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1.
Wideochir Inne Tech Maloinwazyjne ; 19(1): 25-31, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38974756

RESUMO

Introduction: A meta-analysis was performed to examine the effects of wound catheter (WC) local anaesthetic infiltration (LAI) and epidural analgesia (EA) in open hepatectomy (OH). Material and methods: A systematic literature review was performed, which found 350 subjects with OH at the baseline of the studies; 159 of them were treated with WC local anaesthetic infiltration, and 191 used EA. Results: WC LAI substantially reduced the functional recovery time (MD = -0.64; 95% CI, -1.02 to -0.26, p < 0.001) and increased the pain score on the second postoperative day (MD = 0.25; 95% CI: 0.10-0.40, p < 0.001) compared to EA in OH patients. WC LAI did not vary from EA in OH patients in second postoperative opiate use (MD = -14.86; 95% CI: -32.88 to 3.16, p = 0.11) or overall complication rate (OR = 0.66; 95% CI: 0.41-1.04, p = 0.07). Conclusions: WC LAI showed a non-significant difference in opiate consumption on the second postoperative day and in the overall complication rate, compared with EA, but it showed a lower functional recovery time and higher pain score.

2.
HCA Healthc J Med ; 5(2): 87-95, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984234

RESUMO

Background: The purpose of the study was to investigate the relationship between community-level variables and emergency department (ED) visit rates before and during COVID-19. The focus was on opioid-related ED visits. Despite large declines in overall ED visits during COVID-19, opioid-related visits increased. While visits for avoidable conditions decreased, the opposite was true for opioid-related visits. Methods: We combined data from Florida EDs with community-level variables from the 2020 American Community Survey. The outcome measures of the study were quarterly ZIP code tabulation-area-level ED visit rates for opioid-related ED visits as well as visit rates for all other causes. Associations with opioid-related visit rates were estimated before and during COVID-19. Results: The associations between community-level variables and opioid-related visit rates did not match those found when analyzing overall ED visit rates. The increase in opioid-related visits during COVID-19 was not unique to or more prevalent in areas with a larger percentage of racial/ethnic minority populations. However, socioeconomic status was important, as areas with higher unemployment, lower income, lower home ownership, and higher uninsured had higher overall ED visit rates and opioid visit rates during the pandemic. In addition, the negative association with income increased during the pandemic. Conclusion: These results suggest socioeconomic status should be the focus of prevention and treatment efforts to reduce opioid-related visits in future pandemics. Healthcare organizations can use these results to target their prevention and treatment efforts during future pandemics.

3.
Forensic Sci Int ; 361: 112130, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38986227

RESUMO

Loperamide, a potent µ-opioid receptor agonist used as an antidiarrheal drug, exhibits increased bioavailability at supratherapeutic doses, causing potential central nervous system effects. Its misuse for opioid withdrawal relief and euphoria can lead to dangerously elevated blood levels, causing severe cardiac dysrhythmias and death. This study aimed to compare loperamide positive autopsy cases in Sweden and Finland after the introduction of postmortem toxicological analysis of loperamide, focusing on loperamide's role in fatalities and identifying common characteristics among those affected. All cases with detected loperamide in femoral blood at forensic autopsies in Sweden (2012-2022) and Finland (2017-2022) were included. In Sweden, loperamide was detected in 126 individuals, and in Finland, in 111 individuals. The incidence of individuals positive for loperamide in postmortem femoral blood increased steadily over the study duration in both Sweden and Finland. Loperamide related fatalities were observed exclusively in Sweden (n=80), predominantly involving younger males with histories of substance abuse, typically classified as accidental deaths. The group of loperamide nonrelated deaths in Sweden mirrored the entirety of cases in Finland. The concentration of loperamide in postmortem femoral blood was significantly higher in cases where loperamide was considered the cause of death (median 0.140 µg/g) compared to cases where loperamide contributed (median 0.080 µg/g), as well as in deaths unrelated to loperamide in both countries (Sweden: median 0.029 µg/g; Finland: median 0.010 µg/ml). The high limit of quantification for loperamide in Sweden may underestimate therapeutic users in epidemiological assessments. This study underscores the absence of loperamide misuse in Finland and indicates a rising trend of loperamide abuse in Sweden.

