance use disorders (SUD), often in the aftermath of stressors experienced during military deployments. There are several factors that...
Soldiers have high rates of substance use disorders (SUD), often in the aftermath of stressors experienced during military deployments. There are several factors that protect against SUD. For example, individual factors like perceived resilience and group factors such as unit cohesion may make someone less likely to abuse substances. However, there is little research on the differential influence of these resilience factors on SUD over and above deployment stressors. In this study, we examined the relative effects of perceived resilience, unit cohesion, and deployment stressors on SUD in a sample of 21,449 active duty and reserve soldiers from the U.S. Army (primarily White and male, mean age = 28.66, SD = 7.41) using structural equation modeling. We found that unit cohesion (ß = -.17) and perceived resilience (ß = -.16) had negative effects on SUD over and above deployment stressors. The study findings clarify research on resilience to SUD and have implications for addressing substance use in the military, specifically regarding the importance of building unit cohesion.
Topics: Humans; Substance-Related Disorders; Male; Resilience, Psychological; Adult; Military Personnel; Female; Young Adult; Military Deployment; United States; Stress, Psychological
PubMed: 38913766
DOI: 10.1080/08995605.2023.2189861 -
PloS One 2024HIV, opioid use disorder (OUD), and mental health challenges share multiple syndemic risk factors. Each can be effectively treated with routine outpatient appointments,...
BACKGROUND
HIV, opioid use disorder (OUD), and mental health challenges share multiple syndemic risk factors. Each can be effectively treated with routine outpatient appointments, medication management, and psychosocial support, leading implementers to consider integrated screening and treatment for OUD and mental health in HIV care. Provider perspectives are crucial to understanding barriers and strategies for treatment integration.
METHODS
We conducted in-depth qualitative interviews with 21 HIV treatment providers and social services providers (12 individual interviews and 1 group interview with 9 participants) to understand the current landscape, goals, and priorities for integrated OUD, mental health, and HIV care. Providers were purposively recruited from known clinics in Mecklenburg County, North Carolina, U.S.A. Data were analyzed using applied thematic analysis in the NVivo 12 software program and evaluated for inter-coder agreement.
RESULTS
Participants viewed substance use and mental health challenges as prominent barriers to engagement in HIV care. However, few organizations have integrated structured screening for substance use and mental health into their standard of care. Even fewer screen for opioid use. Although medication assisted treatment (MAT) is effective for mitigating OUD, providers struggle to connect patients with MAT due to limited referral options, social barriers such as housing and food insecurity, overburdened staff, stigma, and lack of provider training. Providers believed there would be clear benefit to integrating OUD and mental health treatment in HIV care but lacked resources for implementation.
CONCLUSIONS
Integration of screening and treatment for substance use and mental health in HIV care could mitigate many current barriers to treatment for all three conditions. Efforts are needed to train HIV providers to provide MAT, expand resources, and implement best practices.
Topics: Humans; HIV Infections; Opioid-Related Disorders; Male; Female; Qualitative Research; Mass Screening; Adult; Mental Health; Middle Aged; Health Personnel; North Carolina
PubMed: 38913659
DOI: 10.1371/journal.pone.0305174 -
Annals of Surgery Open : Perspectives... Jun 2024Up to hundreds of billions of dollars are annually lost to fraud and abuse in the US health care, making it a significant burden on the system. This study investigates a...
Up to hundreds of billions of dollars are annually lost to fraud and abuse in the US health care, making it a significant burden on the system. This study investigates a specific instance of health care fraud in spine surgery, in which a medical device company ended up paying $75 million to settle violations of the False Claims Act. We review the surgical background regarding the kyphoplasty procedure, as well as its billing and reimbursement details. We also explore the official legal complaint brought by the US Department of Justice to tell the story of how one of the most significant medical innovations in spine surgery in the 21st century turned into a widespread fraudulent marketing scheme. In the sequence, we provide a detailed root cause analysis of this scandal and propose some proactive measures that can be taken to avoid such type of unfortunate events. Ultimately, this historical health care scandal constitutes a valuable lesson to surgeons, health care administrators, medical device companies, and policymakers on how misaligned incentives and subsequent unscrupulous practices can transform a medical innovation into an unfortunate tale of fraud and deceit.
PubMed: 38911625
DOI: 10.1097/AS9.0000000000000452 -
Cureus May 2024Corneal melt and perforation can arise from various etiologies, including the use of toxic topical drops, particularly topical non-steroidal anti-inflammatory drugs...
Corneal melt and perforation can arise from various etiologies, including the use of toxic topical drops, particularly topical non-steroidal anti-inflammatory drugs (NSAIDs). The literature has frequently documented the association between the use of topical NSAIDs and the subsequent development of corneal ulcers. More recently, reports have emerged linking the use of oral NSAIDs and colchicine to impaired corneal wound healing and corneal perforation. This case report presents an instance of corneal melting and subsequent perforation in a medically unburdened patient who had been self-administering oral NSAIDs for one year. The evidence presented in this report suggests a plausible association between the prolonged administration of oral NSAIDs and corneal melt. Consequently, healthcare practitioners should be mindful of this potential risk when considering the prolonged use of oral NSAIDs.
PubMed: 38910677
DOI: 10.7759/cureus.60853 -
Clinica Chimica Acta; International... Jun 2024The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids...
BACKGROUND AND AIMS
The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids with the sedative to reduce drug manufacturing costs and enhance their effects. In this study, we report the first fatality involving xylazine-adulterated heroin in the EU.
MATERIALS AND METHODS
The subject was a 33-year-old Caucasian male with a documented history of drug abuse who was found dead in a public area with puncture marks at the elbow. Peripheral blood and urine were collected at the autopsy and analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) after protein precipitation.
RESULTS
6-Monoacetylmorphine, total/free morphine, and codeine blood concentrations of 20.3, 236/105, and 38.3 ng/mL, respectively, indicated recent heroin consumption. Methadone blood concentration was below 10 ng/mL. Alprazolam, nordiazepam, and flurazepam blood concentrations were 23.9, 61.4, and 55.0 ng/mL, respectively. Benzoylecgonine blood concentration was below 5 ng/mL. Xylazine blood and urine concentrations were 105 and 72.6 ng/mL, respectively.
CONCLUSION
The combination of central nervous system depressants, i.e., opioids, benzodiazepines, and xylazine, was the principal cause of death by cardiorespiratory failure. The case was promptly reported to the UE Early Warning System on drugs.
PubMed: 38909977
DOI: 10.1016/j.cca.2024.119826 -
Nature Communications Jun 2024Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The...
Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats. Psilocin increased stimulus-independent PVN activity as measured by c-Fos expression in male and female rats. Psilocin increased PVN reactivity to an aversive air-puff stimulus in males but not females. Reactivity was restored at 2- and 7-days post-injection with no group differences. Additionally, prior psilocin injection did not affect PVN reactivity following acute restraint stress. Experimental groups sub-classified by baseline threat responding indicate that increased male PVN reactivity is driven by active threat responders. These findings identify the PVN as a significant site of psychedelic drug action with implications for threat responding behavior.
Topics: Animals; Paraventricular Hypothalamic Nucleus; Male; Psilocybin; Rats, Sprague-Dawley; Female; Rats; Hallucinogens; Proto-Oncogene Proteins c-fos; Behavior, Animal; Stress, Psychological
PubMed: 38909051
DOI: 10.1038/s41467-024-49741-9 -
Medicina 2024Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also...
Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also been an increase in the number of accidental and intentional overdoses that were treated by the health system. Its toxicity is dose-dependent and can cause fulminant liver failure, becoming one of the main reasons for liver transplantation in English-speaking countries. The case of a 28-year-old woman with a history of major depression and five previous suicide attempts, who deliberately ingested a significant amount of paracetamol tablets, is here presented. She developed fulminant liver failure and metabolic acidosis, for which she underwent an emergency liver transplant due to the severity of her condition, from which she evolved favorably. The decision to perform a liver transplant in serious cases like this and under a condition of severe psychiatric vulnerability is challenging and must be carefully considered. This particular case illustrates the importance of multidisciplinary care including psychiatric evaluation in patients with acetaminophen poisoning.
Topics: Humans; Acetaminophen; Female; Adult; Liver Transplantation; Liver Failure, Acute; Suicide, Attempted; Analgesics, Non-Narcotic; Drug Overdose
PubMed: 38907980
DOI: No ID Found