4.
J Emerg Nurs ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39001772

RESUMO

INTRODUCTION: Opioid-related events continue to claim lives in the United States at alarming rates. Naloxone-dispensing rates fall dramatically short of national expectations. Emergency registered nurses are uniquely poised to connect at-risk patients with naloxone resources. This study sought to (1) describe the emergency registered nurses' willingness to provide naloxone resources and (2) explore variables that may influence the nurse's willingness to provide resources. METHODS: A cross-sectional, survey-based design was deployed using an online branch logic approach to include a national sample of emergency registered nurses. The Willingness to Provide, a validated questionnaire, measured the registered nurse's willingness to provide naloxone resources for patients at risk of opioid overdose. Eight variables were assessed for potential influence on willingness. RESULTS: A total of 159 nurses from 32 states and the District of Columbia completed the online survey via the Research Electronic Data Capture platform. The results revealed a mean Willingness to Provide score of 38.64 indicating a willingness to provide naloxone resources. A statistically significant relationship was identified between the nurse's willingness and years of nursing experience (P = .001), knowledge (P = .015), desire (P = .001), and responsibility (P < .001). DISCUSSION: In this representative sample, emergency nurses are willing to provide naloxone resources; furthermore, results indicate that higher knowledge, desire, and responsibility scores increase the nurse's willingness to provide naloxone resources; with education and clear expectations, emergency nurses may be able to improve the connection of patients at risk of opioid overdose with naloxone, a potentially lifesaving connection.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39016435

RESUMO

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To evaluate the impact of a best-practice advisory (BPA) and South Carolina legislation on naloxone prescribing patterns. The primary objective was to assess the change in naloxone prescription rates following BPA implementation. The secondary objective was to analyze the performance of the BPA. METHODS: Naloxone prescriptions generated before (July 28, 2020, through July 27, 2021) and after (July 28, 2021, through July 28, 2022) BPA implementation were analyzed via retrospective chart review. Lists of patients at risk for opioid overdose and patients for whom the BPA fired were generated for March 2022. The BPA's effectiveness was evaluated based on the proportion of at-risk patients missed by the alert, the frequency with which the BPA resulted in a naloxone prescription, and the reasons for not prescribing naloxone when the BPA fired. RESULTS: Following BPA implementation, there was a significant increase in the average monthly naloxone prescribing rate from 66.1 to 625.5 prescriptions per month. Overall, 2,086 patients were considered at risk for opioid overdose and 1,101 had a BPA alert during March 2022, with 32.7% of BPA alerts resulting in naloxone prescribing. The most common reasons selected for not prescribing naloxone were "patient refusal" and "criteria not met." Only 354 patients (17.1%) at risk for opioid overdose also had a BPA alert. CONCLUSION: State legislation and implementation of the BPA significantly increased naloxone prescribing rates. However, a significant proportion of patients identified as being at risk did not have a BPA alert and most BPA alerts did not result in naloxone prescribing, suggesting a need for improvement of the BPA.

6.
J Hosp Palliat Care ; 27(2): 77-81, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38863562

RESUMO

This case report explores the challenges and complexities associated with opioid management of cancer pain, emphasizing the importance of early involvement of a hospice consultation team and the adoption of a multidisciplinary approach to care. A 56-year-old man with advanced pancreatic cancer experienced escalating pain and inappropriate opioid prescriptions, highlighting the shortcomings of traditional pain management approaches. Despite procedural intervention by the attending physician and increased opioid dosages, the patient's condition deteriorated. Subsequently, the involvement of a hospice consultation team, in conjunction with collaborative psychiatric care, led to an overall improvement. The case underscores the necessity of early hospice engagement, psychosocial assessments, and collaborative approaches in the optimization of patient-centered palliative care.

7.
Genes Brain Behav ; 23(3): e12906, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38861664

RESUMO

Motherhood is a costly life-history transition accompanied by behavioral and neural plasticity necessary for offspring care. Motherhood in the monogamous prairie vole is associated with decreased pair bond strength, suggesting a trade-off between parental investment and pair bond maintenance. Neural mechanisms governing pair bonds and maternal bonds overlap, creating possible competition between the two. We measured mRNA expression of genes encoding receptors for oxytocin (oxtr), dopamine (d1r and d2r), mu-opioids (oprm1a), and kappa-opioids (oprk1a) within three brain areas processing salience of sociosensory cues (anterior cingulate cortex; ACC), pair bonding (nucleus accumbens; NAc), and maternal care (medial preoptic area; MPOA). We compared gene expression differences between pair bonded prairie voles that were never pregnant, pregnant (~day 16 of pregnancy), and recent mothers (day 3 of lactation). We found greater gene expression in the NAc (oxtr, d2r, oprm1a, and oprk1a) and MPOA (oxtr, d1r, d2r, oprm1a, and oprk1a) following the transition to motherhood. Expression for all five genes in the ACC was greatest for females that had been bonded for longer. Gene expression within each region was highly correlated, indicating that oxytocin, dopamine, and opioids comprise a complimentary gene network for social signaling. ACC-NAc gene expression correlations indicated that being a mother (oxtr and d1r) or maintaining long-term pair bonds (oprm1a) relies on the coordination of different signaling systems within the same circuit. Our study suggests the maternal brain undergoes changes that prepare females to face the trade-off associated with increased emotional investment in offspring, while also maintaining a pair bond.


Assuntos
Arvicolinae , Comportamento Materno , Núcleo Accumbens , Ligação do Par , Receptores Opioides mu , Animais , Feminino , Arvicolinae/genética , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo , Comportamento Materno/fisiologia , Núcleo Accumbens/metabolismo , Gravidez , Receptores de Ocitocina/genética , Receptores de Ocitocina/metabolismo , Receptores Opioides kappa/genética , Receptores Opioides kappa/metabolismo , Giro do Cíngulo/metabolismo , Área Pré-Óptica/metabolismo , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/metabolismo
8.
Med Anthropol Q ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860724

RESUMO

This article examines how militarized regimes of narcotics and price control sustain unpalliated cancer pain in Pakistan. It shows how these regimes of control-reimagined as "regimes of pain"-render morphine, a cheap, effective opiate analgesic, scarce in hospitals. Meanwhile, heroin, morphine's illegal derivative, proliferates in illicit circuits. The article highlights a devastating consequence of the global wars against drugs and "terror": the consignment of cancer patients to agonizing end-of-life pain. Widening the analytic lens upon palliation beyond bodies and their clinical encounters, the article offers a geopolitics of palliation. It shows how narcovigilance targeting illicit drugs has the perverse effect of throttling morphine's licit supply. It shows further how unviably low price ceilings, purported to ensure a poor population's access to morphine, render it scarce on the official market. These mutually reinforcing regimes of control thus thwart their own purported objectives, consigning cancer patients to preventable, yet unpalliated, pain.

9.
Harm Reduct J ; 21(1): 103, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807226

RESUMO

BACKGROUND: People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary. METHODS: We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons. RESULTS: Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime. CONCLUSIONS: Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.


Assuntos
Análise Custo-Benefício , Overdose de Drogas , Naloxona , Antagonistas de Entorpecentes , Transtornos Relacionados ao Uso de Opioides , Humanos , Connecticut/epidemiologia , Naloxona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/mortalidade , Antagonistas de Entorpecentes/uso terapêutico , Overdose de Drogas/mortalidade , Overdose de Drogas/prevenção & controle , Overdose de Opiáceos/mortalidade , Overdose de Opiáceos/prevenção & controle , Redução do Dano , Adulto , Masculino , Anos de Vida Ajustados por Qualidade de Vida , Feminino , Prisioneiros/estatística & dados numéricos
10.
Trends Neurosci ; 47(6): 418-431, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38762362

RESUMO

Evidence of central nervous system (CNS) exogenous opioid effects in humans has been primarily gained through neuroimaging of three participant populations: individuals after acute opioid administration, those with opioid use disorder (OUD), and those with chronic pain receiving opioid therapy. In both the brain and spinal cord, opioids alter processes of pain, cognition, and reward. Opioid-related CNS effects may persist and accumulate with longer opioid use duration. Meanwhile, opioid-induced benefits versus risks to brain health remain unclear. This review article highlights recent accumulating evidence for how exogenous opioids impact the CNS in humans. While investigation of CNS opioid effects has remained largely disparate across contexts of opioid acute administration, OUD, and chronic pain opioid therapy, integration across these contexts may enable advancement toward effective interventions.


Assuntos
Analgésicos Opioides , Encéfalo , Dor Crônica , Neuroimagem , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/administração & dosagem , Dor Crônica/tratamento farmacológico , Dor Crônica/diagnóstico por imagem , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Neuroimagem/métodos , Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia
11.
Addict Biol ; 29(5): e13393, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38706098

RESUMO

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.


Assuntos
Objetivos , Morfina , Motivação , Recompensa , Síndrome de Abstinência a Substâncias , Animais , Síndrome de Abstinência a Substâncias/psicologia , Motivação/efeitos dos fármacos , Masculino , Morfina/farmacologia , Ratos , Dependência de Morfina/psicologia , Entorpecentes/farmacologia , Condicionamento Operante/efeitos dos fármacos
12.
Int J Drug Policy ; 128: 104462, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38795466

RESUMO

BACKGROUND: Expanding public naloxone access is a key strategy to reduce opioid overdose fatalities. We describe tailored community-engaged, data-driven approaches to install and maintain naloxone housing units (naloxone boxes) in New York State and estimate the cost of these approaches. METHODS: Guided by the Consolidated Framework for Implementation Research, we collected data from administrative records and key informant interviews that documented the unique processes employed by four counties enrolled in the HEALing Communities Study to install and maintain naloxone housing units. We conducted a prospective micro-costing analysis to estimate the cost of each naloxone housing unit strategy from the community perspective. RESULTS: While all counties used a coalition to guide action planning for naloxone distribution, we identified unique approaches to implementing naloxone housing units: 1) County-led with technology expansion; 2) County-led grassroots; 3) Small-scale rural opioid overdose prevention program (OOPP) contract and 4) Comprehensive OOPP contract including overdose education and naloxone distribution (OEND) to individuals. The first two county-led approaches had lower cost per naloxone dose disbursed ($28-$38) compared to outsourcing to an OOPP ($183-$266); costs depended on services added to installing and maintaining units, such as OEND. Barriers included competing demands on public health resources (i.e., COVID-19) and stigma toward naloxone and opioid use disorder. Geographic access was a barrier in rural areas whereas existing infrastructure was a facilitator in urban counties. The policy landscape in New York State, which provides free naloxone kits and financial support to OOPPs, facilitated implementation in all counties. CONCLUSIONS: If a community has the resources, installing and maintaining naloxone housing units in-house can be less expensive than contracting with an outside partner. However, contracts that include OEND may be more effective at reaching target populations. Financial support from health departments and legislative authorization are important facilitators to making naloxone available in public settings.


Assuntos
Naloxona , Antagonistas de Entorpecentes , Naloxona/administração & dosagem , Humanos , Antagonistas de Entorpecentes/administração & dosagem , New York , Overdose de Opiáceos/prevenção & controle , Overdose de Opiáceos/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Acessibilidade aos Serviços de Saúde , Estudos Prospectivos , Overdose de Drogas/prevenção & controle , Overdose de Drogas/tratamento farmacológico , Participação da Comunidade
13.
J Neural Transm (Vienna) ; 131(5): 563-580, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38570361

RESUMO

Over 50 million Americans endure chronic pain where many do not receive adequate treatment and self-medicate to manage their pain by taking substances like opioids and cannabis. Research has shown high comorbidity between chronic pain and substance use disorders (SUD) and these disorders share many common neurobiological underpinnings, including hypodopaminergic transmission. Drugs commonly used for self-medication such as opioids and cannabis relieve emotional, bothersome components of pain as well as negative emotional affect that perpetuates misuse and increases the risk of progressing towards drug abuse. However, the causal effect between chronic pain and the development of SUDs has not been clearly established. In this review, we discuss evidence that affirms the proposition that chronic pain is a risk factor for the development of opioid and cannabis use disorders by outlining the clinical evidence and detailing neurobiological mechanisms that link pain and drug misuse. Central to the link between chronic pain and opioid and cannabis misuse is hypodopaminergic transmission and the modulation of dopamine signaling in the mesolimbic pathway by opioids and cannabis. Moreover, we discuss the role of kappa opioid receptor activation and neuroinflammation in the context of dopamine transmission, their contribution to opioid and cannabis withdrawal, along with potential new treatments.


Assuntos
Analgésicos Opioides , Dor Crônica , Transtornos Relacionados ao Uso de Opioides , Humanos , Dor Crônica/tratamento farmacológico , Dor Crônica/fisiopatologia , Analgésicos Opioides/efeitos adversos , Animais , Abuso de Maconha/complicações , Abuso de Maconha/fisiopatologia
14.
J Chromatogr A ; 1725: 464875, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38678692

RESUMO

Ultrasonic-assisted dispersive micro solid phase extraction (UA-DMSPE) is proposed as a fast and easy technique for the extraction and preconcentration of methadone and tramadol from serum samples. Different sorbents including carbon nanotubes, oxidized carbon nanotubes, and TiO2 nanoparticles were compared to extract methadone and tramadol. The best performance was obtained using oxidized carbon nanotubes due to the strong affinity between the drugs and carbon nanotube adsorbents. Final analysis of drugs performed by using gas chromatography-mass spectrometric detection. Different parameters affecting the extraction efficiency, such as the sample volume, amount of adsorbent, desorption solvent type and volume, centrifugation time, and speed were investigated and optimized. The striking features of this technique are correlated to its speed and the small volumes of sample (about 1 mL), desorption solvent (about 50 µL), and adsorbent (about 0.001 g) for analysis of drugs, and finally, milder centrifugation conditions relative to the previously reported adsorbent. The optimal parameters were achieved as follows: pH value was set at 9, the sample volume was adjusted to 1200 µL, the amount of adsorbent used was 1 mg, the extraction time was set at 5 min, and the volume of the desorption solvent was adjusted to 50 µL. The limits of detections (0.5 and 0.8 ng mL-1) and quantifications (1.5 and 2.5 ng mL-1) were obtained for methadone and tramadol, respectively. The developed method also showed good repeatability, relative standard deviation (RSD) of 9.49 % and 7.47 % (n = 5), for the spiked aqueous solution at the concentration level of 10, 50, and 100 ng mL-1 for analytes, and linearity, R ≥ 0.9809. The results showed that UA-DMSPE is a quick, relatively inexpensive, and environmentally friendly alternative technique for the extraction of opiate drugs from serum samples.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Limite de Detecção , Metadona , Microextração em Fase Sólida , Tramadol , Tramadol/sangue , Metadona/sangue , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Microextração em Fase Sólida/métodos , Nanotubos de Carbono/química , Reprodutibilidade dos Testes , Adsorção , Titânio
15.
Sleep ; 47(5)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38447008

RESUMO

Dynorphin is an endogenous opiate localized in many brain regions and spinal cord, but the activity of dynorphin neurons during sleep is unknown. Dynorphin is an inhibitory neuropeptide that is coreleased with orexin, an excitatory neuropeptide. We used microendoscopy to test the hypothesis that, like orexin, the dynorphin neurons are wake-active. Dynorphin-cre mice (n = 3) were administered rAAV8-Ef1a-Con/Foff 2.0-GCaMP6M into the zona incerta-perifornical area, implanted with a GRIN lens (gradient reflective index), and electrodes to the skull that recorded sleep. One month later, a miniscope imaged calcium fluorescence in dynorphin neurons during multiple bouts of wake, non-rapid-eye movement (NREM), and rapid-eye movement (REM) sleep. Unbiased data analysis identified changes in calcium fluorescence in 64 dynorphin neurons. Most of the dynorphin neurons (72%) had the highest fluorescence during bouts of active and quiet waking compared to NREM or REM sleep; a subset (20%) were REM-max. Our results are consistent with the emerging evidence that the activity of orexin neurons can be classified as wake-max or REM-max. Since the two neuropeptides are coexpressed and coreleased, we suggest that dynorphin-cre-driven calcium sensors could increase understanding of the role of this endogenous opiate in pain and sleep.


Assuntos
Dinorfinas , Neurônios , Sono REM , Vigília , Zona Incerta , Animais , Camundongos , Dinorfinas/metabolismo , Dinorfinas/fisiologia , Neurônios/fisiologia , Orexinas/metabolismo , Orexinas/fisiologia , Sono REM/fisiologia , Vigília/fisiologia , Zona Incerta/fisiologia , Zona Incerta/fisiopatologia
17.
Ir J Med Sci ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502432

RESUMO

BACKGROUND: Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC. METHOD: Fifty-six MMT cases (< 75 mg/day methadone, > 3 months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4 mg/day) once a day for 2 weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks. RESULTS: The dose of 4 mg/day naloxone was excluded from the study due to severe OWS. The precipitants of groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2 mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (P = 0.0133), 0.5 mg/day dose only improved the stool consistency (P = 0.0016). The patients' CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2 mg/day groups, respectively, withdrew from the study due to OWS. CONCLUSION: Oral naloxone at doses of 0.5 and 2 mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4 mg induced intolerable OWS.

18.
Prehosp Disaster Med ; 39(2): 212-217, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38449098

RESUMO

OBJECTIVE: Opioid use disorder is a cause of significant morbidity and mortality. In order to reverse opioid overdose as quickly as possible, many institutions and municipalities have encouraged people with no professional medical training to carry and administer naloxone. This study sought to provide preliminary data for research into the rates of adverse effects of naloxone when administered by bystanders compared to Emergency Medical Services (EMS) personnel, since this question has not been studied previously. METHODS: This was a retrospective cohort study performed at an urban, tertiary, academic medical center that operates its own EMS service. A consecutive sample of patients presenting to EMS with opioid overdose requiring naloxone was separated into two groups based on whether naloxone was administered by bystanders or by EMS personnel. Each group was analyzed to determine the incidence of four pre-specified adverse events. RESULTS: There was no significant difference in the rate of adverse events between the bystander (19%) and EMS (16%) groups (OR = 1.23; 95% CI, 0.63 - 2.32; P = .499) in this small sample. Based on these initial results, a study would need a sample size of 6,188 in order to reach this conclusion with 80% power. Similarly, there were no significant differences in the rates of any of the individual adverse events. Secondary analysis of patients' demographics showed differences between the two groups which generate hypotheses for further investigation of disparities in naloxone administration. CONCLUSIONS: This preliminary study provides foundational data for further investigation of naloxone administration by bystanders. Adverse events after the prehospital administration of naloxone are rare, and future studies will require large sample sizes. These preliminary data did not demonstrate a statistically significant difference in adverse event rates when comparing naloxone administration by bystanders and EMS clinicians. This study provides data that will be useful for conducting further research on multiple facets of this topic.


Assuntos
Serviços Médicos de Emergência , Naloxona , Antagonistas de Entorpecentes , Humanos , Naloxona/administração & dosagem , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/uso terapêutico , Estudos Retrospectivos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Overdose de Drogas/tratamento farmacológico , Overdose de Opiáceos/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Estudos de Coortes
19.
Drug Alcohol Depend Rep ; 10: 100222, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38463634

RESUMO

Background: In March 2020, policy changes by the Substance Abuse and Mental Health Services Administration and the Drug Enforcement Administration aimed to maintain access to office-based opioid treatment services by easing telehealth buprenorphine prescribing restrictions. However, the effectiveness of these changes remains largely unmeasured. The objective of this study was to measure the effectiveness of COVID-19-related telehealth flexibilities in an all-payer cohort from the Texas Prescription Monitoring Program. Methods: Using Texas Prescription Monitoring Program data, we identified oral buprenorphine and buprenorphine/naloxone prescriptions dispensed in Texas between September 1, 2019, and September 26, 2020. Weekly counts of prescriptions, prescribing physicians, and dispensing pharmacies were analyzed. An autoregressive integrated moving average (ARIMA) model estimated changes in prescription volume between pre-implementation (September 1, 2019 - February 15, 2020) and post-implementation (April 12, 2020 - September 26, 2020) periods. Results: Pre-flexibility, an average of 8898 (SD: 342) buprenorphine prescriptions were dispensed to 7829 (SD: 326) patients weekly. This declined to 8360 (SD: 247) prescriptions and 7661 (SD: 229) patients post-flexibility. Adjusted for seasonality, this represented a statistically significant average decline of -257.27 (95% CI: -426.06, -88.49) patients and -647.01 (95% CI: -856.67, -437.36) prescriptions per week. Discussion: Our results suggest a modest decline in buprenorphine dispensing volume early in the COVID-19 pandemic. While difficult to assess its significance, it can be assumed that telehealth flexibilities mitigated a potentially larger decline. Future research should explore system and individual-level barriers to telehealth utilization.

20.
J Am Coll Emerg Physicians Open ; 5(2): e13134, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38464332

RESUMO

Recent increases in pediatric and adolescent opioid fatalities mandate an urgent need for early consideration of possible opioid exposure and specific diagnostic and management strategies and interventions tailored to these unique populations. In contrast to adults, pediatric methods of exposure include accidental ingestions, prescription misuse, and household exposure. Early recognition, appropriate diagnostic evaluation, along with specialized treatment for opioid toxicity in this demographic are discussed. A key focus is on Naloxone, an essential medication for opioid intoxication, addressing its unique challenges in pediatric use. Unique pediatric considerations include recognition of accidental ingestions in our youngest population, critical social aspects including home safety and intentional exposure, and harm reduction strategies, mainly through Naloxone distribution and education on safe medication practices. It calls for a multifaceted approach, including creating pediatric-specific guidelines, to combat the opioid crisis among children and to work to lower morbidity and mortality from opioid overdoses.

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